clonidine and Ache studies

Clonidine: An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.
clonidine (amino form) : A clonidine that is 4,5-dihydro-1H-imidazol-2-amine in which one of the amino hydrogens is replaced by a 2,6-dichlorophenyl group.

Research Excerpts

Excerpt	Relevance	Reference
"Background and Purpose- Intrathecal baclofen (ITB) is an effective treatment for managing patients with severe poststroke spasticity, who can experience continued pain and decline in their quality of life (QoL)."	9.27	Effect of Intrathecal Baclofen on Pain and Quality of Life in Poststroke Spasticity. ( Abouihia, A; Calabrese, A; Cloud, G; Creamer, M; Francisco, GE; Kossmehl, P; Saltuari, L; Ward, AB; Wissel, J; Yochelson, M; Zampolini, M, 2018)
"This double-blind randomized controlled study was designed to evaluate the analgesic effects of topical treatments with clonidine (CLON) and pentoxifylline (PTX) tested alone or as low- and high-dose combinations in a human experimental model of pain."	9.22	Effects of topical combinations of clonidine and pentoxifylline on capsaicin-induced allodynia and postcapsaicin tourniquet-induced pain in healthy volunteers: a double-blind, randomized, controlled study. ( Bennett, GJ; Bley, K; Coderre, TJ; Gandhi, W; Laferrière, A; Ragavendran, JV; Schweinhardt, P; Ware, MA, 2016)
"We investigated pain evoked activity in the human secondary sensory cortex (SII) following clonidine administration in six healthy volunteers using multi-channel magnetoencephalography (MEG)."	9.12	Clonidine effects on pain evoked SII activity in humans. ( Bischoff, P; Bromm, B; Hauck, M; Lorenz, J; Morrow, TJ; Schmidt, G; Zimmermann, R, 2006)
"To evaluate the effects of clonidine and ephedrine on propofol-induced pain and on hemodynamic changes during the induction sequence."	9.12	Clonidine-ephedrine combination reduces pain on injection of propofol and blunts hemodynamic stress responses during the induction sequence. ( Fukushima, H; Furuya, A; Ishiyama, T; Kashimoto, S; Kumazawa, T; Oguchi, T, 2006)
"Clonidine premedication prevents tourniquet pain and reduces sympathetic nerve activity."	9.11	Oral clonidine premedication exacerbates hypotension following tourniquet deflation by inhibiting noradrenaline release. ( Hongo, T; Kim, C; Kobayashi, N; Maruyama, K; Ogawa, R; Takeda, S, 2004)
"It was possible to reduce the infiltration pain of local anesthetic during epidural catheterization by oral administration of 3 mg of tizanidine as premedication."	9.11	Effect of oral tizanidine on local-anesthetic infiltration pain during epidural catheterization. ( Imanaga, K; Inoue, T; Ogawa, R; Wajima, Z, 2004)
"Clonidine is frequently added to opioids in implantable intrathecal pumps for the management of chronic pain."	9.11	Stability of clonidine in clonidine-hydromorphone mixture from implanted intrathecal infusion pumps in chronic pain patients. ( Dunn, E; McCartney, C; Peng, P; Rudich, Z, 2004)
"To evaluate the effectiveness of intrathecal clonidine or clonidine/opioid admixture for the treatment of chronic pain states, a retrospective chart audit of 15 patients seen by the Pain Medicine and Neurosurgical Services was performed."	9.10	Long-term outcomes during treatment of chronic pain with intrathecal clonidine or clonidine/opioid combinations. ( Ackerman, LL; Follett, KA; Rosenquist, RW, 2003)
"Clonidine is approved in the US for epidural administration in the treatment of intractable neuropathic cancer pain, but is also administered intrathecally for this indication and both epidurally and intrathecally in the treatment of acute, postoperative pain."	9.09	Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-induced allodynia. ( Curry, R; Eisenach, JC; Hood, DD, 2000)
"We performed a double-blinded, randomized, controlled trial in 15 patients to determine the efficacy of intrathecal morphine or clonidine, alone or combined, in the treatment of neuropathic pain after spinal cord injury."	9.09	The efficacy of intrathecal morphine and clonidine in the treatment of pain after spinal cord injury. ( Cousins, MJ; Mather, LE; Molloy, AR; Rutkowski, SB; Siddall, PJ; Walker, S, 2000)
" Treatment with tizanidine resulted in a significant improvement in pain intensity (P=0."	9.09	Open-label dose-titration safety and efficacy study of tizanidine hydrochloride in the treatment of spasticity associated with chronic stroke. ( Dromerick, A; Gelber, DA; Good, DC; Richardson, M; Sergay, S, 2001)
"We examined the analgesic effects of orally administered clonidine on pain induced by injection of propofol (Diprivan; 2,6-diisopropyl phenol)."	9.09	Orally administered clonidine significantly reduces pain during injection of propofol. ( Inoue, T; Ogawa, R; Ogura, A; Wajima, Z; Yoshikawa, T, 2001)
"Twenty patients with chronic pain who previously had obtained analgesia from epidural clonidine and lignocaine agreed to participate in a double-blind crossover study of lumbar epidural clonidine (150 micrograms), lignocaine (40 mg) and the combination of clonidine (150 microgram) and lignocaine (40 mg), all drugs were given in a volume of 3 ml."	9.08	A double-blind randomised comparison of the effects of epidural clonidine, lignocaine and the combination of clonidine and lignocaine in patients with chronic pain. ( Glynn, C; O'Sullivan, K, 1996)
" Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve."	9.08	Epidural epinephrine and clonidine: segmental analgesia and effects on different pain modalities. ( Arendt-Nielsen, L; Curatolo, M; Petersen-Felix, S; Zbinden, AM, 1997)
"Clonidine is approved for intraspinal administration in the treatment of neuropathic cancer pain."	9.08	Intrathecal, but not intravenous, clonidine reduces experimental thermal or capsaicin-induced pain and hyperalgesia in normal volunteers. ( Curry, R; Eisenach, JC; Hood, DD, 1998)
"Clonidine, but not placebo, caused pain relief, sedation, and decreased blood pressure and heart rate after bolus epidural injection."	9.07	Epidural clonidine treatment for refractory reflex sympathetic dystrophy. ( Eisenach, JC; Jackson, K; Rauck, RL; Southern, J; Young, LD, 1993)
"In a randomized, double-blind, 2-period crossover study, 24 patients with pain due to diabetic polyneuropathy received transdermal clonidine, 0."	9.07	Transdermal clonidine versus placebo in painful diabetic neuropathy. ( Benjamin, J; Lynch, SA; Max, MB; Muir, J; Zeigler, D, 1992)
"In order to assess the effect of spinal clonidine on tourniquet pain, 30 patients scheduled to undergo orthopaedic surgery under spinal anaesthesia were allocated randomly to two groups."	9.06	Prevention of tourniquet pain by spinal isobaric bupivacaine with clonidine. ( Belon, M; Boico, O; Bonnet, F; Diallo, A; Guilbaud, M; Saada, M, 1989)
"In a randomised double-blind study of 20 patients with chronic pain, epidural morphine 5 mg in 5 ml of saline was compared with epidural clonidine 150 micrograms in 5 ml of saline."	9.06	A double-blind comparison between epidural morphine and epidural clonidine in patients with chronic non-cancer pain. ( Dawson, D; Glynn, C; Sanders, R, 1988)
"Despite weak evidence, clonidine may be a useful adjunct in epidural or spinal morphine therapy of cancer pain."	8.84	[Clonidine in the treatment of cancer pain]. ( Nielsen, JB; Sjøgren, P, 2008)
"Sprague-Dawley rats were used to test the analgesic effect of pentazocine and neostigmine using the paw formalin pain model and the incision mechanical allodynia model."	8.12	Antinociceptive Effects and Interaction Mechanisms of Intrathecal Pentazocine and Neostigmine in Two Different Pain Models in Rats. ( Bai, X; Guo, J; Huang, H; Ouyang, H; Wu, S; Zhang, K, 2022)
"Clonidine was successful in reducing pain related distress and facilitating adherence to the penicillin regimen."	7.96	Clonidine for pain-related distress in Aboriginal children on a penicillin regimen to prevent recurrence of rheumatic fever. ( Atkinson, N; Cook, J; Kelly, J; Mitchell, A; Ralph, AP; Remenyi, B; Spain, B; Wade, V, 2020)
"Our data indicate that IV dexmedetomidine exerts pronounced antinociception against CRD-induced visceral pain and suggest that the antinociceptive effect of dexmedotimidine is mediated in part by opioid receptors, but peripheral alpha(2)-ARs are not involved."	7.75	The antinociceptive effects of intravenous dexmedetomidine in colorectal distension-induced visceral pain in rats: the role of opioid receptors. ( Bilge, SS; Bostanci, MO; Bozkurt, A; Ciftcioglu, E; Dilek, A; Güldogus, F; Ilkaya, F; Ulger, F, 2009)
"To investigate the effects of intrathecal escin and clonidine, used alone or in combination, in the treatment of neuropathic pain in rats and the possible mechanism."	7.75	[Effects of intrathecal escin and clonidine in the treatment of neuropathic pain in rats]. ( Chen, CY; Huang, Y; Qing, ZH; Wang, B; Yao, XH; Zhou, P, 2009)
" For their positive morphine analgesia modulation (due to alpha(2C)-AR stimulation) and sedation overcoming (due to alpha(2A)-AR antagonism), 8 and 11 might be useful as adjuvant agents in the management of pain with morphine."	7.75	Might adrenergic alpha2C-agonists/alpha2A-antagonists become novel therapeutic tools for pain treatment with morphine? ( Bruzzone, A; Cardinaletti, C; Del Bello, F; Ghelfi, F; Giannella, M; Mattioli, L; Paris, H; Perfumi, M; Piergentili, A; Pigini, M; Quaglia, W, 2009)
"To investigate the effects of intrathecal ouabain and tizanidine injection for treatment of neuropathic pain in rats."	7.74	[Effects of intrathecal ouabain and tizanidine injection for treatment of neuropathic pain in rats]. ( He, WX; Li, Q; Lin, LL; Liu, XG; Ou-Yang, HD; Wang, PZ; Zeng, WA; Zhang, ZQ, 2008)
"Clonidine can effectively reduce pain and/or hypersensitivity."	7.74	Effects of topical application of clonidine cream on pain behaviors and spinal Fos protein expression in rat models of neuropathic pain, postoperative pain, and inflammatory pain. ( Arita, H; Hanaoka, K; Hayashida, M; Li, C; Sawamura, S; Sekiyama, H; Sumida, T; Takeda, K; Yamada, Y, 2007)
"We studied whether peripheral alpha2-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha2-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)-adrenoceptor antagonist), MK-912 (selective alpha2C-adrenoceptor antagonist), and clonidine (alpha2-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain."	7.74	The involvement of peripheral alpha 2-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain. ( Bosković, B; Paranos, SLj; Prostran, MS; Stepanović-Petrović, RM; Tomić, MA; Ugresić, ND; Vucković, SM, 2007)
"These data indicate for the first time that the clonidine-induced increase in punctuate mechanical threshold is mediated via the activation of all but M2 muscarinic receptor subtypes, and via the activation of alpha4beta2 but not alpha7 nicotinic receptor subtypes in a rodent model for human postoperative pain."	7.73	Spinal muscarinic and nicotinic subtypes activated by clonidine in postincisional pain. ( Boselli, E; Chassard, D; Duflo, F; Ryvlin, P, 2005)
"Intrathecal clonidine reduces tactile allodynia in animal models of neuropathic pain, and this effect is blocked by atropine."	7.72	Plasticity in action of intrathecal clonidine to mechanical but not thermal nociception after peripheral nerve injury. ( Conklin, D; Eisenach, JC; Paqueron, X, 2003)
"We investigated the interaction between spinally administered bupivacaine and clonidine using an animal model of acute and inflammatory pain."	7.72	Intrathecal clonidine and bupivacaine have synergistic analgesia for acute thermally or inflammatory-induced pain in rats. ( Hanaoka, K; Nishiyama, T, 2004)
"Intrathecally administered alpha2-adrenergic receptor subtype-specific antagonists were used to determine which alpha2-adrenergic receptor subtype mediates the analgesic effect of intrathecally administered tizanidine in a chronic constriction injury (CCI) rat model of neuropathic pain."	7.72	Alpha2-adrenergic receptor subtype specificity of intrathecally administered tizanidine used for analgesia for neuropathic pain. ( Dills, CV; Leiphart, JW; Levy, RM, 2004)
"To report a case of possible clonidine-induced hypertension (by Naranjo score) in a patient with a C4 spinal lesion."	7.71	Clonidine-induced hypertension in a patient with a spinal lesion. ( Backo, AL; Clause, SL; Gibbs, KA; Triller, DM, 2002)
"Spinally-administered midazolam, a benzodiazepine, and clonidine, an alpha2-adrenergic receptor agonist, have significant synergistic effects on thermally-induced acute and formalin-induced inflammatory pain."	7.71	The synergistic interaction between midazolam and clonidine in spinally-mediated analgesia in two different pain models of rats. ( Hanaoka, K; Nishiyama, T, 2001)
"Intrathecal administration of alpha(2) adrenergic agonists, such as clonidine, is capable of alleviating neuropathic pain."	7.70	Role of spinal muscarinic and nicotinic receptors in clonidine-induced nitric oxide release in a rat model of neuropathic pain. ( Chen, SR; Eisenach, J; Pan, HL; Xu, Z, 2000)
" We describe a case of chronic pain following SCI which failed to respond to a variety of approaches including intrathecal administration of morphine."	7.69	Intrathecal morphine and clonidine in the management of spinal cord injury pain: a case report. ( Cousins, MJ; Gray, M; Rutkowski, S; Siddall, PJ, 1994)
"The aim of the present study was to investigate whether clonidine and morphine interact positively to produce analgesia against the low intensity tonic pain represented by the formalin model in rats."	7.69	Morphine, clonidine coadministration in subanalgesic doses: effective control of tonic pain. ( Gurtu, S; Mukerjee, D; Shukla, S, 1994)
"To assess the benefit of ketamine addition to a morphine-clonidine-lidocaine mixture administered continuously by the intrathecal route for the treatment of cancer pain."	7.69	[Cancer pain: beneficial effect of ketamine addition to spinal administration of morphine-clonidine-lidocaine mixture]. ( Lemos, D; Muller, A, 1996)
"The effect of intrathecal morphine (MO) and the alpha 2-adrenoceptor agonists clonidine (CLON) and dexmedetomidine on self-mutilation (autotomy), a behavior that may indicate the presence of neuropathic pain, has been examined in rats."	7.68	The differential effects of morphine and the alpha 2-adrenoceptor agonists clonidine and dexmedetomidine on the prevention and treatment of experimental neuropathic pain. ( Puke, MJ; Wiesenfeld-Hallin, Z, 1993)
"Clonidine was administered by epidural injections with per os relay and long term therapeutic follow-up to 38 patients with deafferentation neurological sequellar pain either fully or partly intractable to classical pain treatments."	7.67	[Thoracolumbar or sacral epidural administration of clonidine in deafferentation pain: possibilities, limits and long-term follow-up]. ( Farcot, JM; Grasser, C; Mercky, F, 1989)
"A case is reported in which spinal intrathecal administration of clonidine produced pain."	7.67	Pain after spinal intrathecal clonidine. An adverse interaction with tricyclic antidepressants? ( Hardy, PA; Wells, JC, 1988)
"The use of clonidine in the management of opiate abstinence is presented in a patient dependent upon levorphanol tartrate given for chronic pain."	7.66	The use of clonidine for management of opiate abstinence in a chronic pain patient. ( Bakris, GL; Cross, PD; Hammarsten, JE, 1982)
"Pain was not different in the two groups after tourniquet release."	6.69	Adding clonidine to lidocaine for intravenous regional anesthesia prevents tourniquet pain. ( Bernard, JM; Bonnet, F; Gentili, M, 1999)
"Tizanidine is a well-tolerated and effective drug for symptomatic treatment of spasticity."	6.67	A double-blind, placebo-controlled trial of tizanidine in the treatment of spasticity caused by multiple sclerosis. United Kingdom Tizanidine Trial Group. ( , 1994)
"Clonidine is an agonist at the alpha2-adrenergic receptor that has been in clinical use for over 40 years."	6.47	Clonidine: clinical pharmacology and therapeutic use in pain management. ( Neil, MJ, 2011)
" Compared with midazolam, dexmedetomidine was favorable in reducing both emergence delirium and pain in the postoperative care unit, and both clonidine and dexmedetomidine reduced anxiety in the postoperative care unit."	5.69	Postoperative recovery in preschool-aged children: A secondary analysis of a randomized controlled trial comparing premedication with midazolam, clonidine, and dexmedetomidine. ( Bromfalk, Å; Engström, Å; Hultin, M; Myrberg, T; Walldén, J, 2023)
" In the mouse formalin test, DBV injection produced a dramatic leftward shift in the dose-response curve for clonidine-induced analgesia."	5.35	Acupoint stimulation with diluted bee venom (apipuncture) potentiates the analgesic effect of intrathecal clonidine in the rodent formalin test and in a neuropathic pain model. ( Beitz, AJ; Han, HJ; Kim, HW; Kwon, YB; Lee, HJ; Lee, JH; Roh, DH; Seo, HS; Yoon, SY, 2009)
"The clonidine response was inhibited by yohimbine (0."	5.32	Clonidine and guanfacine-induced antinociception in visceral pain: possible role of alpha 2/I2 binding sites. ( Hosseini, AR; Khansefid, N; Sabetkasaie, M; Sadat Ladgevardi, MA; Vala, S, 2004)
"CFA injection resulted in significant thermal hyperalgesia throughout the four days of observation."	5.31	Intrathecal clonidine decreases spinal nitric oxide release in a rat model of complete Freund's adjuvant induced inflammatory pain. ( Cheng, JT; Chuang, YC; Lin, CR; Wang, CJ; Yang, LC, 2002)
"Clonidine was found to be highly effective in arthritic animals, even at the lower concentration: the elevation in threshold produced by 30 micrograms/kg i."	5.28	Potent antinociceptive effects of clonidine systemically administered in an experimental model of clinical pain, the arthritic rat. ( Besson, JM; Guilbaud, G; Kayser, V, 1992)
"Evidence suggests that the pain and hyperalgesia in SMP are related to activation of peripheral adrenergic receptors."	5.28	Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain. ( Campbell, JN; Davis, KD; Meyer, RA; Raja, SN; Treede, RD, 1991)
"Background and Purpose- Intrathecal baclofen (ITB) is an effective treatment for managing patients with severe poststroke spasticity, who can experience continued pain and decline in their quality of life (QoL)."	5.27	Effect of Intrathecal Baclofen on Pain and Quality of Life in Poststroke Spasticity. ( Abouihia, A; Calabrese, A; Cloud, G; Creamer, M; Francisco, GE; Kossmehl, P; Saltuari, L; Ward, AB; Wissel, J; Yochelson, M; Zampolini, M, 2018)
"Clonidine therapy was used to alleviate symptoms of narcotic analgesic withdrawal."	5.27	Narcotic bowel syndrome treated with clonidine. Resolution of abdominal pain and intestinal pseudo-obstruction. ( Greenberger, NJ; McPhee, MS; Sandgren, JE, 1984)
"This double-blind randomized controlled study was designed to evaluate the analgesic effects of topical treatments with clonidine (CLON) and pentoxifylline (PTX) tested alone or as low- and high-dose combinations in a human experimental model of pain."	5.22	Effects of topical combinations of clonidine and pentoxifylline on capsaicin-induced allodynia and postcapsaicin tourniquet-induced pain in healthy volunteers: a double-blind, randomized, controlled study. ( Bennett, GJ; Bley, K; Coderre, TJ; Gandhi, W; Laferrière, A; Ragavendran, JV; Schweinhardt, P; Ware, MA, 2016)
"After 50 µg clonidine or 5 mg bupivacaine, the heat pain tolerance increased by ∼1°C, similar to the analgesic effect of 5 mg epidural morphine or 30 µg epidural fentanyl in previous studies using this experimental heat pain model."	5.17	Analgesic and sympatholytic effects of low-dose intrathecal clonidine compared with bupivacaine: a dose-response study in female volunteers. ( Angst, MS; Ginosar, Y; Riley, ET, 2013)
" However, the incidence of nocturnal enuresis, urgency attacks, and daytime incontinence were significantly reduced compared with baseline in the tizanidine group (P=."	5.16	Doxazosin versus tizanidine for treatment of dysfunctional voiding in children: a prospective randomized open-labeled trial. ( Dawaba, M; El-Assmy, MM; El-Hefnawy, AS; Hafez, AT; Helmy, T; Sarhan, O, 2012)
"We investigated pain evoked activity in the human secondary sensory cortex (SII) following clonidine administration in six healthy volunteers using multi-channel magnetoencephalography (MEG)."	5.12	Clonidine effects on pain evoked SII activity in humans. ( Bischoff, P; Bromm, B; Hauck, M; Lorenz, J; Morrow, TJ; Schmidt, G; Zimmermann, R, 2006)
"To evaluate the effects of clonidine and ephedrine on propofol-induced pain and on hemodynamic changes during the induction sequence."	5.12	Clonidine-ephedrine combination reduces pain on injection of propofol and blunts hemodynamic stress responses during the induction sequence. ( Fukushima, H; Furuya, A; Ishiyama, T; Kashimoto, S; Kumazawa, T; Oguchi, T, 2006)
"The addition of clonidine to local anaesthetics enhances pain relief after peripheral nerve block, but the site of action is unproven."	5.11	Clonidine added to bupivacaine enhances and prolongs analgesia after brachial plexus block via a local mechanism in healthy volunteers. ( Eichler, HG; Fleck, T; Hutschala, D; Klimscha, W; Mascher, H; Schmetterer, L; Tschernko, EM, 2004)
"Clonidine premedication prevents tourniquet pain and reduces sympathetic nerve activity."	5.11	Oral clonidine premedication exacerbates hypotension following tourniquet deflation by inhibiting noradrenaline release. ( Hongo, T; Kim, C; Kobayashi, N; Maruyama, K; Ogawa, R; Takeda, S, 2004)
"It was possible to reduce the infiltration pain of local anesthetic during epidural catheterization by oral administration of 3 mg of tizanidine as premedication."	5.11	Effect of oral tizanidine on local-anesthetic infiltration pain during epidural catheterization. ( Imanaga, K; Inoue, T; Ogawa, R; Wajima, Z, 2004)
"Clonidine is frequently added to opioids in implantable intrathecal pumps for the management of chronic pain."	5.11	Stability of clonidine in clonidine-hydromorphone mixture from implanted intrathecal infusion pumps in chronic pain patients. ( Dunn, E; McCartney, C; Peng, P; Rudich, Z, 2004)
"To evaluate the effectiveness of intrathecal clonidine or clonidine/opioid admixture for the treatment of chronic pain states, a retrospective chart audit of 15 patients seen by the Pain Medicine and Neurosurgical Services was performed."	5.10	Long-term outcomes during treatment of chronic pain with intrathecal clonidine or clonidine/opioid combinations. ( Ackerman, LL; Follett, KA; Rosenquist, RW, 2003)
"Clonidine is approved in the US for epidural administration in the treatment of intractable neuropathic cancer pain, but is also administered intrathecally for this indication and both epidurally and intrathecally in the treatment of acute, postoperative pain."	5.09	Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-induced allodynia. ( Curry, R; Eisenach, JC; Hood, DD, 2000)
"We performed a double-blinded, randomized, controlled trial in 15 patients to determine the efficacy of intrathecal morphine or clonidine, alone or combined, in the treatment of neuropathic pain after spinal cord injury."	5.09	The efficacy of intrathecal morphine and clonidine in the treatment of pain after spinal cord injury. ( Cousins, MJ; Mather, LE; Molloy, AR; Rutkowski, SB; Siddall, PJ; Walker, S, 2000)
" Treatment with tizanidine resulted in a significant improvement in pain intensity (P=0."	5.09	Open-label dose-titration safety and efficacy study of tizanidine hydrochloride in the treatment of spasticity associated with chronic stroke. ( Dromerick, A; Gelber, DA; Good, DC; Richardson, M; Sergay, S, 2001)
"We examined the analgesic effects of orally administered clonidine on pain induced by injection of propofol (Diprivan; 2,6-diisopropyl phenol)."	5.09	Orally administered clonidine significantly reduces pain during injection of propofol. ( Inoue, T; Ogawa, R; Ogura, A; Wajima, Z; Yoshikawa, T, 2001)
"Twenty patients with chronic pain who previously had obtained analgesia from epidural clonidine and lignocaine agreed to participate in a double-blind crossover study of lumbar epidural clonidine (150 micrograms), lignocaine (40 mg) and the combination of clonidine (150 microgram) and lignocaine (40 mg), all drugs were given in a volume of 3 ml."	5.08	A double-blind randomised comparison of the effects of epidural clonidine, lignocaine and the combination of clonidine and lignocaine in patients with chronic pain. ( Glynn, C; O'Sullivan, K, 1996)
"We investigated the influence of preanesthetic medication on the pain relieving effect of the lidocaine tape during needle insertion for venous cannulation."	5.08	[Influence of preanesthetic medication on the effect of a local anesthetic tape]. ( Horikawa, Y; Kagawa, T; Kondo, M; Obara, H; Ohnishi, H, 1997)
" Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve."	5.08	Epidural epinephrine and clonidine: segmental analgesia and effects on different pain modalities. ( Arendt-Nielsen, L; Curatolo, M; Petersen-Felix, S; Zbinden, AM, 1997)
"Clonidine is approved for intraspinal administration in the treatment of neuropathic cancer pain."	5.08	Intrathecal, but not intravenous, clonidine reduces experimental thermal or capsaicin-induced pain and hyperalgesia in normal volunteers. ( Curry, R; Eisenach, JC; Hood, DD, 1998)
"Clonidine, but not placebo, caused pain relief, sedation, and decreased blood pressure and heart rate after bolus epidural injection."	5.07	Epidural clonidine treatment for refractory reflex sympathetic dystrophy. ( Eisenach, JC; Jackson, K; Rauck, RL; Southern, J; Young, LD, 1993)
"In a randomized, double-blind, 2-period crossover study, 24 patients with pain due to diabetic polyneuropathy received transdermal clonidine, 0."	5.07	Transdermal clonidine versus placebo in painful diabetic neuropathy. ( Benjamin, J; Lynch, SA; Max, MB; Muir, J; Zeigler, D, 1992)
"In order to assess the effect of spinal clonidine on tourniquet pain, 30 patients scheduled to undergo orthopaedic surgery under spinal anaesthesia were allocated randomly to two groups."	5.06	Prevention of tourniquet pain by spinal isobaric bupivacaine with clonidine. ( Belon, M; Boico, O; Bonnet, F; Diallo, A; Guilbaud, M; Saada, M, 1989)
"In a randomised double-blind study of 20 patients with chronic pain, epidural morphine 5 mg in 5 ml of saline was compared with epidural clonidine 150 micrograms in 5 ml of saline."	5.06	A double-blind comparison between epidural morphine and epidural clonidine in patients with chronic non-cancer pain. ( Dawson, D; Glynn, C; Sanders, R, 1988)
"Ziconotide is a nonopioid intrathecal analgesic used to manage moderate to severe chronic pain."	4.86	Ziconotide combination intrathecal therapy: rationale and evidence. ( Deer, T; Rauck, RL; Wallace, MS, 2010)
"Multimodal therapy encompasses a wide range of procedures and medications, including regional analgesia with continuous epidural or peripheral nerve block infusions, judicious opioids, acetaminophen, anti-inflammatory agents, anticonvulsants, ketamine, clonidine, mexiletine, antidepressants, and anxiolytics as options to treat or modulate pain at various sites of action."	4.84	The evolution of pain management in the critically ill trauma patient: Emerging concepts from the global war on terrorism. ( Black, IH; Malchow, RJ, 2008)
"Despite weak evidence, clonidine may be a useful adjunct in epidural or spinal morphine therapy of cancer pain."	4.84	[Clonidine in the treatment of cancer pain]. ( Nielsen, JB; Sjøgren, P, 2008)
" Opioids are used in routinely, but alpha2-agonists, such as clonidine or cholinesterase inhibitors (neostigmine), have also been used for labour analgesia or to relieve pain following caesarean section."	4.83	The use of neuraxial adjuvant drugs (neostigmine, clonidine) in obstetrics. ( Roelants, F, 2006)
"This review has covered the five potential causes for opioid poorly responsive pain, namely (a) a loss of opioid receptors on the spinal terminals of C-fibres as a result of peripheral nerve damage, (b) an accumulation of morphine-3-glucuronide, (c) changes in the non-opioid peptides, F8Fa or CCK, either spinally or supraspinally, (d) actions of the opioid peptide dynorphin and (e) spinally generated hypersensitive states via activation of the NMDA receptor."	4.79	Neurophysiology of opioid poorly responsive pain. ( Dickenson, AH, 1994)
"The paper considers mechanisms of action and clinical efficacy of the drug sirdalud (tizanidine) in painful musculotonic syndromes."	4.79	[The use of sirdalud in painful muscle tonic syndromes]. ( Damulin, IV, 1997)
"To evaluate the duration and effect of superior hypogastric nerve block (SHNB) with ropivacaine and clonidine on postinterventional pain levels and opioid requirements in patients undergoing uterine artery embolization."	4.31	Postinterventional Patient Comfort After Uterine Artery Embolization and Superior Hypogastric Nerve Block. ( Binkert, CA; Najafi, A; Steffen, DA, 2023)
"Based on the potency ratios of clonidine and dexmedetomidine (8 to 1) we hypothesize that a lower dexmedetomidine dose would provide patients with 50 min of pain free tourniquet time."	4.12	A sequential allocation study to determine the ED ( Al Assadi, S; Kanazi, G; Karam, C; Zeeni, C, 2022)
"Sprague-Dawley rats were used to test the analgesic effect of pentazocine and neostigmine using the paw formalin pain model and the incision mechanical allodynia model."	4.12	Antinociceptive Effects and Interaction Mechanisms of Intrathecal Pentazocine and Neostigmine in Two Different Pain Models in Rats. ( Bai, X; Guo, J; Huang, H; Ouyang, H; Wu, S; Zhang, K, 2022)
"Clonidine was successful in reducing pain related distress and facilitating adherence to the penicillin regimen."	3.96	Clonidine for pain-related distress in Aboriginal children on a penicillin regimen to prevent recurrence of rheumatic fever. ( Atkinson, N; Cook, J; Kelly, J; Mitchell, A; Ralph, AP; Remenyi, B; Spain, B; Wade, V, 2020)
" In the present study, we examined whether dexmedetomidine and clonidine could inhibit the function of tetrodotoxin-sensitive Na(+) channels, which play important roles in the generation of pain."	3.77	Dexmedetomidine and clonidine inhibit the function of Na(v)1.7 independent of α(2)-adrenoceptor in adrenal chromaffin cells. ( Kanai, T; Maruta, T; Nemoto, T; Satoh, S; Tsuneyoshi, I; Wada, A; Yanagita, T, 2011)
"Our data indicate that IV dexmedetomidine exerts pronounced antinociception against CRD-induced visceral pain and suggest that the antinociceptive effect of dexmedotimidine is mediated in part by opioid receptors, but peripheral alpha(2)-ARs are not involved."	3.75	The antinociceptive effects of intravenous dexmedetomidine in colorectal distension-induced visceral pain in rats: the role of opioid receptors. ( Bilge, SS; Bostanci, MO; Bozkurt, A; Ciftcioglu, E; Dilek, A; Güldogus, F; Ilkaya, F; Ulger, F, 2009)
"To investigate the effects of intrathecal escin and clonidine, used alone or in combination, in the treatment of neuropathic pain in rats and the possible mechanism."	3.75	[Effects of intrathecal escin and clonidine in the treatment of neuropathic pain in rats]. ( Chen, CY; Huang, Y; Qing, ZH; Wang, B; Yao, XH; Zhou, P, 2009)
" For their positive morphine analgesia modulation (due to alpha(2C)-AR stimulation) and sedation overcoming (due to alpha(2A)-AR antagonism), 8 and 11 might be useful as adjuvant agents in the management of pain with morphine."	3.75	Might adrenergic alpha2C-agonists/alpha2A-antagonists become novel therapeutic tools for pain treatment with morphine? ( Bruzzone, A; Cardinaletti, C; Del Bello, F; Ghelfi, F; Giannella, M; Mattioli, L; Paris, H; Perfumi, M; Piergentili, A; Pigini, M; Quaglia, W, 2009)
"To investigate the effects of intrathecal ouabain and tizanidine injection for treatment of neuropathic pain in rats."	3.74	[Effects of intrathecal ouabain and tizanidine injection for treatment of neuropathic pain in rats]. ( He, WX; Li, Q; Lin, LL; Liu, XG; Ou-Yang, HD; Wang, PZ; Zeng, WA; Zhang, ZQ, 2008)
" The three models were benchmarked using compounds known to be active in neuropathic pain patients and nerve injury animal models, including gabapentin, amitriptyline and clonidine."	3.74	Transient allodynia pain models in mice for early assessment of analgesic activity. ( Cheevers, CV; Donello, JE; Gil, DW, 2008)
"Clonidine can effectively reduce pain and/or hypersensitivity."	3.74	Effects of topical application of clonidine cream on pain behaviors and spinal Fos protein expression in rat models of neuropathic pain, postoperative pain, and inflammatory pain. ( Arita, H; Hanaoka, K; Hayashida, M; Li, C; Sawamura, S; Sekiyama, H; Sumida, T; Takeda, K; Yamada, Y, 2007)
"We studied whether peripheral alpha2-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha2-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)-adrenoceptor antagonist), MK-912 (selective alpha2C-adrenoceptor antagonist), and clonidine (alpha2-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain."	3.74	The involvement of peripheral alpha 2-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain. ( Bosković, B; Paranos, SLj; Prostran, MS; Stepanović-Petrović, RM; Tomić, MA; Ugresić, ND; Vucković, SM, 2007)
"The chronic pain relieving effects following spinal administration of clonidine are probably connected to alpha2-adrenoreceptor-induced augmented synthesis of nitric oxide (NO) in the spinal cord."	3.73	Involvement of nitric oxide in clonidine-induced spinal analgesia. ( Aronov, S; Ben-Abraham, R; Givati-Divshi, D; Katz, Y, 2005)
"These data indicate for the first time that the clonidine-induced increase in punctuate mechanical threshold is mediated via the activation of all but M2 muscarinic receptor subtypes, and via the activation of alpha4beta2 but not alpha7 nicotinic receptor subtypes in a rodent model for human postoperative pain."	3.73	Spinal muscarinic and nicotinic subtypes activated by clonidine in postincisional pain. ( Boselli, E; Chassard, D; Duflo, F; Ryvlin, P, 2005)
" Compared with female WT mice, male WT mice exhibited higher pain thresholds and enhanced opioid (morphine) and alpha(2)-adrenergic (clonidine) receptor-induced antinociception in a spinal reflex test."	3.72	Contribution of GIRK2-mediated postsynaptic signaling to opiate and alpha 2-adrenergic analgesia and analgesic sex differences. ( Bader, S; Basbaum, AI; Jan, LY; Margeta-Mitrovic, M; Mitrovic, I; Stoffel, M, 2003)
"Neuraxial clonidine is an effective adjunct in the treatment of neuropathic pain and increases acetylcholine concentrations in cerebrospinal fluid in humans."	3.72	Intrathecal clonidine reduces hypersensitivity after nerve injury by a mechanism involving spinal m4 muscarinic receptors. ( Eisenach, JC; Kang, YJ, 2003)
" The purpose of this study was to evaluate stability and compatibility of morphine-clonidine admixtures with an implantable infusion system that is commonly used to treat pain patients."	3.72	Stability and compatibility of morphine-clonidine admixtures in an implantable infusion system. ( Elsberry, DD; Hassenbusch, SJ; Hildebrand, KR, 2003)
" Although adrenergic agonists have potent vascular effects, recent studies suggest that capsaicin-sensitive nociceptors may express adrenoceptors, suggesting that these drugs may directly modulate the function of an important class of pain-signaling neurons in peripheral tissues."	3.72	Adrenergic regulation of capsaicin-sensitive neurons in dental pulp. ( Bowles, WR; Hargreaves, KM; Jackson, DL, 2003)
"Intrathecal clonidine reduces tactile allodynia in animal models of neuropathic pain, and this effect is blocked by atropine."	3.72	Plasticity in action of intrathecal clonidine to mechanical but not thermal nociception after peripheral nerve injury. ( Conklin, D; Eisenach, JC; Paqueron, X, 2003)
"We investigated the interaction between spinally administered bupivacaine and clonidine using an animal model of acute and inflammatory pain."	3.72	Intrathecal clonidine and bupivacaine have synergistic analgesia for acute thermally or inflammatory-induced pain in rats. ( Hanaoka, K; Nishiyama, T, 2004)
" milnacipran, a monoamine reuptake inhibitor, inhibits an acute visceral pain response induced by colorectal or uterine cervical distension."	3.72	The monoamine reuptake inhibitor milnacipran does not affect nociception to acute visceral distension in rats. ( Eisenach, JC; Rao, SG; Shin, SW; Tong, C, 2004)
"Intrathecally administered alpha2-adrenergic receptor subtype-specific antagonists were used to determine which alpha2-adrenergic receptor subtype mediates the analgesic effect of intrathecally administered tizanidine in a chronic constriction injury (CCI) rat model of neuropathic pain."	3.72	Alpha2-adrenergic receptor subtype specificity of intrathecally administered tizanidine used for analgesia for neuropathic pain. ( Dills, CV; Leiphart, JW; Levy, RM, 2004)
"To report a case of possible clonidine-induced hypertension (by Naranjo score) in a patient with a C4 spinal lesion."	3.71	Clonidine-induced hypertension in a patient with a spinal lesion. ( Backo, AL; Clause, SL; Gibbs, KA; Triller, DM, 2002)
"Tizanidine, an alpha2-adrenergic receptor agonist with myospasmolytic action, is indicated for the treatment of back pain either as monotherapy or in combination with nonsteridal anti-inflammatory drugs (NSAIDs)."	3.71	Modulation of NSAID-induced antinociceptive and anti-inflammatory effects by alpha2-adrenoceptor agonists with gastroprotective effects. ( Jain, NK; Kulkarni, SK; Singh, A, 2002)
"Spinally-administered midazolam, a benzodiazepine, and clonidine, an alpha2-adrenergic receptor agonist, have significant synergistic effects on thermally-induced acute and formalin-induced inflammatory pain."	3.71	The synergistic interaction between midazolam and clonidine in spinally-mediated analgesia in two different pain models of rats. ( Hanaoka, K; Nishiyama, T, 2001)
"Intrathecally administered clonidine increases release of spinal acetylcholine, which may be related to its analgesic action in neuropathic pain."	3.70	Intrathecal clonidine alleviates allodynia in neuropathic rats: interaction with spinal muscarinic and nicotinic receptors. ( Chen, SR; Eisenach, JC; Pan, HL, 1999)
"The present data suggest that intrathecal morphine, and to some extent clonidine, but not baclofen, alleviated the abnormal pain-related behaviors in this new rat model of partial peripheral nerve injury."	3.70	Effects of intrathecal morphine, clonidine and baclofen on allodynia after partial sciatic nerve injury in the rat. ( Hao, JX; Wiesenfeld-Hallin, Z; Xu, IS; Xu, XJ, 1999)
"Intrathecal administration of alpha(2) adrenergic agonists, such as clonidine, is capable of alleviating neuropathic pain."	3.70	Role of spinal muscarinic and nicotinic receptors in clonidine-induced nitric oxide release in a rat model of neuropathic pain. ( Chen, SR; Eisenach, J; Pan, HL; Xu, Z, 2000)
"Clonidine increased colonic and rectal compliance, and reduced tone, pain, gas sensation and rectal urgency."	3.70	Towards identifying optimal doses for alpha-2 adrenergic modulation of colonic and rectal motor and sensory function. ( Burton, DD; Camilleri, M; Fett, SL; Kost, L; Malcolm, A; Zinsmeister, AR, 2000)
") morphine, but not the alpha 2-adrenoreceptor agonist clonidine, administered prior to sciatic nerve section, reduced the level of autotomy in rats, which is a behavioural model of neuropathic pain."	3.69	The effects of intrathecal morphine and clonidine on the prevention and reversal of spinal cord hyperexcitability following sciatic nerve section in the rat. ( Luo, L; Puke, CMJ; Wiesenfeld-Hallin, Z, 1994)
" We describe a case of chronic pain following SCI which failed to respond to a variety of approaches including intrathecal administration of morphine."	3.69	Intrathecal morphine and clonidine in the management of spinal cord injury pain: a case report. ( Cousins, MJ; Gray, M; Rutkowski, S; Siddall, PJ, 1994)
"The antinociceptive actions of morphine and tizanidine (an alpha 2-adrenergic agonist) administered intrathecally in a rat model of mononeuropathic pain were investigated."	3.69	A comparison of intrathecally administered narcotic and nonnarcotic analgesics for experimental chronic neuropathic pain. ( Dills, CV; Kim, DL; Leiphart, JW; Levy, RM; Zikel, OM, 1995)
"The aim of the present study was to investigate whether clonidine and morphine interact positively to produce analgesia against the low intensity tonic pain represented by the formalin model in rats."	3.69	Morphine, clonidine coadministration in subanalgesic doses: effective control of tonic pain. ( Gurtu, S; Mukerjee, D; Shukla, S, 1994)
" In addition, we also investigate the action of both HEs against capsaicin-mediated pain."	3.69	Analysis of the mechanisms underlying the antinociceptive effect of the extracts of plants from the genus Phyllanthus. ( Calixto, JB; Filho, VC; Santos, AR; Yunes, RA, 1995)
"To determine the clinical usefulness of the long-term intrathecal administration of midazolam and clonidine in patients with refractory neurogenic and musculoskeletal pain."	3.69	Long-term intrathecal administration of midazolam and clonidine. ( Borg, PA; Krijnen, HJ, 1996)
"To assess the benefit of ketamine addition to a morphine-clonidine-lidocaine mixture administered continuously by the intrathecal route for the treatment of cancer pain."	3.69	[Cancer pain: beneficial effect of ketamine addition to spinal administration of morphine-clonidine-lidocaine mixture]. ( Lemos, D; Muller, A, 1996)
"Direct intraspinal injection of the catecholamines epinephrine and norepinephrine, and the alpha-adrenergic agents dexmedetomidine and clonidine, produced a dose-dependent elevation of pain thresholds in the Northern grass frog, Rana pipiens."	3.69	Spinal administration of adrenergic agents produces analgesia in amphibians. ( Brenner, GM; Stevens, CW, 1996)
"The effects of the intrathecal alpha 2-agonists tizanidine and clonidine and the somatostatin analog octreotide on an experimental rat model of tactile allodynia were investigated to determine the therapeutic potential for treating chronic neuropathic pain."	3.69	Effects of intrathecal nonnarcotic analgesics on chronic tactile allodynia in rats: alpha 2-agonists versus somatostatin analog. ( Kroin, JS; Ono, N; Paice, JA; Penn, RD, 1997)
"The effect of intrathecal morphine (MO) and the alpha 2-adrenoceptor agonists clonidine (CLON) and dexmedetomidine on self-mutilation (autotomy), a behavior that may indicate the presence of neuropathic pain, has been examined in rats."	3.68	The differential effects of morphine and the alpha 2-adrenoceptor agonists clonidine and dexmedetomidine on the prevention and treatment of experimental neuropathic pain. ( Puke, MJ; Wiesenfeld-Hallin, Z, 1993)
"Clonidine was administered in the lumbar epidural space to nine volunteers while monitoring blood pressure, heart rate, finger and toe blood flow, and response to cold pain testing, and while sampling CSF and arterial plasma for clonidine analysis."	3.68	Hemodynamic and analgesic actions of epidurally administered clonidine. ( Detweiler, D; Eisenach, J; Hood, D, 1993)
"Ten patients with deafferentation pain after spinal cord injury were given 150 micrograms clonidine epidurally."	3.68	Cerebrospinal fluid kinetics of epidural clonidine in man. ( Glynn, CJ; Jamous, MA; Teddy, PJ, 1992)
"Epidural clonidine produces analgesia in humans with acute and chronic pain."	3.68	A comparison of two epidural alpha 2-agonists, guanfacine and clonidine, in regard to duration of antinociception, and ventilatory and hemodynamic effects in goats. ( Baudendistel, LJ; Gibbons, JJ; Schweiss, JF; Smith, BD, 1992)
"A patient with disseminated cancer pain failed to obtain pain relief despite the intravenous infusion of hydromorphone at a rate equivalent to over 7 g of morphine/day."	3.67	Failure of epidural opioid to control cancer pain in a patient previously treated with massive doses of intravenous opioid. ( Cousins, MJ; Tanelian, DL, 1989)
"Clonidine was administered by epidural injections with per os relay and long term therapeutic follow-up to 38 patients with deafferentation neurological sequellar pain either fully or partly intractable to classical pain treatments."	3.67	[Thoracolumbar or sacral epidural administration of clonidine in deafferentation pain: possibilities, limits and long-term follow-up]. ( Farcot, JM; Grasser, C; Mercky, F, 1989)
"The jaw-opening reflex (JOR) in anesthetized rats and rabbits was the pain paradigm studied."	3.67	Evidence for alpha adrenoceptor modulation of the nociceptive jaw-opening reflex in rats and rabbits. ( Curtis, AL; Marwah, J, 1986)
"A case is reported in which spinal intrathecal administration of clonidine produced pain."	3.67	Pain after spinal intrathecal clonidine. An adverse interaction with tricyclic antidepressants? ( Hardy, PA; Wells, JC, 1988)
"Epidural clonidine is an alternate way to treat severe pain in man."	3.67	Cerebrospinal fluid and plasma concentrations of clonidine in pigs after epidural, intravenous and intramuscular administration. ( Gordh, T; Hartvig, P, 1986)
"The use of clonidine in the management of opiate abstinence is presented in a patient dependent upon levorphanol tartrate given for chronic pain."	3.66	The use of clonidine for management of opiate abstinence in a chronic pain patient. ( Bakris, GL; Cross, PD; Hammarsten, JE, 1982)
"Sufentanil and clonidine were effective as sedative in patients undergoing heart catheterization."	2.76	Sedation with sufentanil and clonidine in patients undergoing heart catheterization. ( Barros, GA; Castro, PA; Nascimento, Jdos S; Rocha, AP; Santos, KP; Vasconcelos, LM, 2011)
"Gabapentin is an important adjuvant to the management of opiate dependence both in acute detoxification as well as stabilisation phase."	2.71	Gabapentin in the management of pentazocine dependence: a potent analgesic--anticraving agent. ( Jain, MK; Kumar, P, 2003)
"Tizanidine is a centrally acting alpha-2 adrenoreceptor agonist widely used in the treatment of spasticity in patients with cerebral or spinal injury, and it is causing drawsiness in some of them."	2.71	[Effects of tizanidine for refractory sleep disturbance in disabled children with spastic quadriplegia]. ( Cho, K; Fujieda, K; Fukuda, I; Miyamoto, A; Oka, R; Tanaka, H, 2004)
" Effect on pain (including dose-response relationship) was due to 0."	2.70	Effects of an alpha(2)-adrenergic agonist on gastrointestinal transit, colonic motility, and sensation in humans. ( Burton, DD; Camilleri, M; Malcolm, A; McKinzie, S; Szarka, LA; Viramontes, BE; Zinsmeister, AR, 2001)
"Pain was not different in the two groups after tourniquet release."	2.69	Adding clonidine to lidocaine for intravenous regional anesthesia prevents tourniquet pain. ( Bernard, JM; Bonnet, F; Gentili, M, 1999)
"We have studied the use of clonidine combined with low doses of sufentanil and bupivacaine in 45 parturients requiring extradural analgesia for the first stage of labour, in a double-blind, randomized study."	2.68	Extradural clonidine combined with sufentanil and 0.0625% bupivacaine for analgesia in labour. ( Boulétreau, P; Chassard, D; Dailler, F; Golfier, F; Mathon, L; Tournadre, JP, 1996)
"Tizanidine is a well-tolerated and effective drug for symptomatic treatment of spasticity."	2.67	A double-blind, placebo-controlled trial of tizanidine in the treatment of spasticity caused by multiple sclerosis. United Kingdom Tizanidine Trial Group. ( , 1994)
"Mechanistic approaches and multimodal analgesic techniques have been clearly demonstrated to be the most effective pain management strategy to improve outcomes."	2.55	Analgesia in the surgical intensive care unit. ( Brudney, CS; Ehieli, E; Pyati, S; Yalamuri, S, 2017)
"Intubation of the trachea and mechanical ventilation are ubiquitous painful procedures in the neonatal intensive care unit that are poorly assessed and treated."	2.49	Sedation and analgesia to facilitate mechanical ventilation. ( Colby, CE; Nemergut, ME; Yaster, M, 2013)
"Clonidine is an agonist at the alpha2-adrenergic receptor that has been in clinical use for over 40 years."	2.47	Clonidine: clinical pharmacology and therapeutic use in pain management. ( Neil, MJ, 2011)
"Among the more common symptoms is spasticity."	2.41	Management of spasticity, pain, and paroxysmal phenomena in multiple sclerosis. ( Schapiro, RT, 2001)
" It is concluded that co-administration of Vit B12 and morphine could reduce tolerance to analgesic effect of morphine chronic administration and also reduce its withdrawal symptoms."	1.40	Effect of cyanocobalamin (vitamin B12) in the induction and expression of morphine tolerance and dependence in mice. ( Etemad, L; Ghazanfari, S; Hosseinzadeh, H; Imenshahidi, M; Moshiri, M, 2014)
"Uliginosin B is a natural phloroglucinol derivative, obtained from Hypericum species native to South America."	1.40	Determination of pharmacological interactions of uliginosin B, a natural phloroglucinol derivative, with amitriptyline, clonidine and morphine by isobolographic analysis. ( Antonio, CB; da Costa, PF; Müller, LG; Noël, F; Rates, SM; Stolz, ED; von Poser, GL, 2014)
"Whether the additional PTSD and functional neurologic deficits were due to a direct effect of the lightning strike on the central nervous system or a secondary response is open to speculation."	1.39	Central hyperadrenergic state after lightning strike. ( Ahlskog, JE; Craft, JM; Gelfman, R; Kantor, B; Low, PA; Parsaik, AK; Seime, RJ; Sheldon, SH; Singer, W; Staab, JP, 2013)
"Pain was evoked by injection of a formalin solution (5%, 50 μl) into the hindpaw of male Sprague-Dawley rats."	1.37	Antinociceptive effect of intrathecal ginsenosides through alpha-2 adrenoceptors in the formalin test of rats. ( Choi, JI; Huang, LJ; Kim, CM; Kim, WM; Lee, HG; Yoon, MH, 2011)
"Clonidine and ET have been reported to have cardiovascular interactions involving the sympathetic nervous system, but it is not known whether ETA receptor antagonist affects clonidine analgesia."	1.36	Involvement of imidazoline and opioid receptors in the enhancement of clonidine-induced analgesia by sulfisoxazole. ( Andurkar, SV; Boxwalla, M; Gulati, A; Matwyshyn, G; Puppala, BL, 2010)
"Pain was assessed using the formalin test (induced by a subcutaneous injection of 50 microl of a 5% formalin solution to the hindpaw)."	1.35	Evaluation for the interaction between intrathecal melatonin and clonidine or neostigmine on formalin-induced nociception. ( Huang, LJ; Kim, WM; Kim, YO; Lee, HG; Park, HC; Yoon, MH, 2008)
" In the mouse formalin test, DBV injection produced a dramatic leftward shift in the dose-response curve for clonidine-induced analgesia."	1.35	Acupoint stimulation with diluted bee venom (apipuncture) potentiates the analgesic effect of intrathecal clonidine in the rodent formalin test and in a neuropathic pain model. ( Beitz, AJ; Han, HJ; Kim, HW; Kwon, YB; Lee, HJ; Lee, JH; Roh, DH; Seo, HS; Yoon, SY, 2009)
"Neuropathic pain is associated with several sensory abnormalities, including allodynia as well as spontaneous pain."	1.34	Opioid self-administration in the nerve-injured rat: relevance of antiallodynic effects to drug consumption and effects of intrathecal analgesics. ( Buechler, NL; Eisenach, JC; Kim, SA; Martin, TJ; Porreca, F, 2007)
"Morphine tolerance was induced using a 3-day cumulative twice-daily dosing regimen with s."	1.32	Influence of prazosin and clonidine on morphine analgesia, tolerance and withdrawal in mice. ( Lähdesmäki, J; Ozdoğan, UK; Scheinin, M, 2003)
"Treating this pain is often difficult, particularly in elderly patients, owing to iatrogenic effects and to interactions with the pre-existing diseases and treatments frequently present in this age group."	1.32	[Facial anesthetic blocks in the treatment of acute pain during ophthalmic zoster]. ( Chiquet, C; Gain, P; Maugery, J; Michaud, P; Navez, ML; Pascal, J; Thuret, G, 2003)
" In this study, we investigated the dose-response characteristics of IT clonidine, and whether a subeffective dose of clonidine could enhance the effect of SCS in nerve-injured rats with tactile hypersensitivity (allodynia)."	1.32	Intrathecal clonidine potentiates suppression of tactile hypersensitivity by spinal cord stimulation in a model of neuropathy. ( Linderoth, B; Meyerson, BA; Schechtmann, G; Wallin, J, 2004)
"The clonidine response was inhibited by yohimbine (0."	1.32	Clonidine and guanfacine-induced antinociception in visceral pain: possible role of alpha 2/I2 binding sites. ( Hosseini, AR; Khansefid, N; Sabetkasaie, M; Sadat Ladgevardi, MA; Vala, S, 2004)
"CFA injection resulted in significant thermal hyperalgesia throughout the four days of observation."	1.31	Intrathecal clonidine decreases spinal nitric oxide release in a rat model of complete Freund's adjuvant induced inflammatory pain. ( Cheng, JT; Chuang, YC; Lin, CR; Wang, CJ; Yang, LC, 2002)
"Clonidine was also evaluated in combination with ketamine and dextromethorphan."	1.31	Interactions of NMDA antagonists and an alpha 2 agonist with mu, delta and kappa opioids in an acute nociception assay. ( Baker, AK; Hoffmann, VL; Meert, TF, 2002)
"Moxonidine is a mixed I(1) imidazoline/alpha(2)moxonidine=morphine."	1.31	Effects of the I(1) imidazoline/alpha(2)-adrenergic receptor agonist moxonidine in comparison with clonidine in the formalin test in rats. ( Lutz, EA; Shannon, HE, 2000)
"In untreated mice, morphine, fentanyl, clonidine, oxymetazoline, desipramine and lidocaine, but not MK801, produced dose-related antinociception when tested using a 55 degrees C water tail-flick test."	1.31	Pharmacologic reversal of pertussis toxin-induced thermal allodynia in mice. ( Shannon, HE; Womer, DE, 2000)
"3-10 microg) and clonidine (1-30 microg) were administered to obtain the dose-response curves and the 50% effective dose (ED(50)) for each drug."	1.31	Intrathecal carbachol and clonidine produce a synergistic antiallodynic effect in rats with a nerve ligation injury. ( Han, SM; Hwang, JH; Lee, EJ; Park, JY; Park, PH; Sim, JY, 2002)
"Morphine and clonidine were given intrathecally through implanted catheters alone or in a 1:3 fixed ratio."	1.30	Synergistic antinociceptive interactions of morphine and clonidine in rats with nerve-ligation injury. ( Bian, D; Lopez, Y; Nichols, ML; Ossipov, MH; Porreca, F, 1997)
" boluses of ST to generate dose-response curves."	1.30	Spinal infusion of N-methyl-D-aspartate antagonist MK801 induces hypersensitivity to the spinal alpha-2 agonist ST91 in the rat. ( Dunbar, SA; Yaksh, TL, 1997)
"Clonidine was more potent in CCI then in CFA rats in reducing the response to cold."	1.30	The cold plate as a test of nociceptive behaviors: description and application to the study of chronic neuropathic and inflammatory pain models. ( Franssen, M; Goff, JR; Janni, G; Jasmin, L; Kohan, L, 1998)
"Tizanidine (TZD) is an alpha-2-adrenergic drug with potential spinal analgesic action and could be a substitute or additive for intrathecal (i."	1.30	Distribution, tolerability and tissue compatibility of intrathecal tizanidine in the sheep. ( Loew, M; Ochs, G; Tonn, J; Toyka, K, 1998)
" The ability of intrathecally administered clonidine alone or in combination with morphine, DPDPE, or U50,488H to alter thresholds for the production of the visceromotor response was examined."	1.29	Visceral antinociceptive effects of spinal clonidine combined with morphine, [D-Pen2, D-Pen5] enkephalin, or U50,488H. ( Collins, JG; Harada, Y; Kishikawa, K; Kitahata, LM; Nishioka, K, 1995)
"clonidine was neither potentiated by i."	1.29	Neither cholecystokinin nor galanin modulate intrathecal clonidine-induced depression of the nociceptive flexor reflex in the rat. ( Wiesenfeld-Hallin, Z; Xu, XJ, 1993)
"Idazoxan (2."	1.29	Noradrenergic and opioid systems interact to alter the detection of noxious thermal stimuli and facial scratching in monkeys. ( Anton, F; Dubner, R; Kenshalo, DR; Thomas, DA; Williams, GM, 1993)
" Microinjections of medetomidine into the cerebellum or the PAG produced an identical dose-response curve in the tail-flick test as that obtained following microinjection into the RVM."	1.29	The rostroventromedial medulla is not involved in alpha 2-adrenoceptor-mediated antinociception in the rat. ( Hämäläinen, MM; Pertovaara, A, 1993)
"clonidine was reversed by the selective alpha 2-adrenoceptor antagonist atipamezole."	1.29	Effects of intrathecal vs. systemic clonidine in treating chronic allodynia-like response in spinally injured rats. ( Hao, JX; Wiesenfeld-Hallin, Z; Xu, XJ; Yu, W, 1996)
"Clonidine was found to be highly effective in arthritic animals, even at the lower concentration: the elevation in threshold produced by 30 micrograms/kg i."	1.28	Potent antinociceptive effects of clonidine systemically administered in an experimental model of clinical pain, the arthritic rat. ( Besson, JM; Guilbaud, G; Kayser, V, 1992)
"Naloxone pretreatment attenuated this decline."	1.28	Clonidine and yohimbine modulate the effects of naloxone on novelty-induced hypoalgesia. ( Dawes, P; Rochford, J, 1992)
"Evidence suggests that the pain and hyperalgesia in SMP are related to activation of peripheral adrenergic receptors."	1.28	Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain. ( Campbell, JN; Davis, KD; Meyer, RA; Raja, SN; Treede, RD, 1991)
"Neuropeptide Y (NPY) is a 36-amino-acid, C-terminal amidated peptide that is found in bulbospinal pathways and can inhibit the release of the primary afferent C-fiber neurotransmitter, substance P."	1.28	The antinociceptive effects of spinally administered neuropeptide Y in the rat: systematic studies on structure-activity relationship. ( Boublik, JH; Brown, MR; Hua, XY; Rivier, JE; Spicer, MA; Yaksh, TL, 1991)
"Pretreatment with reserpine (2 mg/kg) significantly reduced the antinociceptive activity of FR64822, when tested against acetic acid writhing."	1.28	Involvement of dopamine in the mechanism of action of FR64822, a novel non-opioid antinociceptive compound. ( Nomura, K; Ohkubo, Y; Yamaguchi, I, 1991)
" Dose-response curves for IT morphine were obtained in the presence of fixed doses (0."	1.28	Interaction of intrathecal morphine and ST-91 on antinociception in the rat: dose-response analysis, antagonism and clearance. ( Monasky, MS; Stevens, CW; Yaksh, TL; Zinsmeister, AR, 1990)
" Graded dose-response curves (DRC) were constructed from tail-flick latencies converted to % maximal possible effect (%MPE), and the ED50 calculated."	1.28	Spinal antinociceptive synergy between clonidine and morphine, U69593, and DPDPE: isobolographic analysis. ( Green, J; Harris, S; Lloyd, P; Lozito, R; Messineo, E; Ossipov, MH, 1990)
" dose-response curves for the effect of the chronic drug given as a bolus."	1.28	Potency of infused spinal antinociceptive agents is inversely related to magnitude of tolerance after continuous infusion. ( Stevens, CW; Yaksh, TL, 1989)
"Clonidine therapy was used to alleviate symptoms of narcotic analgesic withdrawal."	1.27	Narcotic bowel syndrome treated with clonidine. Resolution of abdominal pain and intestinal pseudo-obstruction. ( Greenberger, NJ; McPhee, MS; Sandgren, JE, 1984)
"Clonidine pretreatment did not significantly alter the effect of baclofen alone, but reversed the potentiation of the action of baclofen produced by both theophylline and isobutylmethylxanthine."	1.27	Clonidine reverses methylxanthine-induced potentiation of baclofen antinociception. ( Sawynok, J; Steardo, L, 1985)
"Pretreatment with clonidine had only a slight effect on long-term blockade, but yohimbine was without effect."	1.27	Substance P-induced long-term blockade of spinal adrenergic analgesia: reversal by morphine and naloxone. ( Nance, PW; Sawynok, J, 1987)
"Both baclofen and clonidine were injected intraperitoneally in all experiments."	1.27	Role of ascending and descending noradrenergic pathways in the antinociceptive effect of baclofen and clonidine. ( Reid, A; Sawynok, J, 1986)
" Yohimbine, but not naloxone, antagonized the antinociceptive effects of clonidine, whereas both yohimbine and naloxone altered the dose-response function for the effects of clonidine on blood pressure."	1.27	Intrathecal morphine and clonidine: antinociceptive tolerance and cross-tolerance and effects on blood pressure. ( Gebhart, GF; Solomon, RE, 1988)
" After 12 generations of selective breeding, the high antinociceptive response line exhibited about 7 times steeper dose-response curve than did the low antinociceptive response line whereas only small differences were seen with saline alone."	1.27	Selective breeding for levorphanol-induced antinociception on the hot-plate assay: commonalities in mechanism of action with morphine, pentazocine, ethylketocyclazocine, U-50488H and clonidine in mice. ( Belknap, JK; Danielson, PW; Laursen, SE; Noordewier, B, 1987)
" The dose-response curve of depression by morphine alone of C-fiber-evoked activity (ED50 8 micrograms) is significantly shifted by clonidine to the left (ED50 0."	1.27	Mutual potentiation of antinociceptive effects of morphine and clonidine on motor and sensory responses in rat spinal cord. ( Carlsson, KH; Jochim, A; Jurna, I; Wilcox, GL, 1987)
"Naloxone was found to reverse this hypoalgesic state."	1.27	Association between hypoalgesia and hypertension in rats after short-term isolation. ( Fuentes, JA; Naranjo, JR, 1985)

Research

Studies (318)

Authors

Clinical Trials (13)

Trial Overview

Trial Outcomes

Change in Average 10 Meter Time Walking Test (10MTWT) From Baseline to Month 6

Timeframe	Studies, this research(%)	All Research%
pre-1990	69 (21.70)	18.7374
1990's	91 (28.62)	18.2507
2000's	104 (32.70)	29.6817
2010's	42 (13.21)	24.3611
2020's	12 (3.77)	2.80

Authors	Studies
Hlasta, DJ	1
Luttinger, D	1
Perrone, MH	1
Silbernagel, MJ	1
Ward, SJ	1
Haubrich, DR	1
Malhotra, V	1
Vats, M	1
Nath, R	1
Mehta, S	1
Kumar, R	1
Bhalla, M	1
Sinha, JN	1
Shanker, K	1
Pathak, SR	1
Matsushita, Y	1
Manabe, M	1
Kitagawa, I	1
Higuchi, M	1
Hosaka, YZ	1
Kitamura, N	1
Punj, J	1
Garg, H	1
Gomez, G	1
Bagri, NK	1
Thakur, JP	1
Singh, LD	1
Jain, D	1
Darlong, V	1
Pandey, R	1
Karam, C	1
Al Assadi, S	1
Kanazi, G	1
Zeeni, C	1
Huang, H	1
Bai, X	1
Zhang, K	1
Guo, J	1
Wu, S	1
Ouyang, H	1
Sorrieul, J	1
Robert, J	1
Vincent, L	1
Andre, M	1
Bourcier, B	1
Bienfait, F	1
Hamon, SJ	1
Dupoiron, D	1
Devys, C	1
Carlsen Misic, M	1
Eriksson, M	1
Normann, E	1
Pettersson, M	1
Blomqvist, Y	1
Olsson, E	2
Steffen, DA	1
Najafi, A	1
Binkert, CA	1
Bäcke, P	1
Bruschettini, M	1
Sibrecht, G	1
Thernström Blomqvist, Y	1
Dersch-Mills, D	1
Howlett, A	1
Lind, J	1
Marchuk, A	1
Mohammad, K	1
Bromfalk, Å	1
Hultin, M	1
Myrberg, T	1
Engström, Å	1
Walldén, J	1
Donato, J	1
Rao, K	1
Lewis, T	1
Mitchell, A	1
Kelly, J	1
Cook, J	1
Atkinson, N	1
Spain, B	1
Remenyi, B	1
Wade, V	1
Ralph, AP	1
Drummond, PD	2
Morellini, N	1
Finch, PM	1
Birklein, F	1
Knudsen, LF	1
Creamer, M	1
Cloud, G	1
Kossmehl, P	1
Yochelson, M	1
Francisco, GE	1
Ward, AB	1
Wissel, J	1
Zampolini, M	1
Abouihia, A	1
Calabrese, A	1
Saltuari, L	1
Ginosar, Y	1
Riley, ET	1
Angst, MS	1
Parsaik, AK	1
Ahlskog, JE	1
Singer, W	1
Gelfman, R	1
Sheldon, SH	1
Seime, RJ	1
Craft, JM	1
Staab, JP	1
Kantor, B	1
Low, PA	1
Nemergut, ME	1
Yaster, M	1
Colby, CE	1
Delaunois, A	1
De Ron, P	1
Dedoncker, P	1
Rosseels, ML	1
Cornet, M	1
Jnoff, E	1
Hanon, E	1
Guyaux, M	1
Depelchin, BO	1
Fan, QQ	1
Li, L	1
Wang, WT	1
Yang, X	2
Suo, ZW	2
Hu, XD	2
Ghazanfari, S	1
Imenshahidi, M	1
Etemad, L	1
Moshiri, M	1
Hosseinzadeh, H	1
Ohnesorge, H	1
Feng, Z	1
Zitta, K	1
Steinfath, M	1
Albrecht, M	1
Bein, B	1
Wang, XT	1
Lian, X	1
Xu, YM	1
Chapman, CR	1
Bradshaw, DH	1
Donaldson, GW	1
Jacobson, RC	1
Nakamura, Y	1
Milne, B	3
Jhamandas, K	3
Sutak, M	3
Grenier, P	2
Cahill, CM	3
Stone, LS	1
German, JP	1
Kitto, KF	1
Fairbanks, CA	1
Wilcox, GL	2
Makau, CM	2
Towett, PK	2
Abelson, KS	1
Kanui, TI	3
Stolz, ED	1
Müller, LG	1
Antonio, CB	1
da Costa, PF	1
von Poser, GL	1
Noël, F	1
Rates, SM	1
Wu, BT	1
Chen, KT	1
Liu, KS	1
Chen, YW	2
Hung, CH	2
Wang, JJ	2
Bassani, AS	1
Banov, D	1
Ragavendran, JV	1
Laferrière, A	1
Bennett, GJ	1
Ware, MA	1
Gandhi, W	1
Bley, K	1
Schweinhardt, P	1
Coderre, TJ	1
Vo, L	1
Hood, S	1
Nag, S	4
Mokha, SS	4
Ehieli, E	1
Yalamuri, S	1
Brudney, CS	1
Pyati, S	1
Abelson, KSP	1
Malchow, RJ	1
Black, IH	1
Giovannoni, MP	1
Ghelardini, C	1
Vergelli, C	1
Dal Piaz, V	1
Nazarian, A	1
Christianson, CA	1
Hua, XY	2
Yaksh, TL	9
Wang, Q	1
Limbird, LE	1
Ou-Yang, HD	1
Zeng, WA	1
Li, Q	1
He, WX	1
Wang, PZ	1
Lin, LL	1
Zhang, ZQ	1
Liu, XG	1
Nielsen, JB	1
Sjøgren, P	1
Yoon, MH	4
Park, HC	1
Kim, WM	3
Lee, HG	3
Kim, YO	2
Huang, LJ	3
Yoon, SY	2
Roh, DH	2
Kwon, YB	1
Kim, HW	1
Seo, HS	2
Han, HJ	2
Lee, HJ	1
Beitz, AJ	2
Lee, JH	2
Gulati, A	2
Bhalla, S	1
Matwyshyn, G	2
Zhang, Z	1
Andurkar, SV	2
Kim, CM	2
An, TH	1
Feng, X	1
Zhang, F	1
Dong, R	1
Li, W	1
Liu, J	1
Zhao, X	1
Xue, Q	1
Yu, B	1
Xu, J	2
Schreiber, S	2
Frishtick, R	1
Volis, I	1
Rubovitch, V	1
Pick, CG	2
Weizman, R	1
Ulger, F	1
Bozkurt, A	1
Bilge, SS	1
Ilkaya, F	1
Dilek, A	1
Bostanci, MO	1
Ciftcioglu, E	1
Güldogus, F	1
Yao, XH	1
Zhou, P	1
Huang, Y	1
Wang, B	1
Chen, CY	1
Qing, ZH	1
Cardinaletti, C	1
Mattioli, L	1
Ghelfi, F	1
Del Bello, F	1
Giannella, M	1
Bruzzone, A	1
Paris, H	1
Perfumi, M	1
Piergentili, A	1
Quaglia, W	1
Pigini, M	1
Song, S	1
Cao, J	1
Shi, X	1
Miao, X	1
Young, S	3
Vainio, M	1
Scheinin, M	2
Dukat, M	4
Boxwalla, M	1
Puppala, BL	1
Fortinguerra, F	1
Maschi, S	1
Clavenna, A	1
Bonati, M	1
Wallace, MS	1
Rauck, RL	2
Deer, T	1
Attigah, N	1
Kutter, J	1
Demirel, S	1
Hakimi, M	1
Hinz, U	1
Motsch, J	1
Böckler, D	1
Choi, JI	1
Rocha, AP	1
Barros, GA	1
Nascimento, Jdos S	1
Santos, KP	1
Vasconcelos, LM	1
Castro, PA	1
Davoody, L	1
Quiton, RL	1
Lucas, JM	1
Ji, Y	1
Keller, A	1
Masri, R	1
Chu, CC	1
Chen, YC	1
Hsueh, MI	1
Maruta, T	1
Nemoto, T	1
Satoh, S	1
Kanai, T	1
Yanagita, T	1
Wada, A	1
Tsuneyoshi, I	1
Neil, MJ	1
Patel, D	1
Naik, S	1
Misra, A	1
El-Hefnawy, AS	1
Helmy, T	1
El-Assmy, MM	1
Sarhan, O	1
Hafez, AT	1
Dawaba, M	1
Walker, SM	2
Grafe, M	1
Hayashida, K	1
Kimura, M	1
Yoshizumi, M	1
Hobo, S	1
Obata, H	2
Eisenach, JC	17
Dworkin, RH	1
Lin, CR	1
Chuang, YC	1
Cheng, JT	1
Wang, CJ	1
Yang, LC	1
Backo, AL	1
Clause, SL	1
Triller, DM	1
Gibbs, KA	1
Goudas, LC	2
Cousins, MJ	5
Carr, DB	2
Jain, NK	1
Kulkarni, SK	1
Singh, A	1
Lavand'homme, PM	1
Ma, W	1
De Kock, M	2
Baker, AK	1
Hoffmann, VL	1
Meert, TF	1
Blednov, YA	1
Stoffel, M	2
Alva, H	1
Harris, RA	1
Mitrovic, I	1
Margeta-Mitrovic, M	1
Bader, S	1
Jan, LY	1
Basbaum, AI	1
Ozdoğan, UK	1
Lähdesmäki, J	1
Gain, P	1
Thuret, G	1
Chiquet, C	1
Pascal, J	1
Michaud, P	1
Maugery, J	1
Navez, ML	1
Kang, YJ	1
Hildebrand, KR	1
Elsberry, DD	1
Hassenbusch, SJ	1
Hargreaves, KM	1
Jackson, DL	1
Bowles, WR	1
Parisod, E	1
Siddall, PJ	3
Viney, M	1
McClelland, JM	1
Paqueron, X	2
Conklin, D	1
Ackerman, LL	1
Follett, KA	1
Rosenquist, RW	1
De Rossi, R	1
Bucker, GV	1
Varela, JV	1
McCleane, G	1
Kumar, P	1
Jain, MK	1
Bowen, G	1
Viscusi, ER	1
Andonakakis, A	1
Bischoff, P	2
Schmidt, GN	1
Scharein, E	1
Bromm, B	2
Schulte am Esch, J	1
Nishiyama, T	3
Hanaoka, K	4
Hutschala, D	1
Mascher, H	1
Schmetterer, L	1
Klimscha, W	2
Fleck, T	1
Eichler, HG	1
Tschernko, EM	1
Shin, SW	1
Rao, SG	1
Tong, C	1
Maruyama, K	1
Takeda, S	1
Hongo, T	1
Kobayashi, N	1
Kim, C	1
Ogawa, R	3
Zhao, ZQ	2
Lacey, G	1
Hendry, IA	1
Morton, CR	1
Kern, U	1
Martin, C	1
Scheicher, S	1
Müller, H	1
Wesolowska, A	1
Imanaga, K	1
Wajima, Z	2
Inoue, T	2
Schechtmann, G	1
Wallin, J	1
Meyerson, BA	1
Linderoth, B	1
de Padua, AI	1
de Castro, M	1
Schmidt, A	1
Coutinho Neto, J	1
Terra Filho, J	1
Martinez, JA	1
Kayacan, N	1
Arici, G	1
Karsli, B	1
Bigat, Z	1
Akar, M	1
Sabetkasaie, M	1
Vala, S	1
Khansefid, N	1
Hosseini, AR	1
Sadat Ladgevardi, MA	1
Leiphart, JW	2
Dills, CV	2
Levy, RM	2
Koga, K	1
Honda, K	1
Ando, S	1
Harasawa, I	2
Kamiya, HO	1
Takano, Y	1
Tanaka, H	1
Fukuda, I	1
Miyamoto, A	1
Oka, R	1
Cho, K	1
Fujieda, K	1
Rudich, Z	1
Peng, P	1
Dunn, E	1
McCartney, C	1
Classen, AM	1
Wimbish, GH	1
Kupiec, TC	1
Varga, EV	1
Hosohata, K	1
Borys, D	1
Navratilova, E	1
Nylen, A	1
Vanderah, TW	1
Porreca, F	3
Roeske, WR	1
Yamamura, HI	1
Li, X	2
Miura, T	1
Okazaki, R	1
Yoshida, H	1
Namba, H	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Sequential Allocation Study to Determine the ED50 of Dexmetedomidine as an Adjuvant to Lidocaine Intravenous Regional Anesthesia[NCT05342870]		23 participants (Actual)	Interventional	2012-08-31	Completed
Clonidine as Pain Relief During ROP Eye Examinations[NCT04902859]	Phase 4	50 participants (Anticipated)	Interventional	2022-04-25	Recruiting
A Randomized, Controlled, Open-label, Parallel-group, Multi-center Study to Compare the Effect of Intrathecal Baclofen Therapy Versus Best Medical Treatment on Severe Spasticity in Post-stroke Patients After 6 Months Active Treatment[NCT01032239]	Phase 4	61 participants (Actual)	Interventional	2009-11-30	Completed
The Effects of Topical Treatment With Clonidine + Pentoxifylline in Patients With Neuropathic Pain[NCT03342950]	Phase 2	4 participants (Actual)	Interventional	2019-02-19	Terminated (stopped due to Low recruitment due to the COVID-19 pandemic)
Comparison of Ultrasound Guided Femoral Nerve Blockade and Standard Parenteral Opioid Pain Management Alone in Patients With Hip Fracture in the Emergency Department[NCT02381717]		60 participants (Anticipated)	Interventional	2015-08-31	Recruiting
Managing Acute Pain in Critically Ill Non-communicative Palliative Care Patients[NCT02127086]		377 participants (Actual)	Interventional	2015-03-31	Completed
Guanfacine for PONV and Pain After Sinus Surgery[NCT02882854]		84 participants (Actual)	Interventional	2016-11-30	Completed
The Evaluation of the Combination of Magnesium and Lidocaine for the Pretreatment of Pain That is Caused by the Injection of Propofol.[NCT01342510]	Phase 4	200 participants (Actual)	Interventional	2011-04-30	Completed
Hemodynamic Effect of Intrathecal Clonidine in Hypertensive Subjects: A Pilot Study to Assess Its Effectiveness in Hypertensive Subjects With Poor Blood Pressure Control (Phase II)[NCT01297335]	Phase 2	10 participants (Actual)	Interventional	2011-02-28	Completed
Study of the Efficiency of the Ketamine With Low Analgesic Doses, in Association With High Opioids, in the Treatment of the Rebels Pains, in Palliative Phase of the Cancerous Disease[NCT01326325]	Phase 3	24 participants (Actual)	Interventional	2011-07-31	Completed
Transversus Abdominis Plane (TAP) Block for Cesarean Section[NCT01015807]		90 participants (Actual)	Interventional	2009-11-30	Completed
Comparison Between Intravenous and Intrathecal Clonidine in Post-cesarean Analgesia[NCT02550444]		64 participants (Actual)	Interventional	2015-04-30	Completed
Effects of Lidocaine Patch on Intradermal Capsaicin Induced Pain and Hyperalgesia[NCT00373893]	Phase 1	12 participants	Interventional	2005-12-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Change in average 10MTWT from baseline to month 6 beetween ITB and BMT arm. Change=10MTWT at month 6 - 10MTWT at baseline (NCT01032239)
Timeframe: Baseline and month 6

Change in Average Ashworth Scale (AS) in Affected Lower Extremities From Baseline to Month 6

Intervention	seconds (Mean)
ITB Therapy	4.86
Best Medical Treatment (BMT)	-2.48

"AS is a manual test, measuring the resistance to passive movement about a joint with varying degrees of velocity. Scores range from 1-5, with 5 choices. A score of 1 indicates no resistance, and 5 indicates rigidity. The following muscle groups in the lower extremities were assessed: hip flexors, hip adductors, knee extensors, knee flexors, plantar flexors and ankle-dorsal flexors. Average AS was calculated as the average of AS scores of the 6 muscles of the affected lower extremity. Change in average AS in affected lower extremities from baseline to month 6 between ITB and BMT arm was assessed.~Change= AS at month 6 - AS at baseline." (NCT01032239)
Timeframe: Baseline and month 6

Change in Average Ashworth Scale (AS) in Affected Upper Extremities From Baseline to Month 6

Intervention	units on a scale (Mean)
ITB Therapy	-0.99
Best Medical Treatment (BMT)	-0.43

"AS is a manual test, measuring the resistance to passive movement about a joint with varying degrees of velocity. Scores range from 1-5, with 5 choices. A score of 1 indicates no resistance, and 5 indicates rigidity. The following muscle groups in the upper extremities were assessed: wrist flexors, elbow flexors, elbow extensors, shoulder abductors and shoulder adductors. Average AS was calculated as the average of AS scores of the 5 muscles of the affected lower extremities. Change in average AS in affected upper extremities from baseline to month 6 between ITB and BMT arm was assessed.~Change= AS at month 6 - AS at baseline." (NCT01032239)
Timeframe: Baseline and month 6

Change in Functional Independence Measure (FIM) Score From Baseline to Month 6

Intervention	units on a scale (Mean)
ITB Therapy	-0.66
Best Medical Treatment (BMT)	-0.17

FIM contains 18 items composed of 13 motor tasks and 5 cognitive tasks. Tasks are rated on a 7-point ordinal scale that ranges from total assistance (or complete dependence) to complete independence. Ratings should reflect actual observed performance, not capability. Total score ranges from 18 (lowest) to 126 (highest) level of independence. Change in FIM total score from baseline to month 6 between ITB and BMT arm was assessed. Change=FIM score at month 6 - FIM score at baseline. (NCT01032239)
Timeframe: Baseline and month 6

Change in Stroke Specific Quality of Life (SS-QoL ) From Baseline to Month 6

Intervention	units on a scale (Mean)
ITB Therapy	2.68
Best Medical Treatment (BMT)	-2.58

"SS-QoL questionnaire is a self-assessed quality of life questionnaire specifically designed for post-stroke patients. It evaluates 49 items across 12-domains: personality, energy, language, mobility, vision, upper extremity function, thinking, mood, work/productivity, self-care, and family and social roles. Each item is rated on a 5-point Likert Scale, measuring either positive or negative response to a statement. Summary score is composed of an unweighted average of the 12 domain scores, with higher scores indicating better QoL. Total score ranges from 1 to 5. Change in SS-QoL summary score from baseline to month 6 between ITB and BMT arm was assessed.~Change=SS-QoL score at month 6 - SS-QoL score at baseline." (NCT01032239)
Timeframe: Baseline and month 6

Change in Euro QoL Group-5 Dimensional, 3 Level Version (EQ-5D-3L) From Baseline to Month 6

Intervention	units on a scale (Mean)
ITB Therapy	0.26
Best Medical Treatment (BMT)	0.05

"The EQ-5D-3L is a generic measure of health status consisting in the EQ-5D-3L descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system is characterized on five dimensions: mobility, self-care, ability to undertake usual activities, pain and anxiety/depression. Patients were asked to indicate their level of health on each dimension using one of three levels: no health problems, moderate health problems, and severe health problems. Responses from the questionnaire were converted to a single health index utility score; this ranges from -0.595 to 1. EQ VAS records the patient's self-rated health on a vertical visual analogue scale from 0 to 100 where the endpoints are labelled 'Best imaginable health state' (100) and 'Worst imaginable health state' (0). Change in EQ-5D-3L utility score and VAS score from baseline to month 6 between ITB and BMT arm were assessed. Change=EQ-5D-3L utility or VAS score at month 6 - EQ-5D-3L utility or VAS score." (NCT01032239)
Timeframe: Baseline and month 6

Change in Numeric Pain Rating Scale (NPRS) From Baseline to Month 6

Intervention	units on a scale (Mean)
	Utility Score	VAS
Best Medical Treatment (BMT)	0.01	4.40
ITB Therapy	0.09	9.68

"NPRS is designed to assess the level of pain a patient is feeling at a point in time. The following questions has been presented to patients: What is your actual spasticity-related or spasm-related pain? What was your least spasticity-related or spasm-related pain during the last week? What was your worst spasticity-related or spasm-related pain during the last week? The patient indicated how much pain he is feeling on a scale from 0 to 10. A score of 0 (zero) is no pain while a score of 10 (ten) is worst possible pain. Change in NPRS related to actual, least or worst pain from baseline to month 6 between ITB and BMT arm was assessed. Change=NPRS at month 6 - NPRS at baseline." (NCT01032239)
Timeframe: Baseline and month 6

Change in SF-12 (12-item Short Form) From Baseline to Month 6

Intervention	units on a scale (Mean)
	Actual pain	Least Pain	Worst Pain
Best Medical Treatment (BMT)	0.00	0.24	-0.04
ITB Therapy	-1.17	-1.61	-1.35

The SF-12 is generic assessment of health-related quality of life, which evaluates 8 health dimensions (physical functioning, role physical, bodily pain, vitality, social functioning, role emotional, mental health, and general health). Subscale scores for each dimension were aggregated into summary scores for physical (PCS) and mental health (MCS) components (ranging from 0 to 100, with higher scores indicating better health). Changes in the PCS and MCS from baseline to Month 6 were both compared between the BMT and ITB arms. Change=SF-12 score at month 6 - SF-12 score at baseline. (NCT01032239)
Timeframe: Baseline and month 6

Healthcare Resource Utilization

Intervention	units on a scale (Mean)
	PCS	MCS
Best Medical Treatment (BMT)	-1.13	-0.82
ITB Therapy	3.13	1.05

Number of patients with healthcare professional contacts outside of study visits in the ITB and BMT between baseline and months 6 (NCT01032239)
Timeframe: baseline, ITB test (only ITB arm), second assessment (only BMT arm), week 6 (only ITB arm), month 3, month 6

Number of Participants Who Were Able to Transfer From the Wheelchair to Bed Without Human Assistance

Intervention	Participants (Count of Participants)
	Baseline : general practitioner	Baseline : neurologist	Baseline : nurse (hospital setting)	Baseline : nurse (home care)	Baseline : orthopedic surgeon	Baseline : other	ITB test:general practitioner	ITB test: neurologist	ITB test :other	Second Assessment: general practitioner	Second Assessment: neurologist	Second Assessment: nurse (home care)	Second Assessment: other	week 6: general practitioner	week 6: nurse (hospital setting)	week 6: other	month 3: general practitioner	month 3: neurologist	month 3: other	month 6: general practitioner	month 6: neurologist	month 6: other
Best Medical Treatment (BMT)	8	8	0	1	0	13	NA	NA	NA	5	1	1	4	NA	NA	NA	8	3	9	7	2	11
ITB Therapy	14	4	1	0	3	10	1	1	3	NA	NA	NA	NA	4	2	2	7	1	6	8	3	8

Patient was asked to transfer from the wheelchair to bed without human assistance. High level functional patient (HLP) could transfer. Low level functional patient (LLP) was not able to transfer. Comparison of the number and percentage of HLP and LLP between ITB and BMT arms was evaluated. (NCT01032239)
Timeframe: baseline, month 3, month 6

Therapy Satisfaction

Intervention	Participants (Count of Participants)
	Baseline72364475	Baseline72364476	Month 372364475	Month 372364476	Month 672364475	Month 672364476
	HLP	LLP
ITB Therapy	22
Best Medical Treatment (BMT)	24
ITB Therapy	9
Best Medical Treatment (BMT)	21
ITB Therapy	6
ITB Therapy	19
Best Medical Treatment (BMT)	19
ITB Therapy	5
Best Medical Treatment (BMT)	5

"Patients were presented with two statements (I am satisfied with the reduction in spasticity provided by my treatment, and I would recommend this therapy to a friend). They agreed, disagreed or were neutral with the statements." (NCT01032239)
Timeframe: month 6

PACU Length of Stay in Minutes

Intervention	Participants (Count of Participants)
	Patient Satisfaction with Spasticity Reduction72364475	Patient Satisfaction with Spasticity Reduction72364476	Patient Therapy Reccomandation72364475	Patient Therapy Reccomandation72364476
	disagree	neutral	agree
ITB Therapy	2
Best Medical Treatment (BMT)	7
ITB Therapy	4
ITB Therapy	16
Best Medical Treatment (BMT)	11
Best Medical Treatment (BMT)	5
ITB Therapy	3
Best Medical Treatment (BMT)	4
Best Medical Treatment (BMT)	14

(NCT02882854)
Timeframe: Time frame between arrival and discharge in PACU, approximately 90 minutes

Postoperative Nausea Assessment Using 11-point Nausea Scale (nVRS)

Intervention	minutes (Median)
Guanfacine	128
Placebo	110

PONV assessed using nVRS at 24 hours postop when 0 is no nausea and 10 is worst nausea. (NCT02882854)
Timeframe: 24 hours post op

Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS)

Intervention	score on a scale (Median)
Guanfacine	0.00
Placebo	0.00

Postoperative pain assessment using VAS at 24 hours postop when 0 is no pain and 10 is worst pain (NCT02882854)
Timeframe: 24 hours postop

Total Narcotic Requirement in PACU

Intervention	score on a scale (Median)
Guanfacine	3
Placebo	2

Total narcotic requirement in PACU tallied in morphine equivalents during PACU stay (NCT02882854)
Timeframe: Time frame between arrival and discharge in PACU, approximately 90 minutes

Maximum Postoperative Pain Assessment Using 11-point Visual/Verbal Analog (VAS)

Intervention	morphine equivalents (Median)
Guanfacine	8.75
Placebo	7.50

Maximum postoperative pain assessment assessed in PACU at 15, 30 and 60 minutes after PACU arrival using VAS when 0 is no pain and 10 is worst pain (NCT02882854)
Timeframe: 15, 30, 60 minutes after arriving in PACU

Number of Patients With Pain Associated With Injection of Propofol.

Intervention	Participants (Count of Participants)
	15 minutes after PACU admission72482977	15 minutes after PACU admission72482978	30 minutes after PACU admission72482977	30 minutes after PACU admission72482978	60 minutes after PACU admission72482977	60 minutes after PACU admission72482978
	Mild (Pain nVRS 1-5)	Moderate/Severe (Pain nVRS 6-10)	None (Pain nVRS 0)
Guanfacine	31
Placebo	24
Guanfacine	0
Placebo	5
Guanfacine	8
Placebo	10
Guanfacine	18
Placebo	20
Guanfacine	7
Placebo	6
Guanfacine	14
Placebo	14
Guanfacine	12
Placebo	16
Guanfacine	6
Placebo	13
Guanfacine	21
Placebo	12

"Ten seconds following injection of propofol, subjects were asked Are you having pain at your IV site? Any behavioral signs were noted. Injection pain was assessed using the following four point scale: 0 = no pain; 1 = mild pain (pain reported only in response to questioning and without behavioral signs); 2 = moderate pain (pain reported in response to questioning and accompanied by a behavioral sign, or pain reported spontaneously without questioning); and 3 = severe pain (strong vocal response or response accompanied by facial grimacing, arm withdrawal, or tears)." (NCT01342510)
Timeframe: < 1 minute.

Percentage of Participants Reporting Pain With Injection of Propofol

Intervention	participants reporting pain (Number)
Lidocaine	11
Magnesium	25
Lidocaine/Magnesium	15
Control	18

Following injection of the study drug, 50 mg of propofol will be injected. Ten seconds after propofol, subjects will be asked a standard question about pain. Behavioral signs will be noted. Pain will be assessed using a four point scale: 0=no pain, 1=mild pain (pain reported only in response to questioning and without behavioral signs), 2=moderate pain (pain reported in response to questioning and a behavioral sign, or pain reported without questioning), 3=severe pain (strong vocal response or behavioral response). (NCT01342510)
Timeframe: Approximately 10 seconds following administration of propofol.

Change in Blood Pressure After Intrathecal Injection of Clonidine.

Intervention	percentage of patients reporting pain (Number)
Lidocaine	29
Magnesium	57
Lidocaine/Magnesium	41
Control	46

"Subjects baseline blood pressure (systolic blood pressure (SBP), and diastolic blood pressure (DBP)), and blood pressures after clonidine injection was compared against baseline to assess efficacy of clonidine in refractory hypertensive subjects. Subject's blood pressure was monitored continuously after intrathecal injection of clonidine until subjects blood pressure nadir and return to pre clonidine injection level. The mean value reported below are the average changes in blood pressure from baseline (pre clonidine injection) in both SBP and DBP during post clonidine injection blood pressure monitoring for 4 hours.~Blood pressure measurements were collected every 10 minutes for first hour after injection, and every 15 minutes after the first hour, up to 4 hours were averaged to report the change from baseline." (NCT01297335)
Timeframe: Baseline, Every 10 Minutes for first hour after clonidine injection, and every 15 minutes after first hour, until 4 hours after clonidine injection

Changes in Visual Analogue Scale (VAS) Ratings of Sedation and Sensation of Dry Mouth Reported by the Subjects, Pre and 1 Hour Post Injection

Intervention	mm Hg (Mean)
	Change in mean SBP after clonidine injection	Change in DBP after clonidine injection
Intrathecal Clonidine	79	37

Subjects were asked to rate severity of two of the most common side effects of clonidine, sedation and sensation of dry mouth, at pre and post (1 hour after) intrathecal administration of clonidine. The mean changes between pre and post injection VAS ratings of sedation and sensation of dry mouth are reported below. The VAS scale ranges from 1 to 10 cm, with higher values indicating higher level of sedation and higher level of dry mouth. (NCT01297335)
Timeframe: Before clonidine injection (Baseline), and at 1 hour after clonidine injection.

Likert Scale Pain Rating

Intervention	cm (Mean)
	Change in level of sedation	Change in sensation of dry mouth
Intrathecal Clonidine	3.36	3.47

Likert scale is 11 point digital pain rating system that asks subjects to rate their pain from 0 to 10. Rating of 0 means no pain at all, and in increasing order, 10 would mean worst pain imaginable/ unbearable pain. (NCT01297335)
Timeframe: Pre-dose and 1 hour post injection.

Wound Hyperalgesia Index (WHA) Assessed 48 Hrs After Block Placement in the Different Groups

Intervention	units on a scale (Mean)
	Pre-injection average Likert score	Post-injection average Likert score
Intrathecal Clonidine	6.5	3.6

Determine which of three different TAP formulations (Placebo, TAP, Clo-TAP) has the most beneficial effect on the postoperative area of hyperalgesia 48hrs after the start of the cesarean section. The smaller the area of WHA, assessed in cm2, the better the outcome. Area sizes may range from 0 to any size. (NCT01015807)
Timeframe: 48hrs after CS

Intervention	cm^2 (Mean)
Placebo	1.07
TAP (Bupi)	1.27
Clo-TAP (Bupi + Clon)	0.74

Article	Year
Pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia. The Cochrane database of systematic reviews, 2022, 11-10, Volume: 11 Topics: Clonidine; Dexmedetomidine; Humans; Hypothermia, Induced; Infant, Newborn; Morphine Derivatives; Obs	2022
Pharmacology of Common Analgesic and Sedative Drugs Used in the Neonatal Intensive Care Unit. Clinics in perinatology, 2019, Volume: 46, Issue:4 Topics: Acetaminophen; Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Clonidine; C	2019
Sedation and analgesia to facilitate mechanical ventilation. Clinics in perinatology, 2013, Volume: 40, Issue:3 Topics: Analgesics; Analgesics, Opioid; Benzodiazepines; Clonidine; Humans; Hypnotics and Sedatives; Infant;	2013
Analgesia in the surgical intensive care unit. Postgraduate medical journal, 2017, Volume: 93, Issue:1095 Topics: Acetaminophen; Amines; Analgesics; Analgesics, Opioid; Anesthesia, Conduction; Anesthetics, Local; C	2017
The evolution of pain management in the critically ill trauma patient: Emerging concepts from the global war on terrorism. Critical care medicine, 2008, Volume: 36, Issue:7 Suppl Topics: Analgesia; Analgesics; Analgesics, Opioid; Anesthesia, Conduction; Anti-Inflammatory Agents, Non-Ste	2008
The evolution of pain management in the critically ill trauma patient: Emerging concepts from the global war on terrorism. Critical care medicine, 2008, Volume: 36, Issue:7 Suppl Topics: Analgesia; Analgesics; Analgesics, Opioid; Anesthesia, Conduction; Anti-Inflammatory Agents, Non-Ste	2008
The evolution of pain management in the critically ill trauma patient: Emerging concepts from the global war on terrorism. Critical care medicine, 2008, Volume: 36, Issue:7 Suppl Topics: Analgesia; Analgesics; Analgesics, Opioid; Anesthesia, Conduction; Anti-Inflammatory Agents, Non-Ste	2008
The evolution of pain management in the critically ill trauma patient: Emerging concepts from the global war on terrorism. Critical care medicine, 2008, Volume: 36, Issue:7 Suppl Topics: Analgesia; Analgesics; Analgesics, Opioid; Anesthesia, Conduction; Anti-Inflammatory Agents, Non-Ste	2008
Alpha2-agonists as analgesic agents. Medicinal research reviews, 2009, Volume: 29, Issue:2 Topics: Adrenergic alpha-2 Receptor Agonists; Analgesics; Animals; Clonidine; Humans; Pain	2009
[Clonidine in the treatment of cancer pain]. Ugeskrift for laeger, 2008, Nov-03, Volume: 170, Issue:45 Topics: Adrenergic alpha-Agonists; Analgesics; Clonidine; Humans; Injections, Epidural; Injections, Spinal;	2008
Pain management in the paediatric population: the regulatory situation in Europe. Archives of disease in childhood, 2010, Volume: 95, Issue:9 Topics: Adolescent; Analgesics; Buprenorphine; Child; Child, Preschool; Clonidine; Drug and Narcotic Control	2010
Ziconotide combination intrathecal therapy: rationale and evidence. The Clinical journal of pain, 2010, Volume: 26, Issue:7 Topics: Analgesics; Baclofen; Clonidine; Drug Therapy, Combination; Humans; Injections, Spinal; Morphine; om	2010
Clonidine: clinical pharmacology and therapeutic use in pain management. Current clinical pharmacology, 2011, Volume: 6, Issue:4 Topics: Adrenergic alpha-2 Receptor Agonists; Analgesics; Animals; Clonidine; Drug Delivery Systems; Humans;	2011
Combination spinal analgesic chemotherapy: a systematic review. Anesthesia and analgesia, 2002, Volume: 95, Issue:3 Topics: Adrenergic alpha-Agonists; Analgesics, Opioid; Anesthetics, Local; Antineoplastic Agents; Cholineste	2002
Pharmacological management of neuropathic pain. CNS drugs, 2003, Volume: 17, Issue:14 Topics: Analgesics, Opioid; Anesthetics, Local; Anticonvulsants; Antidepressive Agents, Tricyclic; Baclofen;	2003
Spinal agents for acute pain management. Current pain and headache reports, 2004, Volume: 8, Issue:1 Topics: Analgesia, Epidural; Analgesics; Analgesics, Opioid; Anesthetics, Local; Animals; Chronic Disease; C	2004
The use of neuraxial adjuvant drugs (neostigmine, clonidine) in obstetrics. Current opinion in anaesthesiology, 2006, Volume: 19, Issue:3 Topics: Analgesia, Obstetrical; Analgesics; Cesarean Section; Cholinesterase Inhibitors; Clonidine; Female;	2006
MD-354: what is it good for? CNS drug reviews, 2007,Spring, Volume: 13, Issue:1 Topics: Analgesics; Animals; Clonidine; Dose-Response Relationship, Drug; Drug Synergism; Guanidines; Humans	2007
Clonidine: new research in psychotropic drug pharmacology. Medicinal research reviews, 1981,Spring, Volume: 1, Issue:1 Topics: Aggression; Analgesics; Animals; Anxiety Disorders; Arousal; Avoidance Learning; Behavior, Animal; B	1981
Spinal antinociception: clinical aspects. Annals of medicine, 1995, Volume: 27, Issue:2 Topics: Adrenergic alpha-Agonists; Analgesia, Epidural; Analgesics; Clinical Trials as Topic; Clonidine; Dru	1995
Clonidine in pain management. The Annals of pharmacotherapy, 1993, Volume: 27, Issue:3 Topics: Animals; Clinical Trials as Topic; Clonidine; Double-Blind Method; Humans; Injections, Epidural; Inj	1993
Neurophysiology of opioid poorly responsive pain. Cancer surveys, 1994, Volume: 21 Topics: Analgesics, Opioid; Animals; Central Nervous System; Clonidine; Dextromethorphan; Dextrorphan; Dynor	1994
alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology, 1996, Volume: 85, Issue:3 Topics: Adrenergic alpha-Agonists; Analgesia, Epidural; Analgesia, Obstetrical; Anesthesia, Conduction; Clon	1996
alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology, 1996, Volume: 85, Issue:3 Topics: Adrenergic alpha-Agonists; Analgesia, Epidural; Analgesia, Obstetrical; Anesthesia, Conduction; Clon	1996
alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology, 1996, Volume: 85, Issue:3 Topics: Adrenergic alpha-Agonists; Analgesia, Epidural; Analgesia, Obstetrical; Anesthesia, Conduction; Clon	1996
alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology, 1996, Volume: 85, Issue:3 Topics: Adrenergic alpha-Agonists; Analgesia, Epidural; Analgesia, Obstetrical; Anesthesia, Conduction; Clon	1996
alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology, 1996, Volume: 85, Issue:3 Topics: Adrenergic alpha-Agonists; Analgesia, Epidural; Analgesia, Obstetrical; Anesthesia, Conduction; Clon	1996
alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology, 1996, Volume: 85, Issue:3 Topics: Adrenergic alpha-Agonists; Analgesia, Epidural; Analgesia, Obstetrical; Anesthesia, Conduction; Clon	1996
alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology, 1996, Volume: 85, Issue:3 Topics: Adrenergic alpha-Agonists; Analgesia, Epidural; Analgesia, Obstetrical; Anesthesia, Conduction; Clon	1996
alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology, 1996, Volume: 85, Issue:3 Topics: Adrenergic alpha-Agonists; Analgesia, Epidural; Analgesia, Obstetrical; Anesthesia, Conduction; Clon	1996
alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology, 1996, Volume: 85, Issue:3 Topics: Adrenergic alpha-Agonists; Analgesia, Epidural; Analgesia, Obstetrical; Anesthesia, Conduction; Clon	1996
[The use of sirdalud in painful muscle tonic syndromes]. Terapevticheskii arkhiv, 1997, Volume: 69, Issue:10 Topics: Clonidine; Humans; Muscle Relaxants, Central; Muscle Spasticity; Muscle Tonus; Muscular Diseases; Pa	1997
Aquadynia: noradrenergic pain induced by bathing and responsive to clonidine. Journal of the American Academy of Dermatology, 1998, Volume: 38, Issue:2 Pt 2 Topics: Adrenergic alpha-Agonists; Aged; Aged, 80 and over; Baths; Chronic Disease; Clonidine; Female; Human	1998
Alpha 2-agonist agents: a review for CRNAs. CRNA : the clinical forum for nurse anesthetists, 1998, Volume: 9, Issue:3 Topics: Adjuvants, Anesthesia; Adrenergic alpha-Agonists; Clonidine; Humans; Hypertension; Nurse Anesthetist	1998
Promising non-narcotic analgesic techniques for labour. Bailliere's clinical obstetrics and gynaecology, 1998, Volume: 12, Issue:3 Topics: Analgesia, Obstetrical; Analgesics, Non-Narcotic; Clonidine; Epinephrine; Female; Humans; Midazolam;	1998
Management of spasticity, pain, and paroxysmal phenomena in multiple sclerosis. Current neurology and neuroscience reports, 2001, Volume: 1, Issue:3 Topics: Acetates; Amines; Autoimmune Diseases; Baclofen; Benzodiazepines; Botulinum Toxins, Type A; Cannabin	2001
Transdermal clonidine. Neonatal network : NN, 2000, Volume: 19, Issue:2 Topics: Administration, Cutaneous; Analgesics; Clonidine; Dose-Response Relationship, Drug; Drug Tolerance;	2000
Detoxification of nonopiate drugs in the chronic pain setting and clonidine opiate detoxification. The Clinical journal of pain, 1992, Volume: 8, Issue:3 Topics: Analgesics; Chronic Disease; Clonidine; Humans; Pain; Substance Withdrawal Syndrome	1992
The narcotic bowel syndrome. Journal of clinical gastroenterology, 1989, Volume: 11, Issue:2 Topics: Abdomen; Clonidine; Humans; Intestinal Pseudo-Obstruction; Narcotics; Pain; Substance Withdrawal Syn	1989
Migraine. Transactions of the Medical Society of London, 1971, Volume: 87 Topics: Blood Vessels; Cacao; Cheese; Clonidine; Diet Therapy; Eye Diseases; Food; Headache; Hematologic Dis	1971

Article	Year
Clonidine as analgesia during retinopathy of prematurity screening in preterm infants (cloROP): protocol for a randomised controlled trial. BMJ open, 2022, 09-22, Volume: 12, Issue:9 Topics: Analgesia; Analgesics; Clonidine; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premat	2022
Postoperative recovery in preschool-aged children: A secondary analysis of a randomized controlled trial comparing premedication with midazolam, clonidine, and dexmedetomidine. Paediatric anaesthesia, 2023, Volume: 33, Issue:11 Topics: Adrenergic alpha-2 Receptor Agonists; Anesthesia, General; Child; Child, Preschool; Clonidine; Dexme	2023
Effect of Intrathecal Baclofen on Pain and Quality of Life in Poststroke Spasticity. Stroke, 2018, Volume: 49, Issue:9 Topics: Administration, Oral; Aged; Baclofen; Benzodiazepines; Clonidine; Dantrolene; Female; Humans; Infusi	2018
Analgesic and sympatholytic effects of low-dose intrathecal clonidine compared with bupivacaine: a dose-response study in female volunteers. British journal of anaesthesia, 2013, Volume: 111, Issue:2 Topics: Adult; Analgesia; Analgesics; Anesthesia, Spinal; Anesthetics, Local; Bupivacaine; Clonidine; Cross-	2013
Central noradrenergic mechanisms and the acute stress response during painful stimulation. Journal of psychopharmacology (Oxford, England), 2014, Volume: 28, Issue:12 Topics: Adolescent; Adrenergic alpha-2 Receptor Agonists; Adrenergic Neurons; Adult; Brain; Clonidine; Doubl	2014
Effects of topical combinations of clonidine and pentoxifylline on capsaicin-induced allodynia and postcapsaicin tourniquet-induced pain in healthy volunteers: a double-blind, randomized, controlled study. Pain, 2016, Volume: 157, Issue:10 Topics: Adolescent; Adult; Analgesics; Capsaicin; Clonidine; Double-Blind Method; Drug Therapy, Combination;	2016
Involvement of Opioid Receptors and α The journal of pain, 2016, Volume: 17, Issue:11 Topics: Adolescent; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Adult; Bl	2016
Effects of premedication of midazolam or clonidine on perioperative anxiety and pain in children. Bioscience trends, 2009, Volume: 3, Issue:3 Topics: Administration, Oral; Analgesics; Anti-Anxiety Agents; Anxiety; Child; Child, Preschool; Clonidine;	2009
Sedation with sufentanil and clonidine in patients undergoing heart catheterization. Arquivos brasileiros de cardiologia, 2011, Volume: 96, Issue:3 Topics: Adolescent; Adrenergic alpha-2 Receptor Agonists; Adult; Aged; Aged, 80 and over; Analgesics, Opioid	2011
Doxazosin versus tizanidine for treatment of dysfunctional voiding in children: a prospective randomized open-labeled trial. Urology, 2012, Volume: 79, Issue:2 Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-2 Receptor Agonists; Anorexia; Child; Chil	2012
Long-term outcomes during treatment of chronic pain with intrathecal clonidine or clonidine/opioid combinations. Journal of pain and symptom management, 2003, Volume: 26, Issue:1 Topics: Adult; Aged; Aged, 80 and over; Analgesics; Analgesics, Opioid; Chronic Disease; Clonidine; Drug The	2003
Perineal analgesic actions of epidural clonidine in cattle. Veterinary anaesthesia and analgesia, 2003, Volume: 30, Issue:2 Topics: Analgesia, Epidural; Analgesics; Animals; Cattle; Clonidine; Dose-Response Relationship, Drug; Heart	2003
Gabapentin in the management of pentazocine dependence: a potent analgesic--anticraving agent. The Journal of the Association of Physicians of India, 2003, Volume: 51 Topics: Acetates; Amines; Analgesics; Analgesics, Opioid; Anti-Anxiety Agents; Clonidine; Cyclohexanecarboxy	2003
Clonidine induced sedation and analgesia--an EEG study. Journal of neurology, 2004, Volume: 251, Issue:2 Topics: Adult; Analgesics; Central Nervous System; Clonidine; Consciousness; Cross-Over Studies; Dose-Respon	2004
Clonidine added to bupivacaine enhances and prolongs analgesia after brachial plexus block via a local mechanism in healthy volunteers. European journal of anaesthesiology, 2004, Volume: 21, Issue:3 Topics: Adult; Analgesics; Anesthetics, Local; Blood Pressure; Brachial Plexus; Bupivacaine; Clonidine; Cros	2004
Oral clonidine premedication exacerbates hypotension following tourniquet deflation by inhibiting noradrenaline release. Journal of Nippon Medical School = Nippon Ika Daigaku zasshi, 2004, Volume: 71, Issue:1 Topics: Administration, Oral; Adrenergic alpha-Agonists; Adult; Anesthesia, Spinal; Blood Pressure; Clonidin	2004
Effect of oral tizanidine on local-anesthetic infiltration pain during epidural catheterization. Journal of Nippon Medical School = Nippon Ika Daigaku zasshi, 2004, Volume: 71, Issue:2 Topics: Administration, Oral; Adult; Aged; Analgesics; Anesthesia, Epidural; Anesthetics, Local; Catheteriza	2004
Clonidine as a pre-anesthetic agent for flexible bronchoscopy. Respiratory medicine, 2004, Volume: 98, Issue:8 Topics: Adult; Aged; Analgesics; Blood Pressure; Bronchoscopy; Clonidine; Double-Blind Method; Female; Heart	2004
Patient-controlled epidural analgesia in labour: the addition of fentanyl or clonidine to bupivacaine. Agri : Agri (Algoloji) Dernegi'nin Yayin organidir = The journal of the Turkish Society of Algology, 2004, Volume: 16, Issue:3 Topics: Adult; Analgesia, Epidural; Analgesia, Patient-Controlled; Analgesics; Blood Pressure; Bupivacaine;	2004
[Effects of tizanidine for refractory sleep disturbance in disabled children with spastic quadriplegia]. No to hattatsu = Brain and development, 2004, Volume: 36, Issue:6 Topics: Adolescent; Adrenergic alpha-Agonists; Adult; Child; Child, Preschool; Clonidine; Disabled Children;	2004
Stability of clonidine in clonidine-hydromorphone mixture from implanted intrathecal infusion pumps in chronic pain patients. Journal of pain and symptom management, 2004, Volume: 28, Issue:6 Topics: Analgesics; Chronic Disease; Clonidine; Complex Mixtures; Drug Combinations; Drug Stability; Drug St	2004
Clonidine effects on pain evoked SII activity in humans. European journal of pain (London, England), 2006, Volume: 10, Issue:8 Topics: Adrenergic alpha-Agonists; Adult; Clonidine; Dose-Response Relationship, Drug; Double-Blind Method;	2006
Clonidine-ephedrine combination reduces pain on injection of propofol and blunts hemodynamic stress responses during the induction sequence. Journal of clinical anesthesia, 2006, Volume: 18, Issue:3 Topics: Analgesics; Anesthetics, Intravenous; Clonidine; Ephedrine; Female; Hemodynamics; Humans; Male; Midd	2006
Does clonidine 50 microg improve cervical plexus block obtained with ropivacaine 150 mg for carotid endarterectomy? A randomized, double-blinded study. Journal of clinical anesthesia, 2006, Volume: 18, Issue:8 Topics: Aged; Aged, 80 and over; Amides; Analgesics; Anesthetics, Local; Cervical Plexus; Clonidine; Double-	2006
Effect of clonidine on ICP and on the hemodynamic responses to nociceptive stimuli in patients with brain tumors. Journal of neurosurgical anesthesiology, 1995, Volume: 7, Issue:3 Topics: Adrenergic alpha-Agonists; Adult; Aged; Anesthesia; Brain Neoplasms; Clonidine; Female; Hemodynamics	1995
Transdermal clonidine compared to placebo in painful diabetic neuropathy using a two-stage 'enriched enrollment' design. Pain, 1995, Volume: 60, Issue:3 Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Clonidine; Cross-Over Studies; Diabetic N	1995
A double-blind, placebo-controlled trial of tizanidine in the treatment of spasticity caused by multiple sclerosis. United Kingdom Tizanidine Trial Group. Neurology, 1994, Volume: 44, Issue:11 Suppl 9 Topics: Activities of Daily Living; Adolescent; Adult; Aged; Clonidine; Double-Blind Method; Female; Humans;	1994
Epidural clonidine treatment for refractory reflex sympathetic dystrophy. Anesthesiology, 1993, Volume: 79, Issue:6 Topics: Adult; Analgesics; Blood Pressure; Chronic Disease; Clonidine; Heart Rate; Humans; Injections, Epidu	1993
The effects of imipramine, amitriptyline and clonidine administered by iontophoresis on the pain threshold. Acta anaesthesiologica Belgica, 1995, Volume: 46, Issue:3-4 Topics: Adrenergic alpha-Agonists; Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Clonidine; Humans	1995
A double-blind randomised comparison of the effects of epidural clonidine, lignocaine and the combination of clonidine and lignocaine in patients with chronic pain. Pain, 1996, Volume: 64, Issue:2 Topics: Adrenergic alpha-Agonists; Adult; Aged; Analgesia, Epidural; Anesthetics, Local; Chronic Disease; Cl	1996
Extradural clonidine combined with sufentanil and 0.0625% bupivacaine for analgesia in labour. British journal of anaesthesia, 1996, Volume: 77, Issue:4 Topics: Adrenergic alpha-Agonists; Analgesia, Epidural; Analgesia, Obstetrical; Analgesics, Opioid; Anesthet	1996
[Influence of preanesthetic medication on the effect of a local anesthetic tape]. Masui. The Japanese journal of anesthesiology, 1997, Volume: 46, Issue:9 Topics: Adjuvants, Anesthesia; Administration, Topical; Adult; Aged; Anesthetics, Local; Anti-Anxiety Agents	1997
Epidural epinephrine and clonidine: segmental analgesia and effects on different pain modalities. Anesthesiology, 1997, Volume: 87, Issue:4 Topics: Adrenergic alpha-Agonists; Adult; Analgesia, Epidural; Clonidine; Cross-Over Studies; Double-Blind M	1997
Intravenous regional clonidine in the management of sympathetically maintained pain. Anesthesiology, 1998, Volume: 89, Issue:2 Topics: Adult; Clonidine; Female; Humans; Injections, Intravenous; Male; Middle Aged; Pain; Pain Measurement	1998
Intrathecal, but not intravenous, clonidine reduces experimental thermal or capsaicin-induced pain and hyperalgesia in normal volunteers. Anesthesia and analgesia, 1998, Volume: 87, Issue:3 Topics: Adrenergic alpha-Agonists; Adult; Analgesics; Blood Pressure; Capsaicin; Clonidine; Double-Blind Met	1998
Intrathecal, but not intravenous, clonidine reduces experimental thermal or capsaicin-induced pain and hyperalgesia in normal volunteers. Anesthesia and analgesia, 1998, Volume: 87, Issue:3 Topics: Adrenergic alpha-Agonists; Adult; Analgesics; Blood Pressure; Capsaicin; Clonidine; Double-Blind Met	1998
Intrathecal, but not intravenous, clonidine reduces experimental thermal or capsaicin-induced pain and hyperalgesia in normal volunteers. Anesthesia and analgesia, 1998, Volume: 87, Issue:3 Topics: Adrenergic alpha-Agonists; Adult; Analgesics; Blood Pressure; Capsaicin; Clonidine; Double-Blind Met	1998
Intrathecal, but not intravenous, clonidine reduces experimental thermal or capsaicin-induced pain and hyperalgesia in normal volunteers. Anesthesia and analgesia, 1998, Volume: 87, Issue:3 Topics: Adrenergic alpha-Agonists; Adult; Analgesics; Blood Pressure; Capsaicin; Clonidine; Double-Blind Met	1998
[Controlled analgesia in a burn patient: fentanyl sparing effect of clonidine]. Annales francaises d'anesthesie et de reanimation, 1998, Volume: 17, Issue:1 Topics: Adolescent; Adrenergic alpha-Agonists; Adult; Analgesia, Patient-Controlled; Burns; Clonidine; Doubl	1998
Adding clonidine to lidocaine for intravenous regional anesthesia prevents tourniquet pain. Anesthesia and analgesia, 1999, Volume: 88, Issue:6 Topics: Adrenergic alpha-Agonists; Adult; Anesthesia, Conduction; Anesthesia, Intravenous; Anesthetics, Loca	1999
Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-induced allodynia. Pain, 2000, Volume: 84, Issue:1 Topics: Adult; Analgesics; Blood Pressure; Capsaicin; Clonidine; Dose-Response Relationship, Drug; Female; H	2000
The efficacy of intrathecal morphine and clonidine in the treatment of pain after spinal cord injury. Anesthesia and analgesia, 2000, Volume: 91, Issue:6 Topics: Adult; Aged; Analgesics, Opioid; Blood Pressure; Clonidine; Double-Blind Method; Female; Heart Rate;	2000
Open-label dose-titration safety and efficacy study of tizanidine hydrochloride in the treatment of spasticity associated with chronic stroke. Stroke, 2001, Volume: 32, Issue:8 Topics: Clonidine; Dose-Response Relationship, Drug; Female; Hand Strength; Humans; Male; Middle Aged; Muscl	2001
Orally administered clonidine significantly reduces pain during injection of propofol. British journal of anaesthesia, 2001, Volume: 86, Issue:6 Topics: Administration, Oral; Adrenergic alpha-Agonists; Adult; Chi-Square Distribution; Clonidine; Female;	2001
Effects of an alpha(2)-adrenergic agonist on gastrointestinal transit, colonic motility, and sensation in humans. American journal of physiology. Gastrointestinal and liver physiology, 2001, Volume: 281, Issue:6 Topics: Adrenergic alpha-Agonists; Adult; Biomechanical Phenomena; Clonidine; Colon; Compliance; Dose-Respon	2001
Continuous intrathecal clonidine administration for the treatment of neuropathic pain. Stereotactic and functional neurosurgery, 2000, Volume: 75, Issue:4 Topics: Adrenergic alpha-Agonists; Adult; Aged; Analgesics; Analgesics, Opioid; Buprenorphine; Chronic Disea	2000
Clonidine in acute and chronic pain. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 1992, Apr-18, Volume: 81, Issue:8 Topics: Acute Disease; Chronic Disease; Clonidine; Female; Humans; Pain	1992
Transdermal clonidine versus placebo in painful diabetic neuropathy. Pain, 1992, Volume: 48, Issue:3 Topics: Administration, Cutaneous; Adult; Aged; Clonidine; Diabetic Neuropathies; Double-Blind Method; Femal	1992
[Analgesic effects of an oral dose of clonidine]. Schweizerische medizinische Wochenschrift, 1989, Dec-02, Volume: 119, Issue:48 Topics: Administration, Oral; Adult; Analgesics; Blood Pressure; Clonidine; Humans; Male; Pain; Pain Measure	1989
Prevention of tourniquet pain by spinal isobaric bupivacaine with clonidine. British journal of anaesthesia, 1989, Volume: 63, Issue:1 Topics: Adult; Aged; Anesthesia, Spinal; Bupivacaine; Clonidine; Drug Evaluation; Female; Humans; Male; Pain	1989
Role of spinal noradrenergic system in transmission of pain in patients with spinal cord injury. Lancet (London, England), 1986, Nov-29, Volume: 2, Issue:8518 Topics: Adult; Aged; Central Nervous System; Clonidine; Female; Humans; Injections, Epidural; Male; Middle A	1986
A double-blind comparison between epidural morphine and epidural clonidine in patients with chronic non-cancer pain. Pain, 1988, Volume: 34, Issue:2 Topics: Adult; Aged; Chronic Disease; Clonidine; Double-Blind Method; Female; Humans; Injections, Spinal; Ma	1988

clonidine and Ache