fentanyl and Allodynia studies

Fentanyl: A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)
fentanyl : A monocarboxylic acid amide resulting from the formal condensation of the aryl amino group of N-phenyl-1-(2-phenylethyl)piperidin-4-amine with propanoic acid.

Research Excerpts

Excerpt	Relevance	Reference
"Our results showed that patients undergoing coronary artery bypass surgery receiving fentanyl anesthesia developed postoperative tactile allodynia and thermal hyperalgesia and this was more prominent in high dose group."	9.19	Acute high dose-fentanyl exposure produces hyperalgesia and tactile allodynia after coronary artery bypass surgery. ( Cinar, S; Doganci, S; Dogrul, A; Eksert, S; Eskin, MB; Ince, ME; Ozkan, G; Yildirim, V, 2014)
"The opioids buprenorphine and fentanyl significantly potentiate the effect of descending pain inhibition in healthy volunteers."	9.16	A double-blind, placebo-controlled study on the effect of buprenorphine and fentanyl on descending pain modulation: a human experimental study. ( Andresen, T; Arendt-Nielsen, L; Drewes, AM; Malver, LP; Mansikka, H; Oksche, A, 2012)
"3°C cold water), nerve growth factor-induced muscle soreness and intradermal capsaicin-induced hyperalgesia and allodynia."	9.15	Pharmacokinetic/pharmacodynamic relationships of transdermal buprenorphine and fentanyl in experimental human pain models. ( Andresen, T; Arendt-Nielsen, L; Christrup, LL; Drewes, AM; Foster, DJ; Upton, RN, 2011)
"To determine the effects of systemic fentanyl analgesia in preventing the pain related to the administration of retrobulbar anesthesia and cataract surgery."	9.10	Effects of fentanyl on pain and hemodynamic response after retrobulbar block in patients having phacoemulsification. ( Ermis, SS; Inan, UU; Oztürk, F; Sivaci, RG, 2003)
"Fentanyl is an opioid commonly prescribed for cancer pain."	7.88	Analgesic effects of systemic fentanyl on cancer pain are mediated by not only central but also peripheral opioid receptors in mice. ( Andoh, T; Kuraishi, Y; Saiki, I; Shinohara, A, 2018)
" Here, by using a chronic inflammation model, namely subplantar injection of Complete Freund's adjuvant, we show a peripheral synergistic interaction between the histamine H(3) receptor agonist R-(alpha)-methylhistamine and fentanyl on the inhibition of thermal hyperalgesia and of peripheral substance P accumulation."	7.76	Histamine H3 receptor activation potentiates peripheral opioid-mediated antinociception: substance P role in peripheral inflammation in mice. ( Ciruela, F; Fernández-Dueñas, V; Gandía, J; Planas, E; Poveda, R; Sánchez, S, 2010)
"Given preemptively, nefopam may be effective at improving postoperative pain management and at reducing the risk of developing postoperative chronic pain, because the drug has both analgesic and antihyperalgesic properties."	7.75	Long-term pain vulnerability after surgery in rats: prevention by nefopam, an analgesic with antihyperalgesic properties. ( Chateauraynaud, J; Laboureyras, E; Richebé, P; Simonnet, G, 2009)
"A 62-year-old man receiving subcutaneous fentanyl for the management of cancer pain developed generalized central excitation after an overdose of 5000 micrograms of fentanyl."	7.69	Acute neuropsychiatric findings in a patient receiving fentanyl for cancer pain. ( Bruera, E; Pereira, J, 1997)
"Opioid-induced hyperalgesia is a phenomenon defined by increasing pain after opioid exposure with the worsening of pain occurring when opioid doses are increased."	6.52	Fentanyl-induced hyperalgesia in acute pain management. ( Kane-Gill, SL; Lyons, PJ; Nery, JP; Rivosecchi, RM, 2015)
"Moreover, fentany-linduced-hyperalgesia and changes in the expression of the aforementioned proteins can be attenuated by TAK-242, an inhibitor of TLR4, as well as ketamine."	5.91	A single dose of ketamine relieves fentanyl-induced-hyperalgesia by reducing inflammation initiated by the TLR4/NF-κB pathway in rat spinal cord neurons. ( Chang, L; Chen, J; Li, Q; Liu, P; Luo, Q; Shu, H; Wang, L; Wu, G; Xiong, Y; Zhou, X, 2023)
"Withdrawal symptoms are severely unpleasant, prolonged, and frequently hinder recovery or lead to relapse."	5.62	Divergent profiles of fentanyl withdrawal and associated pain in mice and rats. ( Arakawa, K; Cramer, N; Fox, ME; Jenne, C; Keller, A; Uddin, O, 2021)
"Remifentanil infusion has been strongly linked to both tolerance and OIH in these patients; however, the impact of using an intraoperative fentanyl infusion has not been well studied."	5.51	Fentanyl versus remifentanil-based TIVA for pediatric scoliosis repair: does it matter? ( Ahn, S; Gecelter, R; Kars, MS; Merwin, S; Poon, S; Rothman, A; Villacres Mori, B; Wendolowski, S, 2019)
"In contrast to the opioid, chronic hyperalgesia did not interfere with the reinforcing effect of food."	5.39	Effect of chronic pain on fentanyl self-administration in mice. ( Fairbanks, CA; Kitto, KF; Krumenacher, P; Peterson, CD; Wade, CL; Wilcox, GL, 2013)
"Pain was well controlled."	5.35	Fentanyl-induced neurotoxicity and paradoxic pain. ( George, ML; Okon, TR, 2008)
"Fifty percent N2O strongly reduced hyperalgesia induced by a first inflammation and its enhancement by fentanyl, and prevented exaggerated hyperalgesia induced by second inflammatory pain or NNES."	5.34	Nitrous oxide (N2O) prevents latent pain sensitization and long-term anxiety-like behavior in pain and opioid-experienced rats. ( Bessière, B; Contarino, A; Laboureyras, E; Laulin, JP; Richebé, P; Simonnet, G, 2007)
"A higher dose of fentanyl led to significantly decreased pain scores as measured by the numeric rating scale (0."	5.22	Does Fentanyl Lead to Opioid-induced Hyperalgesia in Healthy Volunteers?: A Double-blind, Randomized, Crossover Trial. ( Bandschapp, O; Dolder, P; Filitz, J; Mauermann, E; Rentsch, KM; Ruppen, W, 2016)
"Our results showed that patients undergoing coronary artery bypass surgery receiving fentanyl anesthesia developed postoperative tactile allodynia and thermal hyperalgesia and this was more prominent in high dose group."	5.19	Acute high dose-fentanyl exposure produces hyperalgesia and tactile allodynia after coronary artery bypass surgery. ( Cinar, S; Doganci, S; Dogrul, A; Eksert, S; Eskin, MB; Ince, ME; Ozkan, G; Yildirim, V, 2014)
"The opioids buprenorphine and fentanyl significantly potentiate the effect of descending pain inhibition in healthy volunteers."	5.16	A double-blind, placebo-controlled study on the effect of buprenorphine and fentanyl on descending pain modulation: a human experimental study. ( Andresen, T; Arendt-Nielsen, L; Drewes, AM; Malver, LP; Mansikka, H; Oksche, A, 2012)
"Buprenorphine, but not fentanyl, showed analgesic effects against experimentally induced, bone-associated pain and primary hyperalgesia compared with placebo."	5.15	Effect of transdermal opioids in experimentally induced superficial, deep and hyperalgesic pain. ( Andresen, T; Arendt-Nielsen, L; Drewes, AM; Mansikka, H; Oksche, A; Staahl, C, 2011)
"3°C cold water), nerve growth factor-induced muscle soreness and intradermal capsaicin-induced hyperalgesia and allodynia."	5.15	Pharmacokinetic/pharmacodynamic relationships of transdermal buprenorphine and fentanyl in experimental human pain models. ( Andresen, T; Arendt-Nielsen, L; Christrup, LL; Drewes, AM; Foster, DJ; Upton, RN, 2011)
"To determine the effects of systemic fentanyl analgesia in preventing the pain related to the administration of retrobulbar anesthesia and cataract surgery."	5.10	Effects of fentanyl on pain and hemodynamic response after retrobulbar block in patients having phacoemulsification. ( Ermis, SS; Inan, UU; Oztürk, F; Sivaci, RG, 2003)
" His pain and agitation were difficult to manage but improved after he received ketamine."	4.12	Suspected opioid-induced hyperalgesia in an infant following surgery: A case report. ( Efune, PN; Rebstock, SE, 2022)
"Opioids like fentanyl remain the mainstay treatment for chronic pain."	4.12	Sex-specific role of the circadian transcription factor NPAS2 in opioid tolerance, withdrawal and analgesia. ( Barko, K; Logan, RW; Puig, S; Seney, ML; Shelton, MA, 2022)
"We report the case of a 60 year old patient on chronic Intrathecal combined fentanyl and Bupivacaine who had worsening pain with increasing doses and improved after weaning off intrathecal opioids."	3.91	Opioid Induced Hyperalgesia with Intrathecal Infusion of High-Dose Fentanyl. ( Acquadro, MA; Cheng, Y; Farah, F; Gerges, FJ; Kalaydjian, A, 2019)
"Fentanyl is an opioid commonly prescribed for cancer pain."	3.88	Analgesic effects of systemic fentanyl on cancer pain are mediated by not only central but also peripheral opioid receptors in mice. ( Andoh, T; Kuraishi, Y; Saiki, I; Shinohara, A, 2018)
"Antinociceptive effect of narcotic analgesics, fentanyl, oxycodone and methadone in inflammatory pain state was described in the von Frey filament test using the complete Freund's adjuvant (CFA)-induced mouse inflammatory pain model."	3.80	Differential alternation of the antinociceptive effect of narcotic analgesics on the inflammatory pain state. ( Aoki, Y; Mizoguchi, H; Sakurada, S; Sakurada, T; Watanabe, C, 2014)
"The study showed that gabapentin can significantly prevented opioid-induced hyperalgesia (OIH) induced caused by fentanyl and morphine, suggesting a role for the addition of gabapentin in the perioperative period and during chronic pain treatment as an effective drug to prevent OIH."	3.78	Role of gabapentin in preventing fentanyl- and morphine-withdrawal-induced hyperalgesia in rats. ( Wei, W; Wei, X, 2012)
" Here, by using a chronic inflammation model, namely subplantar injection of Complete Freund's adjuvant, we show a peripheral synergistic interaction between the histamine H(3) receptor agonist R-(alpha)-methylhistamine and fentanyl on the inhibition of thermal hyperalgesia and of peripheral substance P accumulation."	3.76	Histamine H3 receptor activation potentiates peripheral opioid-mediated antinociception: substance P role in peripheral inflammation in mice. ( Ciruela, F; Fernández-Dueñas, V; Gandía, J; Planas, E; Poveda, R; Sánchez, S, 2010)
"Given preemptively, nefopam may be effective at improving postoperative pain management and at reducing the risk of developing postoperative chronic pain, because the drug has both analgesic and antihyperalgesic properties."	3.75	Long-term pain vulnerability after surgery in rats: prevention by nefopam, an analgesic with antihyperalgesic properties. ( Chateauraynaud, J; Laboureyras, E; Richebé, P; Simonnet, G, 2009)
" After the treatment of mice for 6 days with implanted morphine pellets followed by their removal, both thermal hyperalgesia and mechanical allodynia were documented."	3.71	A murine model of opioid-induced hyperalgesia. ( Angst, MS; Clark, JD; Li, X, 2001)
"In this experimental pain model, activation of peripheral mu or kappa opioid receptors can attenuate capsaicin-induced thermal hyperalgesia in rats."	3.70	Local administration of mu or kappa opioid agonists attenuates capsaicin-induced thermal hyperalgesia via peripheral opioid receptors in rats. ( Johnson, MD; Ko, MC; Tuchman, JE; Wiesenauer, K; Woods, JH, 2000)
"A 62-year-old man receiving subcutaneous fentanyl for the management of cancer pain developed generalized central excitation after an overdose of 5000 micrograms of fentanyl."	3.69	Acute neuropsychiatric findings in a patient receiving fentanyl for cancer pain. ( Bruera, E; Pereira, J, 1997)
"The dosage of fentanyl-nefopam IV-PCA was significantly less in C group than R group for postoperative 24 h."	3.11	Effect of remifentanil on post-operative analgesic consumption in patients undergoing shoulder arthroplasty after interscalene brachial plexus block: a randomized controlled trial. ( Bae, H; Kim, JT; Kim, Y; Lim, YJ; Park, SK; Sakura, S; Yoo, S, 2022)
"Following extubation, withdrawal symptoms were assessed by a modification of the Finnegan score."	2.78	Remifentanil-induced tolerance, withdrawal or hyperalgesia in infants: a randomized controlled trial. RAPIP trial: remifentanil-based analgesia and sedation of paediatric intensive care patients. ( Harnischmacher, U; Junghaenel, S; Link, F; Oberthuer, A; Roth, B; Stuetzer, H; Welzing, L, 2013)
"The intensity of postoperative pain was similar in both groups (VAS, <3) CONCLUSIONS: Remifentanil showed good analgesic properties during laparoscopic gastric banding surgery."	2.77	Comparison of different anesthetic regimens in patients undergoing laparoscopic adjustable gastric banding operations: a prospective randomized trial. ( Aksionova, D; Brimas, G; Cincilevičiūtė, G; Kontrimavičiūtė, E; Sipylaitė, J, 2012)
"Pre-treatment with fentanyl 1."	2.73	Administration of fentanyl before remifentanil-based anaesthesia has no influence on post-operative pain or analgesic consumption. ( Hoymork, SC; Lenz, H; Raeder, J, 2008)
"Ketamine failed to inhibit both secondary hyperalgesia and axon reflex flare as long as nonlocal anesthetic concentrations were applied."	2.69	The effects of intradermal fentanyl and ketamine on capsaicin-induced secondary hyperalgesia and flare reaction. ( Blunk, JA; Koppert, W; Likar, R; Schmelz, M; Sittl, R; Zeck, S, 1999)
"These results suggest that hyperalgesia induced by a tourniquet may be a useful technique for the investigation of the anti-nociceptive effects of analgesic drugs in sheep."	2.67	Effects of non-steroidal anti-inflammatory drugs on the hyperalgesia to noxious mechanical stimulation induced by the application of a tourniquet to a forelimb of sheep. ( Nolan, AM; Welsh, EM, 1994)
"The surgical wound hyperalgesia was assessed by measuring pain threshold to pressure on the wound by using an algometer, and also by measuring the intensity of pain to suprathreshold pressure on the wound with the visual analog self-rating method."	2.67	Preemptive effect of fentanyl and ketamine on postoperative pain and wound hyperalgesia. ( Bradley, EL; Finger, J; Isakson, A; Kissin, I; Oz, Y; Tverskoy, M, 1994)
"Opioid-induced hyperalgesia is a phenomenon defined by increasing pain after opioid exposure with the worsening of pain occurring when opioid doses are increased."	2.52	Fentanyl-induced hyperalgesia in acute pain management. ( Kane-Gill, SL; Lyons, PJ; Nery, JP; Rivosecchi, RM, 2015)
"Inhibition of these neurons alleviates hyperalgesia in male OIH rats but exerts an opposite effect in male control rats."	1.91	HCN-Channel-Dependent Hyperexcitability of the Layer V Pyramidal Neurons in IL-mPFC Contributes to Fentanyl-Induced Hyperalgesia in Male Rats. ( Gan, S; Li, CH; Luo, F; Wang, X; Zhang, Z; Zhu, P, 2023)
"Moreover, fentany-linduced-hyperalgesia and changes in the expression of the aforementioned proteins can be attenuated by TAK-242, an inhibitor of TLR4, as well as ketamine."	1.91	A single dose of ketamine relieves fentanyl-induced-hyperalgesia by reducing inflammation initiated by the TLR4/NF-κB pathway in rat spinal cord neurons. ( Chang, L; Chen, J; Li, Q; Liu, P; Luo, Q; Shu, H; Wang, L; Wu, G; Xiong, Y; Zhou, X, 2023)
"Opioid-induced hyperalgesia (OIH) is a problem associated with prolonged use of opioids in chronic pain management, and its effective treatment has been hampered by lack of mechanistic evidence."	1.72	Inhibition of Oligodendrocyte Apoptosis in the Prelimbic Medial Prefrontal Cortex Prevents Fentanyl-induced Hyperalgesia in Rats. ( Cui, LL; Gan, SF; Li, CH; Luo, F; Wang, XX; Xiao, J; Zhang, ZR, 2022)
"Withdrawal symptoms are severely unpleasant, prolonged, and frequently hinder recovery or lead to relapse."	1.62	Divergent profiles of fentanyl withdrawal and associated pain in mice and rats. ( Arakawa, K; Cramer, N; Fox, ME; Jenne, C; Keller, A; Uddin, O, 2021)
"Remifentanil infusion has been strongly linked to both tolerance and OIH in these patients; however, the impact of using an intraoperative fentanyl infusion has not been well studied."	1.51	Fentanyl versus remifentanil-based TIVA for pediatric scoliosis repair: does it matter? ( Ahn, S; Gecelter, R; Kars, MS; Merwin, S; Poon, S; Rothman, A; Villacres Mori, B; Wendolowski, S, 2019)
"The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG for more than 7 days and increase of ionized calcium-binding adapter molecule 1 in the spinal cord."	1.48	Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats. ( Chang, L; Luo, Q; Shu, H; Tao, Y; Ye, F, 2018)
"Mechanical and thermal hyperalgesia were tested by von Frey test or Hargreaves test, respectively."	1.46	CaMKIIα may modulate fentanyl-induced hyperalgesia via a CeLC-PAG-RVM-spinal cord descending facilitative pain pathway in rats. ( Chen, J; Jin, S; Li, Z; Liu, J; Luo, F; Yin, P, 2017)
"Opioid-induced hyperalgesia (OIH) is a less-studied phenomenon that has been reported in both preclinical and clinical studies."	1.43	Inhibition of CaMKIIα in the Central Nucleus of Amygdala Attenuates Fentanyl-Induced Hyperalgesia in Rats. ( Li, C; Li, Z; Luo, F; Wang, ZJ; Yin, P, 2016)
"Fentanyl-induced neurotoxicity is an uncommon adverse effect of fentanyl and is seldom seen in pediatric palliative care practice."	1.42	Fentanyl-Induced Neurotoxicity in Children. ( Deodhar, J; Muckaden, MA; Ostwal, S; Salins, N, 2015)
"Carrageenan-induced hyperalgesia is a widely used pain model in rodents."	1.40	Differential effects of opioid-related ligands and NSAIDs in nonhuman primate models of acute and inflammatory pain. ( Ko, MC; Lee, H; Rice, KC; Sukhtankar, DD, 2014)
"Rats exhibited significant mechanical allodynia following 2 weeks of chronic oxaliplatin administration."	1.40	The contribution of Gi/o protein to opioid antinociception in an oxaliplatin-induced neuropathy rat model. ( Hasegawa, M; Kanbara, T; Kanemasa, T; Mori, T; Nakamura, A; Ogawa, K; Sakaguchi, G; Shibasaki, M; Suzuki, T; Takasu, K, 2014)
"The fentanyl-induced increase in analgesia was minimally affected by a 1."	1.40	Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats. ( Baby, SM; Discala, JF; Gruber, RB; Henderson, F; Lewis, SJ; May, WJ; Puskovic, V; Young, AP, 2014)
"Hyperalgesia is a cardinal symptom of opioid withdrawal."	1.39	Opioid withdrawal increases transient receptor potential vanilloid 1 activity in a protein kinase A-dependent manner. ( Endres-Becker, J; Fischer, O; Schäfer, M; Spahn, V; Stein, C; Zöllner, C, 2013)
"In contrast to the opioid, chronic hyperalgesia did not interfere with the reinforcing effect of food."	1.39	Effect of chronic pain on fentanyl self-administration in mice. ( Fairbanks, CA; Kitto, KF; Krumenacher, P; Peterson, CD; Wade, CL; Wilcox, GL, 2013)
"Von Frey filaments were used to measure mechanical allodynia of the hind paw and abdomen."	1.38	Involvement of spinal orexin A in the electroacupuncture analgesia in a rat model of post-laparotomy pain. ( Feng, XM; Jiang, JW; Mao-Ying, QL; Mi, WL; Wang, YQ; Wang, ZF; Wu, GC; Xia, F; Xiao, S, 2012)
"The patient also developed hyperalgesia, allodynia, and photophobia and became extremely irritable upon handling."	1.38	Suspected opioid-induced hyperalgesia in an infant. ( Chalkiadis, GA; Hallett, BR, 2012)
"Long-lasting hyperalgesia was induced in male Sprague Dawley rats with subcutaneous fentanyl (4 injections, 60 μg/kg per injection at 15-minute intervals) resulting in a total dose of 240 μg/kg."	1.37	The median effective dose of ketamine and gabapentin in opioid-induced hyperalgesia in rats: an isobolographic analysis of their interaction. ( Benhamou, D; Mazoit, JX; Sitbon, P; Van Elstraete, AC, 2011)
"In prestressed rats, fULD-induced hyperalgesia and the exaggerated inflammatory hyperalgesia were prevented NMDA receptor antagonists."	1.37	Endogenous opioids released during non-nociceptive environmental stress induce latent pain sensitization Via a NMDA-dependent process. ( Chateauraynaud, J; Gavello-Baudy, S; Laboureyras, E; Laulin, JP; Le Roy, C; Simonnet, G, 2011)
"Fentanyl-induced hyperalgesia and antinociception after systemic administration has been shown in previous clinical and experimental studies."	1.35	Magnesium modifies fentanyl-induced local antinociception and hyperalgesia. ( Gunay, I; Gunes, Y; Mert, T; Ozcengiz, D, 2009)
"MK-801 blocked and reversed hyperalgesia caused by the acute injection and continuous infusion of fentanyl, respectively, in naltrexone-treated CD-1 mice, indicating the contribution of NMDA receptors to fentanyl hyperalgesia."	1.35	Acute and chronic fentanyl administration causes hyperalgesia independently of opioid receptor activity in mice. ( Arout, C; Caldwell, M; Dahan, A; Kest, B; Waxman, AR, 2009)
"Sevoflurane effects on hyperalgesia were evaluated in Sprague-Dawley rats: opioid-naive rats, rats treated with fentanyl (4 x 60 microg kg(-1)) and rats with inflammatory pain (carrageenan) treated with fentanyl (4 x 60 microg kg(-1))."	1.35	Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in Sprague-Dawley rats. ( Janvier, G; Laulin, JP; Maurette, P; Richebé, P; Rivalan, B; Rivat, C; Simonnet, G, 2009)
"Pain was well controlled."	1.35	Fentanyl-induced neurotoxicity and paradoxic pain. ( George, ML; Okon, TR, 2008)
"Hyperalgesia was induced in male Sprague-Dawley rats with subcutaneous fentanyl (four injections, 20, 60, or 100 microg/kg per injection at 15-min intervals)."	1.35	Gabapentin prevents delayed and long-lasting hyperalgesia induced by fentanyl in rats. ( Benhamou, D; Mazoit, JX; Sitbon, P; Van Elstraete, AC, 2008)
"The opiate tolerance was complicated by tactile hyperalgesia at the site of the surgical wound."	1.35	[Acute opiate tolerance and postoperative hyperalgesia after a brief infusion of remifentanil managed with multimodal analgesia]. ( Cortiñas Sáenz, M; Cortiñas Sáenz, ML; Gerónimo Pardo, M; Hernández Vallecillo, MT; Ibarra Martí, ML; Mateo Cerdán, CM, 2008)
"Fifty percent N2O strongly reduced hyperalgesia induced by a first inflammation and its enhancement by fentanyl, and prevented exaggerated hyperalgesia induced by second inflammatory pain or NNES."	1.34	Nitrous oxide (N2O) prevents latent pain sensitization and long-term anxiety-like behavior in pain and opioid-experienced rats. ( Bessière, B; Contarino, A; Laboureyras, E; Laulin, JP; Richebé, P; Simonnet, G, 2007)
"Differences in postoperative pain sensitivity were assessed by the observational pain measures COMFORT and VAS, and by morphine intake and (nor)epinephrine plasma concentrations."	1.33	Does neonatal surgery lead to increased pain sensitivity in later childhood? ( Anand, KJS; Duivenvoorden, HJ; Peters, JWB; Schouw, R; Tibboel, D; van Dijk, M, 2005)
"In fentanyl-treated rats with inflammatory or incisional pain, nitrous oxide strongly limited both magnitude and duration of hyperalgesia."	1.33	Nitrous oxide revisited: evidence for potent antihyperalgesic properties. ( Creton, C; Laulin, JP; Lemaire, M; Maurette, P; Richebé, P; Rivat, C; Simonnet, G, 2005)
"Subcutaneous fentanyl led to delayed hyperalgesia associated with a decrease in the nociceptive threshold lasting two days (35% decrease for the maximum effect)."	1.33	Protective effect of prior administration of magnesium on delayed hyperalgesia induced by fentanyl in rats. ( Benhamou, D; Conti, M; Mazoit, JX; Sitbon, P; Van Elstraete, AC, 2006)
"Opioid-induced delayed hyperalgesia and allodynia have been reported in human and animal models."	1.33	Opioid-induced hyperalgesia in a murine model of postoperative pain: role of nitric oxide generated from the inducible nitric oxide synthase. ( Cabañero, D; Célérier, E; González, JR; Maldonado, R; Puig, MM, 2006)
"hyperalgesia was unaltered by liposome injection (P > 0."	1.32	Tissue monocytes/macrophages in inflammation: hyperalgesia versus opioid-mediated peripheral antinociception. ( Brack, A; Labuz, D; Machelska, H; Reszka, R; Rittner, HL; Schäfer, M; Schiltz, A; Stein, C, 2004)
"The initial hyperalgesia induced by 0."	1.31	Large-amplitude 5-HT1A receptor activation: a new mechanism of profound, central analgesia. ( Assié, MB; Bardin, L; Carilla-Durand, E; Colpaert, FC; Cosi, C; Koek, W; Pauwels, PJ; Tarayre, JP; Vacher, B; Wiesenfeld-Hallin, Z; Xu, XJ, 2002)
"Ketamine pretreatment, which had no analgesic effect on its own, enhanced the earlier response (analgesia) and prevented the development of long-lasting hyperalgesia."	1.31	Long-lasting hyperalgesia induced by fentanyl in rats: preventive effect of ketamine. ( Célèrier, E; Jun, Y; Larcher, A; Laulin, JP; Reynier, P; Rivat, C; Simonnet, G, 2000)
"The long-lasting hyperalgesia induced by the first carrageenan injection was dose-dependently enhanced in both duration and magnitude in 4 x 60 or 4 x 100 microg/kg fentanyl-treated rats: 5 or 10 days, respectively, as compared with 2 days in saline-treated rats."	1.31	Fentanyl enhancement of carrageenan-induced long-lasting hyperalgesia in rats: prevention by the N-methyl-D-aspartate receptor antagonist ketamine. ( Célèrier, E; Corcuff, JB; Laulin, JP; Pain, L; Rivat, C; Simonnet, G, 2002)
"Ketamine pretreatment (10 mg/kg) increased the fentanyl analgesic effect (4 x 60 microg/kg), suppressed the immediate hyperalgesic phase, and restored the full effect of a subsequent morphine injection."	1.31	The role of ketamine in preventing fentanyl-induced hyperalgesia and subsequent acute morphine tolerance. ( Chauvin, M; Corcuff, JB; Laulin, JP; Maurette, P; Rivat, C; Simonnet, G, 2002)

Research

Studies (110)

Authors

Clinical Trials (12)

Trial Overview

Trial Outcomes

Allodynia as Detected With a Soft Brush in the Periumbilical Region 24 h After the Procedure

Timeframe	Studies, this research(%)	All Research%
pre-1990	1 (0.91)	18.7374
1990's	4 (3.64)	18.2507
2000's	40 (36.36)	29.6817
2010's	52 (47.27)	24.3611
2020's	13 (11.82)	2.80

Authors	Studies
Araldi, D	3
Bonet, IJM	2
Green, PG	1
Levine, JD	3
Wang, XX	1
Cui, LL	1
Gan, SF	1
Zhang, ZR	1
Xiao, J	1
Li, CH	2
Luo, F	6
Kim, Y	1
Bae, H	1
Yoo, S	1
Park, SK	1
Lim, YJ	1
Sakura, S	1
Kim, JT	1
Bai, T	1
Chen, H	1
Hu, W	1
Liu, J	2
Lin, X	1
Chen, S	1
Yang, X	1
Chen, J	3
Li, C	2
Efune, PN	1
Rebstock, SE	1
Puig, S	1
Shelton, MA	1
Barko, K	1
Seney, ML	1
Logan, RW	1
Wang, X	1
Gan, S	1
Zhang, Z	2
Zhu, P	1
Zhou, X	1
Li, Q	1
Luo, Q	3
Wang, L	1
Xiong, Y	1
Wu, G	1
Chang, L	5
Liu, P	1
Shu, H	4
Manohar, S	1
Adler, HJ	1
Radziwon, K	1
Salvi, R	1
Baamonde, A	1
Menéndez, L	1
González-Rodríguez, S	1
Lastra, A	1
Seitz, V	1
Stein, C	3
Machelska, H	2
Khomula, EV	2
Uddin, O	1
Jenne, C	1
Fox, ME	1
Arakawa, K	1
Keller, A	1
Cramer, N	1
Quillet, R	2
Schneider, S	3
Utard, V	2
Drieu la Rochelle, A	1
Elhabazi, K	3
Henningsen, JB	1
Gizzi, P	1
Schmitt, M	4
Kugler, V	1
Simonneaux, V	2
Ilien, B	2
Simonin, F	4
Bihel, F	4
Li, Z	2
Yin, P	2
Jin, S	1
Nguyen, T	1
Decker, AM	1
Langston, TL	1
Mathews, KM	1
Siemian, JN	1
Li, JX	1
Harris, DL	1
Runyon, SP	1
Zhang, Y	1
Ye, F	3
Tao, Y	1
Ferrari, LF	1
Srinivas, NR	1
Li, QB	1
Luo, QH	1
Tao, YX	1
Shu, HH	1
Wang, Z	1
Wang, Y	1
Xia, Z	1
Shinohara, A	1
Andoh, T	1
Saiki, I	1
Kuraishi, Y	1
Rangappa, S	1
Rangan, KK	1
Sudarshan, TS	1
Murthy, SN	1
Kalaydjian, A	1
Farah, F	1
Cheng, Y	2
Acquadro, MA	1
Gerges, FJ	1
Kars, MS	1
Villacres Mori, B	1
Ahn, S	1
Merwin, S	1
Wendolowski, S	1
Gecelter, R	1
Rothman, A	1
Poon, S	1
Welzing, L	1
Link, F	1
Junghaenel, S	1
Oberthuer, A	1
Harnischmacher, U	1
Stuetzer, H	1
Roth, B	1
Kontrimavičiūtė, E	1
Sipylaitė, J	1
Aksionova, D	1
Cincilevičiūtė, G	1
Brimas, G	1
Michel-Lauter, B	1
Bernardy, K	1
Schwarzer, A	1
Nicolas, V	1
Maier, C	1
Sukhtankar, DD	1
Lee, H	1
Rice, KC	1
Ko, MC	2
Wade, CL	1
Krumenacher, P	1
Kitto, KF	1
Peterson, CD	1
Wilcox, GL	1
Fairbanks, CA	1
Henderson, F	1
May, WJ	1
Gruber, RB	1
Discala, JF	1
Puskovic, V	1
Young, AP	1
Baby, SM	1
Lewis, SJ	1
Aoki, Y	1
Mizoguchi, H	1
Watanabe, C	1
Sakurada, T	1
Sakurada, S	1
Tanaka, K	1
Nakanishi, Y	1
Sekino, S	1
Ikegami, M	1
Ikeda, H	1
Kamei, J	1
Kanbara, T	1
Nakamura, A	2
Takasu, K	1
Ogawa, K	1
Shibasaki, M	1
Mori, T	1
Suzuki, T	2
Hasegawa, M	1
Sakaguchi, G	1
Kanemasa, T	1
Yildirim, V	1
Doganci, S	1
Cinar, S	1
Eskin, MB	1
Ozkan, G	1
Eksert, S	1
Ince, ME	1
Dogrul, A	1
Humbert, JP	2
Bertin, I	2
Wagner, P	1
Laboureyras, E	6
Petit-Demoulière, B	3
Schneider, E	2
Mollereau, C	2
Simonnet, G	11
Bourguignon, JJ	3
Marcus, DJ	1
Zee, M	1
Hughes, A	1
Yuill, MB	1
Hohmann, AG	1
Mackie, K	1
Guindon, J	1
Morgan, DJ	1
Lyons, PJ	1
Rivosecchi, RM	1
Nery, JP	1
Kane-Gill, SL	1
Ostwal, S	1
Salins, N	1
Deodhar, J	1
Muckaden, MA	1
Mauermann, E	2
Filitz, J	2
Dolder, P	1
Rentsch, KM	1
Bandschapp, O	2
Ruppen, W	2
You, HJ	1
Lei, J	1
Xiao, Y	1
Ye, G	1
Sun, ZH	1
Yang, L	2
Niu, N	1
Dmytriyev, DV	2
Konoplytskyi, VS	2
Wang, ZJ	1
Kong, M	1
Li, J	1
Zhong, Z	1
Wu, Z	1
Guo, R	1
Blum, CA	1
Lurati Buse, G	1
Ben Boujema, M	1
Ancel, C	1
Beltramo, M	1
Bucher, B	1
Sorg, T	1
Meziane, H	2
Bujalska, M	1
Malinowska, E	1
Makulska-Nowak, H	1
Gumułka, SW	1
Kouvaras, E	1
Asprodini, EK	1
Asouchidou, I	1
Vasilaki, A	1
Kilindris, T	1
Michaloudis, D	1
Koukoutianou, I	1
Papatheodoropoulos, C	1
Kostopoulos, G	1
Pranevicius, M	1
Pranevicius, O	1
Richebé, P	5
Rivalan, B	1
Rivat, C	6
Laulin, JP	8
Janvier, G	1
Maurette, P	3
Waxman, AR	1
Arout, C	1
Caldwell, M	1
Dahan, A	1
Kest, B	1
Chateauraynaud, J	2
Mert, T	1
Gunes, Y	1
Ozcengiz, D	1
Gunay, I	1
Greer, JJ	1
Ren, J	1
Fernández-Dueñas, V	1
Ciruela, F	1
Gandía, J	1
Sánchez, S	1
Planas, E	1
Poveda, R	1
Andresen, T	3
Upton, RN	1
Foster, DJ	1
Christrup, LL	1
Arendt-Nielsen, L	3
Drewes, AM	3
Staahl, C	1
Oksche, A	2
Mansikka, H	2
Van Elstraete, AC	3
Sitbon, P	3
Benhamou, D	3
Mazoit, JX	3
Saunders, DL	1
Messina, J	1
Darwish, M	1
Xie, F	1
Leary, KJ	1
Cantilena, LR	1
Trigo, JM	1
Moulédous, L	1
Zajac, JM	1
Bockel, F	1
Maldonado, R	2
Le Roy, C	2
Gavello-Baudy, S	1
Narita, M	1
Imai, S	1
Ozeki, A	1
Asato, M	1
Rahmadi, M	1
Sudo, Y	1
Hojo, M	1
Uezono, Y	1
Devi, LA	1
Kuzumaki, N	1
Tramullas, M	1
Dinan, TG	1
Cryan, JF	1
Hallett, BR	1
Chalkiadis, GA	1
Wei, X	1
Wei, W	1
Malver, LP	1
Tröster, A	1
Ihmsen, H	1
Singler, B	1
Koppert, W	3
Juba, KM	1
Wahler, RG	1
Daron, SM	1
Feng, XM	1
Mi, WL	1
Xia, F	1
Mao-Ying, QL	1
Jiang, JW	1
Xiao, S	1
Wang, ZF	1
Wang, YQ	1
Wu, GC	1
Mousa, SA	1
Shaqura, M	1
Khalefa, BI	1
Zöllner, C	2
Schaad, L	1
Schneider, J	1
Shippenberg, TS	1
Richter, JF	1
Hellweg, R	1
Shakibaei, M	1
Schäfer, M	3
Spahn, V	1
Fischer, O	1
Endres-Becker, J	1
Price, DD	1
Staud, R	1
Robinson, ME	1
Mauderli, AP	1
Cannon, R	1
Vierck, CJ	1
Colpaert, FC	1
Tarayre, JP	1
Koek, W	1
Pauwels, PJ	1
Bardin, L	1
Xu, XJ	1
Wiesenfeld-Hallin, Z	1
Cosi, C	1
Carilla-Durand, E	1
Assié, MB	1
Vacher, B	1
Kang, YJ	1
Vincler, M	1
Li, X	2
Conklin, D	1
Eisenach, JC	1
Katz, J	2
Cohen, L	2
Schmid, R	1
Chan, VW	1
Wowk, A	1
Inan, UU	1
Sivaci, RG	1
Ermis, SS	1
Oztürk, F	1
Maegawa, FA	1
Tonussi, CR	1
Brack, A	1
Labuz, D	1
Schiltz, A	1
Rittner, HL	1
Reszka, R	1
Peters, JWB	1
Schouw, R	1
Anand, KJS	1
van Dijk, M	1
Duivenvoorden, HJ	1
Tibboel, D	1
Gaitán, G	1
Ahuir, FJ	1
Herrero, JF	1
Creton, C	1
Lemaire, M	1
Célérier, E	3
González, JR	1
Cabañero, D	1
Puig, MM	1
Guntz, E	1
Talla, G	1
Roman, A	1
Dumont, H	1
Segers, B	1
Sosnowski, M	1
Baad-Hansen, L	1
Juhl, GI	1
Jensen, TS	1
Brandsborg, B	1
Svensson, P	1
Conti, M	1
Robertson, LJ	1
Drummond, PD	1
Hammond, GR	1
Schmelz, M	2
Bessière, B	1
Contarino, A	1
Davis, MP	1
Shaiova, LA	1
Angst, MS	2
Lenz, H	1
Raeder, J	1
Hoymork, SC	1
Okon, TR	1
George, ML	1
Cortiñas Sáenz, M	1
Gerónimo Pardo, M	1
Cortiñas Sáenz, ML	1
Hernández Vallecillo, MT	1
Ibarra Martí, ML	1
Mateo Cerdán, CM	1
Welsh, EM	1
Nolan, AM	1
Tverskoy, M	1
Oz, Y	1
Isakson, A	1
Finger, J	1
Bradley, EL	1
Kissin, I	1
Bruera, E	1
Pereira, J	1
Zeck, S	1
Blunk, JA	1
Likar, R	1
Sittl, R	1
Tuchman, JE	1
Johnson, MD	1
Wiesenauer, K	1
Woods, JH	1
Jun, Y	1
Larcher, A	1
Reynier, P	1
Ta, LE	1
Dionne, RA	1
Fricton, JR	1
Hodges, JS	1
Kajander, KC	1
Cooper, DW	1
Clark, JD	1
Corcuff, JB	2
Pain, L	1
Chauvin, M	1
Joris, JL	1
Dubner, R	1
Hargreaves, KM	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Effect of a Perioperative Opioid Free Anesthesia-Analgesia (OFA-A) Strategy on Surgical Stress Response in Elective Open Abdominal Aortic Aneurysm Repair: A Prospective Randomized Study[NCT04894864]	Phase 4	40 participants (Anticipated)	Interventional	2020-10-08	Recruiting
Effect of Intraoperative and Post-operative Opioids on Persistent Opioid Use in the Surgical Patient[NCT03367988]	Phase 2/Phase 3	100 participants (Anticipated)	Interventional	2018-12-01	Recruiting
Can Fentanyl Lead to Opioid-induced Hyperalgesia in Healthy Volunteers? A Prospective, Randomized, Double-blinded Crossover Study[NCT02252458]		21 participants (Actual)	Interventional	2014-08-31	Completed
Effect of Fentanyl on Expression of Main Opioid Receptor (OPRM1) on Human Granulosa Cells During Ultrasound-guided Transvaginal Oocyte Retrieval.[NCT03248076]		30 participants (Anticipated)	Observational	2017-04-01	Recruiting
Contribution of COMT Haplotypes in Propranolol Analgesic Efficacy for Treating Post-surgical Pain After Laparoscopic Hemicolectomy[NCT02511483]	Phase 2	10 participants (Actual)	Interventional	2015-05-18	Terminated (stopped due to Difficulty with recruitment)
Effect of High-dose Target-controlled Naloxone Infusion on Pain and Hyperal-gesia in Patients Following Recovery From Impacted Mandibular Third Molar Extraction. A Randomized, Placebo-controlled, Double-blind Crossover Study.[NCT02976337]	Phase 2	14 participants (Anticipated)	Interventional	2017-10-12	Recruiting
Phenomics and Genomics of Clinically Relevant Chronic Postsurgical Pain: A Multicenter Prospective Study[NCT04798573]		10,000 participants (Anticipated)	Observational	2012-08-03	Active, not recruiting
Evaluation of the Effect of Ketamine on Remifentanil-induced Hyperalgesia Using Filaments, an Algometer, and Interleukins: a Double-blind, Randomized Study[NCT01301079]	Phase 3	60 participants (Actual)	Interventional	2010-09-30	Completed
Personalizing Perioperative Morphine Analgesia for Adolescents Undergoing Major Spine Surgeries[NCT01839461]		137 participants (Actual)	Observational	2009-07-31	Completed
STTEPP: Safety, Tolerability and Dose Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis[NCT05603702]	Phase 1	24 participants (Anticipated)	Interventional	2023-03-17	Recruiting
Fentanyl Ultra Low Doses Effects on Human Volunteer's Nociceptive Threshold. Towards a Simple Pharmacological Test Able to Predict Pain Vulnerability, Post Operative Hyperalgesia Development Risk?[NCT00454259]	Phase 4	48 participants (Actual)	Interventional	2007-03-31	Completed
Effect of Beta Blockade on Opioid-Induced Hyperalgesia in Humans[NCT01222091]	Phase 2	10 participants (Actual)	Interventional	2009-02-28	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The evaluations using the soft brush were performed 2-3 cm from the incision in the periumbilical region (where the large trocar was placed) 24 h after the procedure (NCT01301079)
Timeframe: 24 h after the procedure

Allodynia as Detected With a Soft Brush in the Periumbilical Region Before the Procedure

Intervention	participants (Number)
Ketamine	1
Saline	0

The evaluations using the soft brush were performed 2-3 cm from the incision in the periumbilical region (where the large trocar was placed) before the procedure (NCT01301079)
Timeframe: Before the procedure (Baseline)

Allodynia as Detected With a Soft Brush in the Thenar Eminence 24 h After the Procedure

Intervention	participants (Number)
Ketamine	1
Saline	0

The evaluations using the soft brush were performed in the thenar eminence of the non dominant hand 24 h after the procedure (NCT01301079)
Timeframe: 24 h after the procedure

Allodynia as Detected With a Soft Brush in the Thenar Eminence Before the Procedure

Intervention	participants (Number)
Ketamine	1
Saline	3

The evaluations using the soft brush were performed in the thenar eminence of the nondominant hand before the procedure (NCT01301079)
Timeframe: Before the procedure (Baseline)

Extension of Hyperalgesia

Intervention	participants (Number)
Ketamine	1
Saline	0

The 300-g filament was used 24 hours after the operation to induce a stimulus and delineate the extent of hyperalgesia from the periumbilical region. The stimulus was started outside the periumbilical region, where no pain sensation was reported, and continued every 0.5 cm until the 4 points of the periumbilical scar were reached (top, right side, left side, and bottom). The first point where the patient complained of pain was marked. If no pain sensation was reported, the stimulus was terminated 0.5 cm from the incision. The distance of each point from the surgical incision was measured, and the sum of the distances of the points was determined. (NCT01301079)
Timeframe: 24 hours after the procedure

Hyperalgesia in the Postoperative Period as Measured With Algometer in the Periumbilical Region

Intervention	centimeter (Mean)
Ketamine	10.61
Saline	11.82

The mechanical pain threshold was evaluated using an algometer. The pressure was increased by 0.1 kgf/second until the patient complained of pain. The mean of three determinations was calculated. (NCT01301079)
Timeframe: 24 h after the procedure

Hyperalgesia in the Postoperative Period as Measured With Algometer in Thenar Eminence

Intervention	kilogram force/second (Mean)
Ketamine	3.5
Saline	3.7

Hyperalgesia in the Postoperative Period as Measured With Monofilaments in the Periumbilical Region

Intervention	kilogram force/second (Mean)
Ketamine	0.56
Saline	0.51

The pain threshold was assessed using six von Frey monofilaments (0,05 g; 0,2 g; 2 g; 4 g; 10 g e 300 g) in the periumbilical region in the postoperative period (24h after the procedure). The use of different von Frey monofilaments, starting with the lightest and ending with the heaviest, was separated by at least 30 seconds to reduce any anticipated responses due to a new stimulation that was performed too soon after the preceding stimulation. Three assessments were made for each monofilament, and this was considered positive when the patient responded to two of the determinations for each monofilament. (NCT01301079)
Timeframe: 24h after the procedure

Hyperalgesia in the Postoperative Period as Measured With Monofilaments in Thenar Eminence

Intervention	gram (Mean)
Ketamine	248
Saline	205

The pain threshold was assessed using six von Frey monofilaments (0,05 g; 0,2 g; 2 g; 4 g; 10 g e 300 g) in thenar eminence in the postoperative period (24 hours after procedure). The use of different von Frey monofilaments, starting with the lightest and ending with the heaviest, was separated by at least 30 seconds to reduce any anticipated responses due to a new stimulation that was performed too soon after the preceding stimulation. Three assessments were made for each monofilament, and this was considered positive when the patient responded to two of the determinations for each monofilament. (NCT01301079)
Timeframe: 24 hours after procedure

Hyperalgesia in the Preoperative Period as Measured With Algometer in the Periumbilical Region

Intervention	gram (Mean)
Ketamine	290
Saline	247

Hyperalgesia in the Preoperative Period as Measured With Algometer in Thenar Eminence

Intervention	kilogram force/second (Mean)
Ketamine	3.6
Saline	3.9

Hyperalgesia in the Preoperative Period as Measured With Monofilaments in the Periumbilical Region

Intervention	kilogram force/second (Mean)
Ketamine	2.51
Saline	2.19

The pain threshold was assessed using six von Frey monofilaments (0,05 g; 0,2 g; 2 g; 4 g; 10 g e 300 g) in the periumbilical region in the preoperative period. The use of different von Frey monofilaments, starting with the lightest and ending with the heaviest, was separated by at least 30 seconds to reduce any anticipated responses due to a new stimulation that was performed too soon after the preceding stimulation. Three assessments were made for each monofilament, and this was considered positive when the patient responded to two of the determinations for each monofilament. (NCT01301079)
Timeframe: Before the procedure (Baseline)

Hyperalgesia in the Preoperative Period as Measured With Monofilaments in Thenar Eminence

Intervention	gram (Mean)
Ketamine	279
Saline	269

The pain threshold was assessed using six von Frey monofilaments (0,05 g; 0,2 g; 2 g; 4 g; 10 g e 300 g) in thenar eminence in the preoperative period. The use of different von Frey monofilaments, starting with the lightest and ending with the heaviest, was separated by at least 30 seconds to reduce any anticipated responses due to a new stimulation that was performed too soon after the preceding stimulation. Three assessments were made for each monofilament, and this was considered positive when the patient responded to two of the determinations for each monofilament. (NCT01301079)
Timeframe: Before the procedure (Baseline)

Morphine Consumption Within 24 h

Pain 12 Hours

Intervention	gram (Mean)
Ketamine	300
Saline	300

Intervention	milligram (Mean)
Ketamine	27.40
Saline	27.70

The scale measure pain after 12 hours (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. (NCT01301079)
Timeframe: 12 hours

Pain 120 Minutes

Intervention	units on a scale (Mean)
Ketamine	1.6
Saline	1.4

The scale measure pain after 120 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. (NCT01301079)
Timeframe: 120 minutes

Pain 150 Minutes

Intervention	units on a scale (Mean)
Ketamine	2.2
Saline	2.0

The scale measure pain after 150 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. (NCT01301079)
Timeframe: 150 minutes

Pain 18 Hours

Intervention	units on a scale (Mean)
Ketamine	1.4
Saline	1.4

The scale measure pain after 18 hours (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. (NCT01301079)
Timeframe: 18 hours

Pain 180 Minutes

Intervention	units on a scale (Mean)
Ketamine	1.5
Saline	1.3

The scale measure pain after 180 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. (NCT01301079)
Timeframe: 180 minutes

Pain 210 Minutes

Intervention	units on a scale (Mean)
Ketamine	1.1
Saline	1.3

The scale measure pain after 210 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. (NCT01301079)
Timeframe: 210 minutes

Pain 24 Hours

Intervention	units on a scale (Mean)
Ketamine	0.9
Saline	1.2

The scale measure pain after 24 hours (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. (NCT01301079)
Timeframe: 24 hours

Pain 240 Minutes

Intervention	units on a scale (Mean)
Ketamine	1.4
Saline	0.8

The scale measure pain after 240 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. (NCT01301079)
Timeframe: 240 minutes

Pain 30 Minutes

Intervention	units on a scale (Mean)
Ketamine	1.0
Saline	1.1

The scale measure pain after 30 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. (NCT01301079)
Timeframe: 30 minutes

Pain 6 Hours

Intervention	units on a scale (Mean)
Ketamine	5.5
Saline	6.2

The scale measure pain after 6 hours (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. (NCT01301079)
Timeframe: 6 hours

Pain 60 Minutes

Intervention	units on a scale (Mean)
Ketamine	0.9
Saline	0.7

The scale measure pain after 60 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. (NCT01301079)
Timeframe: 60 minutes

Pain 90 Minutes

Intervention	units on a scale (Mean)
Ketamine	4.6
Saline	5.1

The scale measure pain after 90 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. (NCT01301079)
Timeframe: 90 minutes

Serum Level of Interleukin (IL)-10 24 h After the Procedure

Intervention	units on a scale (Mean)
Ketamine	3.4
Saline	3.4

Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 24 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. (NCT01301079)
Timeframe: 24 h after the procedure

Serum Level of Interleukin (IL)-10 5h After the Procedure

Intervention	picogram/milliliter (Mean)
Ketamine	8.6
Saline	5.0

Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 5 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-10 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. (NCT01301079)
Timeframe: 5h after the procedure

Serum Level of Interleukin (IL)-10 Before the Procedure

Intervention	picogram/milliliter (Mean)
Ketamine	9.1
Saline	5.5

Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes before the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. (NCT01301079)
Timeframe: Baseline (Before the procedure)

Serum Level of Interleukin (IL)-6 24 h After the Procedure

Intervention	picogram/milliliter (Mean)
Ketamine	7.8
Saline	1.9

Serum Level of Interleukin (IL)-6 5 h After the Procedure

Intervention	picogram/milliliter (Mean)
Ketamine	24.1
Saline	24.8

Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 5 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. (NCT01301079)
Timeframe: 5 h after the procedure

Serum Level of Interleukin (IL)-6 Before the Procedure

Intervention	picogram/milliliter (Mean)
Ketamine	29.3
Saline	34.8

Serum Level of Interleukin (IL)-8 24 h After the Procedure

Intervention	picogram/milliliter (Mean)
Ketamine	3.3
Saline	2.1

Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 24 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-8 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. (NCT01301079)
Timeframe: 24 h after the procedure

Serum Level of Interleukin (IL)-8 5 h After the Procedure

Intervention	picogram/milliliter (Mean)
Ketamine	6.0
Saline	4.5

Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 5 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-8 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. (NCT01301079)
Timeframe: 5 h after the procedure

Serum Level of Interleukin (IL)-8 Before the Procedure

Intervention	picogram/milliliter (Mean)
Ketamine	8.0
Saline	11.3

Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes before the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-8 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. (NCT01301079)
Timeframe: Baseline (Before the procedure)

Time to First Morphine Supplementation

Objective Opioid Withdrawal Scale (OOWS)

Intervention	picogram/milliliter (Mean)
Ketamine	3.3
Saline	2.2

Intervention	minutes (Median)
Ketamine	18
Saline	15

OOWS: Is a 13-item instrument of documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. Maximum score = 13, minimum score = 0. Lower scores correspond to fewer symptoms. (NCT01222091)
Timeframe: Pretreatment [90 min prior to 60-min REM infusion]; 30 min prior to 60-min REM infusion; 15 and 40 min after start of 60-min REM infusion; 5, 15, and 75 minutes after finish of 60-min REM infusion)

Percent Change From Baseline in Size (Area) of Secondary Hyperalgesia After Cessation of Remifentanil Infusion, a Measure of Opioid-induced Hyperalgesia (OIH).

Intervention	units on a scale (Mean)
	Pretreatment	30 min prior to REM infusion	15 min after start of REM infusion	40 min after start of REM infusion	5 minutes after finish of REM infusion	15 minutes after finish of REM infusion	75 minutes after finish of REM infusion
Placebo	1.1	1.1	0.8	0.5	1.8	2.1	1.6
Propranolol	1.2	1.1	0.1	0.8	3	2.8	1.7

A slightly modified version of a previously described model of secondary hyperalgesia was used. Two copper wires contained in a microdialysis catheter were inserted in parallel over a length of 5 mm into the dermis of the right volar forearm. The wires were connected to a constant current stimulator controlled by a pulse generator to deliver rectangular and monophasic pulses with a duration of 0.5 mg at 2 Hz. Over a period of 15 min, the current was increased by targeting a pain rating of 5 on an 11-point numeric rating scale (0 = no pain and 10 = maximum tolerable pain) until the hyperalgesic area surrounding the stimulation site was fully established. Once the area was established, the current was held constant. Percent change from baseline in size (area) of secondary hyperalgesia after cessation of remifentanil infusion was calculated per group. (NCT01222091)
Timeframe: Baseline; 15 min post remifentanil (REM) infusion; 60 min post REM infusion

Article	Year
Fentanyl-induced hyperalgesia in acute pain management. Journal of pain & palliative care pharmacotherapy, 2015, Volume: 29, Issue:2 Topics: Acute Pain; Analgesics, Opioid; Fentanyl; Humans; Hyperalgesia; Pain Management	2015
The impact of opioid-induced hyperalgesia for postoperative pain. Best practice & research. Clinical anaesthesiology, 2007, Volume: 21, Issue:1 Topics: Alfentanil; Analgesics, Opioid; Animals; Fentanyl; Humans; Hyperalgesia; Morphine; Pain, Postoperati	2007

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Effect of remifentanil on post-operative analgesic consumption in patients undergoing shoulder arthroplasty after interscalene brachial plexus block: a randomized controlled trial. Journal of anesthesia, 2022, Volume: 36, Issue:4 Topics: Analgesics; Analgesics, Opioid; Arthroplasty, Replacement, Shoulder; Brachial Plexus Block; Delirium	2022
Remifentanil-induced tolerance, withdrawal or hyperalgesia in infants: a randomized controlled trial. RAPIP trial: remifentanil-based analgesia and sedation of paediatric intensive care patients. Neonatology, 2013, Volume: 104, Issue:1 Topics: Analgesia; Analgesics, Opioid; Drug Tolerance; Fentanyl; Gestational Age; Humans; Hyperalgesia; Hypn	2013
Comparison of different anesthetic regimens in patients undergoing laparoscopic adjustable gastric banding operations: a prospective randomized trial. Medicina (Kaunas, Lithuania), 2012, Volume: 48, Issue:12 Topics: Adult; Aged; Analgesics, Opioid; Anesthetics, Intravenous; Clinical Protocols; Female; Fentanyl; Gas	2012
Acute high dose-fentanyl exposure produces hyperalgesia and tactile allodynia after coronary artery bypass surgery. European review for medical and pharmacological sciences, 2014, Volume: 18, Issue:22 Topics: Aged; Analgesics, Opioid; Coronary Artery Bypass; Female; Fentanyl; Humans; Hyperalgesia; Male; Midd	2014
Does Fentanyl Lead to Opioid-induced Hyperalgesia in Healthy Volunteers?: A Double-blind, Randomized, Crossover Trial. Anesthesiology, 2016, Volume: 124, Issue:2 Topics: Adult; Analgesics, Opioid; Cold Temperature; Cross-Over Studies; Dose-Response Relationship, Drug; D	2016
Does Fentanyl Lead to Opioid-induced Hyperalgesia in Healthy Volunteers?: A Double-blind, Randomized, Crossover Trial. Anesthesiology, 2016, Volume: 124, Issue:2 Topics: Adult; Analgesics, Opioid; Cold Temperature; Cross-Over Studies; Dose-Response Relationship, Drug; D	2016
Does Fentanyl Lead to Opioid-induced Hyperalgesia in Healthy Volunteers?: A Double-blind, Randomized, Crossover Trial. Anesthesiology, 2016, Volume: 124, Issue:2 Topics: Adult; Analgesics, Opioid; Cold Temperature; Cross-Over Studies; Dose-Response Relationship, Drug; D	2016
Does Fentanyl Lead to Opioid-induced Hyperalgesia in Healthy Volunteers?: A Double-blind, Randomized, Crossover Trial. Anesthesiology, 2016, Volume: 124, Issue:2 Topics: Adult; Analgesics, Opioid; Cold Temperature; Cross-Over Studies; Dose-Response Relationship, Drug; D	2016
Low-dose butorphanol alleviates remifetanil-induced hyperalgesia in patients undergoing laparoscopic cholecystectomy. Journal of clinical anesthesia, 2016, Volume: 34 Topics: Adult; Analgesics, Opioid; Anesthesia, General; Butorphanol; Cholecystectomy, Laparoscopic; Double-B	2016
Time course of copeptin during a model of experimental pain and hyperalgesia: A randomised volunteer crossover trial. European journal of anaesthesiology, 2017, Volume: 34, Issue:5 Topics: Adult; Analgesics, Opioid; Biomarkers; Cross-Over Studies; Double-Blind Method; Fentanyl; Glycopepti	2017
Pharmacokinetic/pharmacodynamic relationships of transdermal buprenorphine and fentanyl in experimental human pain models. Basic & clinical pharmacology & toxicology, 2011, Volume: 108, Issue:4 Topics: Adult; Analgesics, Opioid; Buprenorphine; Capsaicin; Cold Temperature; Cross-Over Studies; Dose-Resp	2011
Effect of transdermal opioids in experimentally induced superficial, deep and hyperalgesic pain. British journal of pharmacology, 2011, Volume: 164, Issue:3 Topics: Administration, Cutaneous; Analgesics; Analgesics, Opioid; Buprenorphine; Capsaicin; Cross-Over Stud	2011
Assessment of the relative potency of fentanyl buccal tablet to intravenous morphine in healthy volunteers using a thermally induced hyperalgesia pain model. Journal of clinical pharmacology, 2012, Volume: 52, Issue:6 Topics: Administration, Buccal; Adolescent; Adult; Analgesics, Opioid; Anesthetics, Intravenous; Anesthetics	2012
A double-blind, placebo-controlled study on the effect of buprenorphine and fentanyl on descending pain modulation: a human experimental study. The Clinical journal of pain, 2012, Volume: 28, Issue:7 Topics: Administration, Cutaneous; Adult; Analgesics, Opioid; Buprenorphine; Cross-Over Studies; Double-Blin	2012
Interaction of fentanyl and buprenorphine in an experimental model of pain and central sensitization in human volunteers. The Clinical journal of pain, 2012, Volume: 28, Issue:8 Topics: Adult; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Cross-Over Studies; Double-Blind Met	2012
Enhanced temporal summation of second pain and its central modulation in fibromyalgia patients. Pain, 2002, Volume: 99, Issue:1-2 Topics: Adult; Analgesics, Opioid; Cold Temperature; Female; Fentanyl; Fibromyalgia; Hot Temperature; Humans	2002
Postoperative morphine use and hyperalgesia are reduced by preoperative but not intraoperative epidural analgesia: implications for preemptive analgesia and the prevention of central sensitization. Anesthesiology, 2003, Volume: 98, Issue:6 Topics: Adaptation, Psychological; Adult; Affect; Analgesia, Epidural; Analgesia, Patient-Controlled; Analge	2003
Effects of fentanyl on pain and hemodynamic response after retrobulbar block in patients having phacoemulsification. Journal of cataract and refractive surgery, 2003, Volume: 29, Issue:6 Topics: Adult; Aged; Analgesia; Anesthesia, Local; Anesthetics, Combined; Anesthetics, Intravenous; Anesthet	2003
Preventive analgesia is associated with reduced pain disability 3 weeks but not 6 months after major gynecologic surgery by laparotomy. Anesthesiology, 2004, Volume: 101, Issue:1 Topics: Adaptation, Psychological; Adult; Affect; Analgesia; Analgesics, Opioid; Anesthesia, General; Anesth	2004
Differential effect of intravenous S-ketamine and fentanyl on atypical odontalgia and capsaicin-evoked pain. Pain, 2007, Volume: 129, Issue:1-2 Topics: Adult; Analgesics; Analysis of Variance; Area Under Curve; Capsaicin; Case-Control Studies; Double-B	2007
Administration of fentanyl before remifentanil-based anaesthesia has no influence on post-operative pain or analgesic consumption. Acta anaesthesiologica Scandinavica, 2008, Volume: 52, Issue:1 Topics: Acetaminophen; Adolescent; Adult; Aged; Analgesia, Patient-Controlled; Analgesics; Anesthesia, Intra	2008
Effects of non-steroidal anti-inflammatory drugs on the hyperalgesia to noxious mechanical stimulation induced by the application of a tourniquet to a forelimb of sheep. Research in veterinary science, 1994, Volume: 57, Issue:3 Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Clonixin; Cross-Over Studies; Disease	1994
Preemptive effect of fentanyl and ketamine on postoperative pain and wound hyperalgesia. Anesthesia and analgesia, 1994, Volume: 78, Issue:2 Topics: Adult; Analgesia; Double-Blind Method; Female; Fentanyl; Humans; Hyperalgesia; Ketamine; Middle Aged	1994
The effects of intradermal fentanyl and ketamine on capsaicin-induced secondary hyperalgesia and flare reaction. Anesthesia and analgesia, 1999, Volume: 89, Issue:6 Topics: Adult; Analgesics; Analgesics, Opioid; Axons; Capsaicin; Erythema; Female; Fentanyl; Humans; Hyperal	1999

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Contribution of G-Protein α-Subunits to Analgesia, Hyperalgesia, and Hyperalgesic Priming Induced by Subanalgesic and Analgesic Doses of Fentanyl and Morphine. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2022, 02-16, Volume: 42, Issue:7 Topics: Analgesia; Analgesics, Opioid; Animals; Fentanyl; GTP-Binding Protein alpha Subunits; Hyperalgesia;	2022
Inhibition of Oligodendrocyte Apoptosis in the Prelimbic Medial Prefrontal Cortex Prevents Fentanyl-induced Hyperalgesia in Rats. The journal of pain, 2022, Volume: 23, Issue:6 Topics: Analgesics, Opioid; Animals; Apoptosis; Fentanyl; Hyperalgesia; Oligodendroglia; Pain; Prefrontal Co	2022
Amygdala Metabotropic Glutamate Receptor 1 Influences Synaptic Transmission to Participate in Fentanyl-Induced Hyperalgesia in Rats. Cellular and molecular neurobiology, 2023, Volume: 43, Issue:3 Topics: Amygdala; Analgesics, Opioid; Animals; Fentanyl; Hyperalgesia; Rats; Rats, Sprague-Dawley; Receptors	2023
Suspected opioid-induced hyperalgesia in an infant following surgery: A case report. Journal of clinical pharmacy and therapeutics, 2022, Volume: 47, Issue:9 Topics: Adult; Analgesics, Opioid; Fentanyl; Humans; Hyperalgesia; Infant; Ketamine; Male; Pain	2022
Sex-specific role of the circadian transcription factor NPAS2 in opioid tolerance, withdrawal and analgesia. Genes, brain, and behavior, 2022, Volume: 21, Issue:7 Topics: Analgesia; Analgesics; Analgesics, Opioid; Animals; Basic Helix-Loop-Helix Transcription Factors; Dr	2022
HCN-Channel-Dependent Hyperexcitability of the Layer V Pyramidal Neurons in IL-mPFC Contributes to Fentanyl-Induced Hyperalgesia in Male Rats. Molecular neurobiology, 2023, Volume: 60, Issue:5 Topics: Animals; Fentanyl; Hyperalgesia; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Male;	2023
A single dose of ketamine relieves fentanyl-induced-hyperalgesia by reducing inflammation initiated by the TLR4/NF-κB pathway in rat spinal cord neurons. Drug discoveries & therapeutics, 2023, Sep-15, Volume: 17, Issue:4 Topics: Animals; Cyclooxygenase 2; Fentanyl; Hyperalgesia; Inflammation; Ketamine; Neurons; NF-kappa B; Rats	2023
Interaction of auditory and pain pathways: Effects of stimulus intensity, hearing loss and opioid signaling. Hearing research, 2020, Volume: 393 Topics: Analgesics, Opioid; Animals; Auditory Threshold; Deafness; Fentanyl; Hearing Loss; Hearing Loss, Noi	2020
A low pKa ligand inhibits cancer-associated pain in mice by activating peripheral mu-opioid receptors. Scientific reports, 2020, 10-29, Volume: 10, Issue:1 Topics: Analgesics, Opioid; Animals; Bone Neoplasms; Cancer Pain; Cell Line, Tumor; Fentanyl; Hydrogen-Ion C	2020
Opioid-Induced Hyperalgesic Priming in Single Nociceptors. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021, 01-06, Volume: 41, Issue:1 Topics: Analgesics, Opioid; Animals; Deoxyadenosines; Dinoprostone; Fentanyl; Hyperalgesia; Lectins; Male; M	2021
Divergent profiles of fentanyl withdrawal and associated pain in mice and rats. Pharmacology, biochemistry, and behavior, 2021, Volume: 200 Topics: Analgesics, Opioid; Animals; Behavior, Animal; Female; Fentanyl; Humans; Hyperalgesia; Locomotion; M	2021
Identification of an Journal of medicinal chemistry, 2021, 06-10, Volume: 64, Issue:11 Topics: Analgesics, Opioid; Animals; Cricetinae; Dipeptides; Female; Fentanyl; Half-Life; Humans; Hyperalges	2021
CaMKIIα may modulate fentanyl-induced hyperalgesia via a CeLC-PAG-RVM-spinal cord descending facilitative pain pathway in rats. PloS one, 2017, Volume: 12, Issue:5 Topics: Analgesics, Opioid; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Central Amygdaloid	2017
Discovery of Novel Proline-Based Neuropeptide FF Receptor Antagonists. ACS chemical neuroscience, 2017, 10-18, Volume: 8, Issue:10 Topics: Analgesics, Opioid; Animals; Blood-Brain Barrier; Fentanyl; Hyperalgesia; Narcotic Antagonists; Olig	2017
Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats. Anesthesia and analgesia, 2018, Volume: 126, Issue:1 Topics: Analgesics, Opioid; Animals; Cytokines; Fentanyl; Ganglia, Spinal; Hyperalgesia; Inflammation Mediat	2018
Fentanyl Induces Rapid Onset Hyperalgesic Priming: Type I at Peripheral and Type II at Central Nociceptor Terminals. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018, 02-28, Volume: 38, Issue:9 Topics: Analgesics, Opioid; Animals; Calcium Signaling; Fentanyl; Hyperalgesia; Male; Neuronal Plasticity; N	2018
Lack of Translatable Proinflammatory Cytokines in Cerebrospinal Fluid in Rats With Increased Hyperalgesia With or Without Fentanyl Treatment. Anesthesia and analgesia, 2018, Volume: 126, Issue:6 Topics: Animals; Cytokines; Fentanyl; Ganglia, Spinal; Hyperalgesia; Rats; Spinal Cord	2018
In Response. Anesthesia and analgesia, 2018, Volume: 126, Issue:6 Topics: Animals; Cytokines; Fentanyl; Ganglia, Spinal; Hyperalgesia; Rats; Spinal Cord	2018
Role of spinal cyclooxygenase-2 and prostaglandin E2 in fentanyl-induced hyperalgesia in rats. British journal of anaesthesia, 2018, Volume: 120, Issue:4 Topics: Analgesics, Opioid; Animals; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Dose-Response R	2018
Effects of three forms of local anesthesia on perioperative fentanyl-induced hyperalgesia. Bioscience trends, 2018, May-13, Volume: 12, Issue:2 Topics: Anesthesia, Local; Animals; Disease Models, Animal; Fentanyl; Ganglia, Spinal; Humans; Hyperalgesia;	2018
Analgesic effects of systemic fentanyl on cancer pain are mediated by not only central but also peripheral opioid receptors in mice. European journal of pharmacology, 2018, Aug-15, Volume: 833 Topics: Action Potentials; Analgesics, Opioid; Animals; Cancer Pain; Cell Line, Tumor; Disease Models, Anima	2018
Antiallodynic and Antihyperalgesic Activities of Fentanyl-Loaded Dermal Clay Dressings in Rat Model of Second-Degree Burn Injury. Journal of pharmaceutical sciences, 2018, Volume: 107, Issue:10 Topics: Animals; Bandages; Burns; Clay; Disease Models, Animal; Fentanyl; Hyperalgesia; Male; Pain; Rats; Ra	2018
Opioid Induced Hyperalgesia with Intrathecal Infusion of High-Dose Fentanyl. Pain practice : the official journal of World Institute of Pain, 2019, Volume: 19, Issue:2 Topics: Analgesics, Opioid; Bupivacaine; Female; Fentanyl; Humans; Hyperalgesia; Infusion Pumps, Implantable	2019
Fentanyl versus remifentanil-based TIVA for pediatric scoliosis repair: does it matter? Regional anesthesia and pain medicine, 2019, Volume: 44, Issue:6 Topics: Adolescent; Analgesics, Opioid; Anesthesia, General; Anesthesia, Intravenous; Child; Drug Tolerance;	2019
[Role of mGluR5 in laterocapcular division of central nucleus of amygdala in fentanyl-induced hyperalgesia in rats]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences, 2019, Apr-28, Volume: 44, Issue:4 Topics: Animals; Central Amygdaloid Nucleus; Fentanyl; Hyperalgesia; Male; Rats; Rats, Sprague-Dawley; Recep	2019
[Dependency syndrome and hyperalgesia due to an opioid therapy for curative treatable pain. Case report of an apparent palliative patient]. Schmerz (Berlin, Germany), 2013, Volume: 27, Issue:5 Topics: Activities of Daily Living; Administration, Cutaneous; Administration, Intranasal; Aged; Analgesics,	2013
Differential effects of opioid-related ligands and NSAIDs in nonhuman primate models of acute and inflammatory pain. Psychopharmacology, 2014, Volume: 231, Issue:7 Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Acute Pain	2014
Effect of chronic pain on fentanyl self-administration in mice. PloS one, 2013, Volume: 8, Issue:11 Topics: Animals; Behavior, Animal; Chronic Pain; Female; Fentanyl; Hyperalgesia; Male; Mice; Motor Activity;	2013
Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats. Respiratory physiology & neurobiology, 2014, Jan-15, Volume: 191 Topics: Analysis of Variance; Animals; Blood Gas Analysis; Blood Pressure; Body Temperature; Consciousness;	2014
Differential alternation of the antinociceptive effect of narcotic analgesics on the inflammatory pain state. Neuroscience letters, 2014, Feb-07, Volume: 560 Topics: Animals; Fentanyl; Freund's Adjuvant; Hyperalgesia; Inflammation; Male; Methadone; Mice; Narcotics;	2014
Fentanyl produces an anti-hyperalgesic effect through the suppression of sodium channels in mice with painful diabetic neuropathy. European journal of pharmacology, 2014, Jun-15, Volume: 733 Topics: Analgesics, Opioid; Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Dose-Response R	2014
The contribution of Gi/o protein to opioid antinociception in an oxaliplatin-induced neuropathy rat model. Journal of pharmacological sciences, 2014, Volume: 126, Issue:3 Topics: Analgesics; Analgesics, Opioid; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; F	2014
Development of a peptidomimetic antagonist of neuropeptide FF receptors for the prevention of opioid-induced hyperalgesia. ACS chemical neuroscience, 2015, Mar-18, Volume: 6, Issue:3 Topics: Analgesics, Opioid; Animals; Arginine; Chemical Phenomena; Cyclic AMP; Fentanyl; HEK293 Cells; Human	2015
Tolerance to the antinociceptive effects of chronic morphine requires c-Jun N-terminal kinase. Molecular pain, 2015, Jun-12, Volume: 11 Topics: Analgesics; Animals; Anthracenes; Cisplatin; Drug Tolerance; Fentanyl; Formaldehyde; Hyperalgesia; H	2015
Fentanyl-Induced Neurotoxicity in Children. Journal of pain & palliative care pharmacotherapy, 2015, Volume: 29, Issue:4 Topics: Akathisia, Drug-Induced; Analgesics, Opioid; Child; Female; Fentanyl; Hallucinations; Headache; Huma	2015
Pre-emptive analgesia and its supraspinal mechanisms: enhanced descending inhibition and decreased descending facilitation by dexmedetomidine. The Journal of physiology, 2016, Apr-01, Volume: 594, Issue:7 Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Dexmedetomidine; Fentanyl; Hyperalgesia; Imid	2016
[MORPHOLOGICAL CHANGES OF SKIN IN OPERATIVE WOUND IN SYNDROME OF OPIOID-INDUCED HYPERALGESIA]. Klinichna khirurhiia, 2015, Issue:10 Topics: Abdominal Cavity; Abdominal Neoplasms; Administration, Cutaneous; Adolescent; Analgesics, Opioid; Ch	2015
Inhibition of CaMKIIα in the Central Nucleus of Amygdala Attenuates Fentanyl-Induced Hyperalgesia in Rats. The Journal of pharmacology and experimental therapeutics, 2016, Volume: 359, Issue:1 Topics: Animals; Benzylamines; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Central Amygdaloid Nucleu	2016
[PROPHYLAXIS OF POSTOPERATIVE HYPERALGESIA, BASED ON MORPHOLOGICAL SUBSTANTIATION OF THE ANALGESIA METHOD]. Klinichna khirurhiia, 2016, Issue:3 Topics: Abdominal Muscles; Abdominal Neoplasms; Adolescent; Analgesia, Epidural; Analgesics, Opioid; Child;	2016
RF313, an orally bioavailable neuropeptide FF receptor antagonist, opposes effects of RF-amide-related peptide-3 and opioid-induced hyperalgesia in rodents. Neuropharmacology, 2017, 05-15, Volume: 118 Topics: Administration, Oral; Analgesics, Opioid; Animals; CHO Cells; Cricetinae; Cricetulus; Disease Models	2017
Magnesium ions and opioid agonist activity in streptozotocin-induced hyperalgesia. Pharmacology, 2008, Volume: 82, Issue:3 Topics: Analgesics, Opioid; Animals; Buprenorphine; Diabetes Mellitus, Experimental; Diabetic Neuropathies;	2008
Fentanyl treatment reduces GABAergic inhibition in the CA1 area of the hippocampus 24 h after acute exposure to the drug. Neuropharmacology, 2008, Volume: 55, Issue:7 Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Analgesics, Opioid; Animals; Bicu	2008
Non-opioid anesthesia with esmolol avoids opioid-induced hyperalgesia and reduces fentanyl requirement after laparoscopy. Anesthesia and analgesia, 2009, Volume: 108, Issue:3 Topics: Adrenergic beta-Antagonists; Analgesics, Opioid; Anesthesia; Fentanyl; Humans; Hyperalgesia; Laparos	2009
Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in Sprague-Dawley rats. Canadian journal of anaesthesia = Journal canadien d'anesthesie, 2009, Volume: 56, Issue:2 Topics: Analgesics, Opioid; Anesthetics, Inhalation; Animals; Carrageenan; Disease Models, Animal; Dose-Resp	2009
Acute and chronic fentanyl administration causes hyperalgesia independently of opioid receptor activity in mice. Neuroscience letters, 2009, Oct-02, Volume: 462, Issue:1 Topics: Analysis of Variance; Animals; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Fentanyl; Hot	2009
Long-term pain vulnerability after surgery in rats: prevention by nefopam, an analgesic with antihyperalgesic properties. Anesthesia and analgesia, 2009, Volume: 109, Issue:2 Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Carrageenan; Chronic Disease; Fentanyl; Hyper	2009
Magnesium modifies fentanyl-induced local antinociception and hyperalgesia. Naunyn-Schmiedeberg's archives of pharmacology, 2009, Volume: 380, Issue:5 Topics: Analgesics, Opioid; Animals; Drug Interactions; Drug Synergism; Female; Fentanyl; Hot Temperature; H	2009
Ampakine therapy to counter fentanyl-induced respiratory depression. Respiratory physiology & neurobiology, 2009, Aug-31, Volume: 168, Issue:1-2 Topics: Animals; Animals, Newborn; Disease Models, Animal; Drug Administration Schedule; Fentanyl; Heart Rat	2009
Histamine H3 receptor activation potentiates peripheral opioid-mediated antinociception: substance P role in peripheral inflammation in mice. European journal of pharmacology, 2010, Jul-25, Volume: 638, Issue:1-3 Topics: Analgesics; Animals; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Fe	2010
The median effective dose of ketamine and gabapentin in opioid-induced hyperalgesia in rats: an isobolographic analysis of their interaction. Anesthesia and analgesia, 2011, Volume: 113, Issue:3 Topics: Amines; Analgesics; Analgesics, Opioid; Analysis of Variance; Animals; Cyclohexanecarboxylic Acids;	2011
Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments. British journal of pharmacology, 2012, Volume: 165, Issue:2 Topics: Adamantane; Analgesics, Opioid; Animals; Behavior, Animal; Conditioning, Classical; Dipeptides; Drug	2012
Endogenous opioids released during non-nociceptive environmental stress induce latent pain sensitization Via a NMDA-dependent process. The journal of pain, 2011, Volume: 12, Issue:10 Topics: Analgesics, Opioid; Analysis of Variance; Animals; Carrageenan; Disease Models, Animal; Excitatory A	2011
Possible involvement of prolonging spinal µ-opioid receptor desensitization in the development of antihyperalgesic tolerance to µ-opioids under a neuropathic pain-like state. Addiction biology, 2013, Volume: 18, Issue:4 Topics: Analgesics, Opioid; Animals; beta-Endorphin; Dose-Response Relationship, Drug; Drug Tolerance; Femal	2013
Chronic psychosocial stress induces visceral hyperalgesia in mice. Stress (Amsterdam, Netherlands), 2012, Volume: 15, Issue:3 Topics: Adrenal Glands; Analgesics, Opioid; Animals; Anxiety; Atropine; Body Weight; Chronic Disease; Colon;	2012
Suspected opioid-induced hyperalgesia in an infant. British journal of anaesthesia, 2012, Volume: 108, Issue:1 Topics: Abdominal Wall; Analgesics, Non-Narcotic; Analgesics, Opioid; Anesthetics, Dissociative; Dexmedetomi	2012
Role of gabapentin in preventing fentanyl- and morphine-withdrawal-induced hyperalgesia in rats. Journal of anesthesia, 2012, Volume: 26, Issue:2 Topics: Amines; Analgesics, Opioid; Animals; Chronic Pain; Cyclohexanecarboxylic Acids; Drug Tolerance; Fent	2012
Morphine and hydromorphone-induced hyperalgesia in a hospice patient. Journal of palliative medicine, 2013, Volume: 16, Issue:7 Topics: Adult; Analgesics, Opioid; Carcinoma, Non-Small-Cell Lung; Delayed-Action Preparations; Female; Fent	2013
Involvement of spinal orexin A in the electroacupuncture analgesia in a rat model of post-laparotomy pain. BMC complementary and alternative medicine, 2012, Nov-22, Volume: 12 Topics: Abdomen; Acupuncture Points; Analgesia; Animals; Electroacupuncture; Fentanyl; Hindlimb; Hyperalgesi	2012
Rab7 silencing prevents μ-opioid receptor lysosomal targeting and rescues opioid responsiveness to strengthen diabetic neuropathic pain therapy. Diabetes, 2013, Volume: 62, Issue:4 Topics: Analgesics, Opioid; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Neuropathies;	2013
Opioid withdrawal increases transient receptor potential vanilloid 1 activity in a protein kinase A-dependent manner. Pain, 2013, Volume: 154, Issue:4 Topics: Analgesics, Opioid; Animals; Calcium; Capsaicin; Cells, Cultured; Cyclic AMP; Cyclic AMP-Dependent P	2013
Large-amplitude 5-HT1A receptor activation: a new mechanism of profound, central analgesia. Neuropharmacology, 2002, Volume: 43, Issue:6 Topics: Acetates; Adrenergic Uptake Inhibitors; Amines; Aminopyridines; Analgesia; Analgesics; Animals; Cell	2002
Intrathecal ketorolac reverses hypersensitivity following acute fentanyl exposure. Anesthesiology, 2002, Volume: 97, Issue:6 Topics: Anesthetics, Intravenous; Animals; Cyclooxygenase Inhibitors; Drug Hypersensitivity; Fentanyl; Hyper	2002
The L-arginine/nitric oxide/cyclic-GMP pathway apparently mediates the peripheral antihyperalgesic action of fentanyl in rats. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas, 2003, Volume: 36, Issue:12 Topics: Analgesics, Opioid; Animals; Arginine; Cyclic GMP; Dinoprostone; Dose-Response Relationship, Drug; F	2003
Tissue monocytes/macrophages in inflammation: hyperalgesia versus opioid-mediated peripheral antinociception. Anesthesiology, 2004, Volume: 101, Issue:1 Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Clodronic Acid; Fentanyl; Flow Cytometry; Foo	2004
Does neonatal surgery lead to increased pain sensitivity in later childhood? Pain, 2005, Volume: 114, Issue:3 Topics: Analgesics, Opioid; Child, Preschool; Cross-Sectional Studies; Female; Fentanyl; Follow-Up Studies;	2005
Enhancement of fentanyl antinociception by subeffective doses of nitroparacetamol (NCX-701) in acute nociception and in carrageenan-induced monoarthritis. Life sciences, 2005, May-20, Volume: 77, Issue:1 Topics: Acetaminophen; Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-	2005
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Opioid-induced hyperalgesia in a murine model of postoperative pain: role of nitric oxide generated from the inducible nitric oxide synthase. Anesthesiology, 2006, Volume: 104, Issue:3 Topics: Analgesics, Opioid; Animals; Fentanyl; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Nitric Oxide; N	2006
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Intervention	percentage of change (Number)
	15 min post remifentanil infusion	60 min post remifentanil infusion
Placebo	-34	141.5
Propranolol	-28	-19

fentanyl and Allodynia