dextrorphan has been researched along with Pain* in 13 studies
2 review(s) available for dextrorphan and Pain
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The Origin, Expression, Function and Future Research Focus of a G Protein-coupled Receptor, Mas-related Gene X2 (MrgX2).
Mas-related genes (Mrgs) belong to a large family of G protein-coupled receptor genes found in rodents. Human MRGX proteins are G protein-coupled 7-transmembrane proteins sharing 41-52% amino acid identity with each other, but have no orthologs in rodents. MrgX2 is a member of the MrgX family. MRGX2 is expressed in the small neurons of sensory ganglia and mast cells. It can interact with a series of factors and genes such as the peptides substance P, vasoactive intestinal peptide, cortistatin (CST), proadrenomedullin N-terminal peptide (PAMP), LL-37, PMX-53 and β-defensins. MRGX2 is related to nociception, adrenal gland secretion and mast cell degranulation. Recent research on MrgX2 provides insights into its role in nociception and anti-microbial activities. This article reviewed the origin, expression and function of MrgX2, and discussed possible future research focus. Topics: Adrenomedullin; Cell Degranulation; Dextrorphan; Evolution, Molecular; Ganglia, Sensory; Gene Expression Regulation; Humans; Mast Cells; Nerve Tissue Proteins; Neuropeptides; Nociception; Pain; Protein Isoforms; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Signal Transduction; Substance P; Vasoactive Intestinal Peptide | 2015 |
Neurophysiology of opioid poorly responsive pain.
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. The loss of opioid receptors is likely to be important where peripheral nerve pathology or compression occurs, but the evidence suggests that increasing the dose will overcome the reduced opioid response. Morphine-3-glucuronide is unlikely to be a factor, nor is dynorphin, but the endogenous peptides CCK and F8Fa may be important. Finally, there is an association between the NMDA receptor and hyperalgesia/allodynia and reduced opioid sensitivity. Dextrorphan and ketamine reduce NMDA mediated events and so are available to test this hypothesis. Topics: Analgesics, Opioid; Animals; Central Nervous System; Clonidine; Dextromethorphan; Dextrorphan; Dynorphins; Humans; Morphine; N-Methylaspartate; Neoplasms; Neurophysiology; Neuroprotective Agents; Pain; Rats; Receptors, N-Methyl-D-Aspartate; Receptors, Opioid; Sympatholytics | 1994 |
2 trial(s) available for dextrorphan and Pain
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Intravenous dextromethorphan to human volunteers: relationship between pharmacokinetics and anti-hyperalgesic effect.
The aim of this study was to investigate the effect of dextromethorphan (DM) 0.5 mg/kg administered intravenously (i.v.) on hyperalgesia and pain after a tissue injury in human volunteers, and to describe the relationship between pharmacokinetic and pharmacodynamic data. The heat-capsaicin sensitisation model, a well-established experimental hyperalgesia model was induced in 24 healthy, male volunteers aged 21-35 years. The subjects received i.v. DM 0.5 mg/kg or isotonic saline on two separate study sessions. The primary outcome measure from 0 to 3 h was reduction in area of established secondary hyperalgesia. Secondary outcome measures were reduction in area of secondary hyperalgesia in response to brief thermal stimulation, heat pain detection thresholds and painfulness after tonic heat pain. Blood samples were collected throughout the study to describe the relationship between pharmacokinetic and pharmacodynamic data. Intravenous DM 0.5 mg/kg significantly reduced areas of established secondary hyperalgesia with an average of 39% (P<0.05). Development of secondary hyperalgesia was substantially prevented by DM (P<0.05). No significant effect was seen on either heat pain detection thresholds or after tonic heat pain. The pharmacokinetic-pharmacodynamic relationship showed a large inter-subject variation with a mean delay in effect of nearly 2 h in relation to peak serum concentration. The results strongly indicate that DM is an anti-hyperalgesic drug. The delay in effect may be explained by several mechanisms and suggests that timing of DM administration is an essential factor for using the drug in clinical settings. Topics: Adolescent; Adult; Area Under Curve; Capsaicin; Cross-Over Studies; Dextromethorphan; Dextrorphan; Double-Blind Method; Excitatory Amino Acid Antagonists; Humans; Hyperalgesia; Infusions, Intravenous; Male; Pain; Pain Measurement; Pain Threshold; Reaction Time; Time Factors; Treatment Outcome | 2005 |
Assessment of the effect of dextromethorphan and ketamine on the acute nociceptive threshold and wind-up of the second pain response in healthy male volunteers.
The aim of this study was to assess the efficacy of dextromethorphan and ketamine relative to placebo on the acute nociceptive threshold and wind-up of second pain response in healthy male volunteers.. The trial was a randomized, double-blind, placebo-controlled, three period crossover, double dummy design in 12 healthy male volunteers. During each of the three periods (which were separated by a 1 week washout period) each volunteer received either a single oral dose of 0.7 mg kg(-1) dextromethorphan and placebo to ketamine, or placebo to dextromethorphan followed by a single intravenous injection of 0.375 mg kg(-1) ketamine, or placebo to both dextromethorphan and ketamine. The trial did not schedule administration of both ketamine and dextromethorphan together. Acute nociceptive thresholds and wind-up of second pain were measured in the skin of the thenar eminence of the ventral surfaces of the right and left hands, using a SOMEDIC thermotest apparatus, before and at the estimated tmax for dextromethorphan (i.e. 2.15 h). Blood pressure and heart rate were also monitored before dosing and after the dosing regimen.. Neither dextromethorphan nor ketamine had any significant effect on acute nociceptive thresholds on either hand (P>0.05). Moreover, dextromethorphan was without any significant effect (P>0.05) on the wind-up of the second pain response on either hand. The lsmean number of stimuli tolerated vs placebo (95% confidence intervals of the difference in number of stimuli in parentheses) were 15.84 vs 16.48 (-5.52, 4.24) and 11.75 vs 15.25 (-11.89, 4.90) for left- and right-hand, respectively, following dextromethorphan administration. In contrast ketamine produced significant reductions in wind-up to second pain in both the left and right hands (P=0.0002 and 0.0386, respectively). The lsmean numbers of stimuli tolerated vs placebo (95% confidence intervals of the difference in number of stimuli in parentheses) were 28.41 vs 16.48 (6.60, 17.25) and 25.00 vs 15.25 (0.58, 18.93) for left- and right-hand, respectively.. Wind-up of second pain induced by noxious heat is sensitive to intervention by ketamine, which is known to block the NMDA receptor. These data infer that the wind-up phenomenon evoked by noxious heat involves the activation of NMDA receptors. This volunteer model of pain may have utility in the evaluation of agents that modulate their antinociceptive actions via NMDA mechanisms. Topics: Acute Disease; Adult; Analgesics; Cross-Over Studies; Dextromethorphan; Dextrorphan; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Excitatory Amino Acid Antagonists; Humans; Injections, Intravenous; Ketamine; Male; Middle Aged; Nociceptors; Pain; Pain Threshold; Receptors, N-Methyl-D-Aspartate | 2002 |
9 other study(ies) available for dextrorphan and Pain
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Clonidine as adjuvant for oxybuprocaine, bupivacaine or dextrorphan has a significant peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats.
The aim of the study was to evaluate co-administration of clonidine with oxybuprocaine (ester type), bupivacaine (amide type) or dextrorphan (non-ester or non-amide type) and to see whether it could have a peripheral action in enhancing local anesthesia on infiltrative cutaneous analgesia in rats. Cutaneous analgesia was evaluated by a block of the cutaneous trunci muscle reflex (CTMR) in response to local dorsal cutaneous noxious pinprick in rats. The analgesic effect of the addition of clonidine with oxybuprocaine, bupivacaine or dextrorphan by subcutaneous injection was evaluated. On an ED(50) basis, the rank of drug potency was oxybuprocaine>bupivacaine>dextrorphan (P<0.01). Mixtures of clonidine (0.12μmol) with oxybuprocaine, bupivacaine or dextrorphan (ED(50) or ED(95)) extended the duration of action and increased the potency on infiltrative cutaneous analgesia. Among these drugs, the addition of clonidine to bupivacaine (amide type) elicits the most effective cutaneous analgesia. Clonidine at the dose of 0.12 and 0.24μmol did not produce cutaneous analgesia. Oxybuprocaine showed more potent cutaneous analgesia than bupivacaine or dextrorphan in rats. Co-administration of oxybuprocaine, bupivacaine or dextrorphan with clonidine increased the potency and duration on infiltrative cutaneous analgesia. The addition of clonidine to bupivacaine (amide type) elicits more effective cutaneous analgesia than oxybuprocaine (ester type) or dextrorphan (non-ester or non-amide type). Topics: Adjuvants, Anesthesia; Adrenergic alpha-Agonists; Analgesia; Anesthetics, Local; Animals; Area Under Curve; Bupivacaine; Clonidine; Data Interpretation, Statistical; Dextrorphan; Dose-Response Relationship, Drug; Drug Synergism; Excitatory Amino Acid Antagonists; Injections, Subcutaneous; Male; Pain; Peripheral Nerves; Physical Stimulation; Procaine; Rats; Rats, Sprague-Dawley | 2011 |
The spinal anaesthetic effect of dextromethorphan, dextrorphan, and 3-methoxymorphinan.
Dextromethorphan, an antitussive, has a complex pharmacologic profile and has not been well studied. Our aim was to evaluate whether dextromethorphan and its metabolites, dextrorphan and 3-methoxymorphinan, have a spinal anaesthetic effect. Using a method of spinal blockade in rats, we evaluated the potencies and durations of the effects of dextromethorphan and its metabolites on spinal blockades of motor function and nociception. Bupivacaine was the active control. We found that dextromethorphan and its metabolites produced a dose-related spinal blockade of motor function and nociception. On an ED(50) basis, the ranks of potencies were bupivacaine>dextrorphan>3-methoxymorphinan>dextromethorphan (p<0.05 for the differences). On an equipotent basis, dextrorphan and bupivacaine produced similarly longer nociceptive blockades than did dextromethorphan and 3-methoxymorphinan (p<0.05 for the differences). Co-administration of dextromethorphan or its metabolites with bupivacaine produced an additive effect. In conclusion, intrathecal injections of dextromethorphan or its metabolites, dextrorphan and 3-methoxymorphinan, produced dose-related spinal blockades of motor function and nociception. The suitability of these drugs as clinical spinal anaesthetics is worth further evaluation. Topics: Anesthesia, Spinal; Anesthetics, Local; Animals; Bupivacaine; Dextromethorphan; Dextrorphan; Dose-Response Relationship, Drug; Drug Synergism; Excitatory Amino Acid Antagonists; Male; Motor Activity; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Time Factors | 2007 |
Intraplantar injection of dextrorphan, ketamine or memantine attenuates formalin-induced behaviors.
The possible prophylactic effects of local injection of NMDA receptor antagonists that are currently used in humans was investigated in the present study. Intraplantar pretreatment with either 5 mM dextrorphan (DEX), 10 mM memantine (MEM) or 10 mM ketamine (KET) significantly attenuated formalin-induced lifting and licking behaviors, however flinching behavior was not effected. Control experiments indicated that these drug actions could be attributed to local and not systemic effects of the antagonists. We hypothesize that these actions result from blocking NMDA receptors present on unmyelinated sensory axons in the skin. These data suggest that peripheral NMDA receptors contribute to nociceptor activation and can be manipulated to reduce pain of peripheral origin. Since DEX, MEM and KET are currently used in humans and considered clinically safe, they have potential therapeutic value in the treatment of physiologic or pathologic pain states which are induced or maintained by peripheral nociceptor activity. Topical or local application would avoid the side effects that can accompany systemic or intrathecal injection of NMDA antagonists. Topics: Animals; Dextrorphan; Foot; Formaldehyde; Injections, Intradermal; Ketamine; Male; Memantine; Motor Activity; Pain; Rats; Rats, Sprague-Dawley; Stereotyped Behavior | 1998 |
Efficacy of spinal NMDA receptor antagonism in formalin hyperalgesia and nerve injury evoked allodynia in the rat.
Neuropathic pain remains a significant clinical problem. Current understanding implicates the spinal cord dorsal horn N-methyl-d-aspartate (NMDA) receptor apparatus in its pathogenesis. Previous reports have described NMDA antagonist reduction of nerve injury-induced thermal hyperalgesia and formalin injection-related electrical activity. We examined a panel of spinally administered NMDA antagonists in two models: allodynia evoked by tight ligation of the fifth and sixth lumbar spinal nerves (a model of chronic nerve injury pain), and the formalin paw test (a model wherein pretreatment with drug may preempt the development of a pain state). A wide range of efficacies was observed. In the nerve injury model, order of efficacy (expressed as percent of maximum possible effect +/- S.E.), at the maximum dose not yielding motor impairment, was memantine (96 +/- 5%) = AP5 (91 +/- 7%) > dextrorphan (64 +/- 11%) = dextromethorphan (65 +/- 22%) > MK801 (34 +/- 8%) > ketamine (18 +/- 6%). For the formalin test, the order of efficacy was AP5 (86 +/- 9%) > memantine (74 +/- 5%) > or = MK801 (67 +/- 16%) > dextrorphan (47 +/- 16%) > dextromethorphan (31 +/- 12%) > ketamine (17 +/- 15%). In the nerve injury model, no supraspinal action was seen after intracerebroventricular injections of dextromethorphan and ketamine. NMDA antagonists by the spinal route appear to be useful therapeutic agents for chemically induced facilitated pain as well as nerve injury induced tactile allodynia. It is not known what accounts for the wide range of efficacies. Topics: 2-Amino-5-phosphonovalerate; Analgesics; Animals; Dextromethorphan; Dextrorphan; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Formaldehyde; Hyperalgesia; Injections, Spinal; Ketamine; Male; Memantine; Morphine; Pain; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Spinal Cord; Spinal Nerves; Touch | 1997 |
Neuropathic pain sensations are differentially sensitive to dextrorphan.
Rats with an experimental painful peripheral neuropathy (the CCI model) display heat-hyperalgesia and mechanoallodynia. Previous work has shown that the heat-hyperalgesia is suppressed by dextrorphan (DEX) and other N-methyl-D-aspartate (NMDA) receptor antagonists. The present work shows that when tested in the same rats, a dose of DEX that is maximally effective against heat-hyperalgesia has no effect on mechano-allodynia. The results suggest that different kinds of abnormal pain sensations may be caused by different pathophysiologic mechanisms that may respond differently to drug therapy. Topics: Animals; Dextrorphan; Hot Temperature; Hyperalgesia; Male; Pain; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Sciatic Nerve | 1994 |
Intrathecal treatment with dextrorphan or ketamine potently reduces pain-related behaviors in a rat model of peripheral mononeuropathy.
The therapeutic effects of dextrorphan and ketamine, two non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, on neuropathic pain-related behaviors were examined in rats with peripheral mononeuropathy induced by loose ligation of the common sciatic nerve (chronic constrictive injury, CCI). Four daily intrathecal treatments (beginning 1 h after nerve ligation) with dextrorphan or ketamine (12.5-100 nmol) reliably attenuated hyperalgesia to radiant heat and spontaneous pain-related behaviors in CCI rats. Thermal hyperalgesia also was reduced in CCI rats receiving a single intrathecal treatment with either dextrorphan or ketamine (50 and 100 nmol for each compound) on day 3 after nerve ligation when thermal hyperalgesia was well developed. Since both dextrorphan and ketamine are currently utilized in other clinical applications, the results suggest a new therapeutic utility of these 'old' compounds in treatment of neuropathic pain syndromes resulting from peripheral nerve injury. Topics: Animals; Behavior, Animal; Dextrorphan; Injections, Spinal; Ketamine; Male; Pain; Pain Measurement; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; Sciatic Nerve | 1993 |
Dextrorphan relieves neuropathic heat-evoked hyperalgesia in the rat.
Dextrorphan (DEX), a non-competitive NMDA receptor antagonist, was given intraperitoneally and intrathecally (i.t.) to rats with an experimental painful peripheral mononeuropathy. The neuropathy was created by placing loosely constrictive ligatures around the sciatic nerve, and the pain threshold was studied with the paw-flick method. The effects of DEX on the neuropathic heat-evoked hyperalgesia that follows this nerve injury were determined during the period of peak symptom severity. DEX given i.p. relieved heat-evoked hyperalgesia in a dose-dependent manner without producing motor impairment. The highest doses tested (12.5 and 25 mg/kg) produced a large but incomplete block (about 50%). DEX had no effect on the responsiveness of the paw on the control side. i.t. injection of 20 micrograms DEX completely blocked heat-hyperalgesia when tested 1 h later; again, the effect was achieved without motor impairment and without any change on the control side. These results suggest that DEX may be useful in the treatment of human neuropathic pain. Topics: Animals; Dextrorphan; Dose-Response Relationship, Drug; Hot Temperature; Injections, Intraperitoneal; Injections, Spinal; Pain; Pain Threshold; Peripheral Nervous System Diseases; Rats; Reaction Time; Sciatic Nerve | 1993 |
Opiates suppress carrageenan-induced edema and hyperthermia at doses that inhibit hyperalgesia.
This study determined whether opiates alter vascular components of inflammation (hyperthermia, edema and plasma extravasation) in addition to the suppression of hyperalgesia. Rats were administered carrageenan into one hind paw and saline into the other hind paw, followed by i.p. injection of morphine (0.2-5.0 mg/kg) or saline at 60 min, and testing at 90 min after hind paw injections. Morphine produced a dose-dependent reduction in carrageenan-induced hyperalgesia (17-53%), hyperthermia (39-53%) and edema (24-36%). Morphine treatment did not alter the temperatures of the contralateral saline-injected paws, indicating that opiate suppression of hyperthermia was not confounded by alterations in systemic body temperature or blood flow. The opiate effects on inflammation were stereospecific since levorphanol (1 mg/kg), but not dextrorphan (1 mg/kg), suppressed carrageenan-evoked hyperalgesia, hyperthermia and edema. Pre-treatment with naltrexone (1.5 mg/kg) blocked the effects of a 5 mg/kg dose of morphine sulfate on hyperalgesia, hyperthermia and edema. In a separate study, i.v. injection of morphine sulfate (2 mg/kg) reduced plasma extravasation by 41% (P less than 0.01). Morphine administration resulted in significantly greater increases in paw withdrawal latencies in the inflamed (38-139%) than the contralateral, saline-treated paws (4-19%). The results indicate that opiates exert a moderate, though significant, reduction in the vascular signs of inflammation in addition to their reduction of hyperalgesia. The mechanisms for this vascular effect involve inhibition of both vasodilation (as indicated by a decrease in hyperthermia) and inhibition of vascular permeability. In addition, opiates exhibit enhanced antinociceptive effects in inflamed paws, even when compared to uninjured paws in the same animal. Topics: Analgesics; Animals; Body Temperature; Carrageenan; Dextrorphan; Dose-Response Relationship, Drug; Edema; Levorphanol; Male; Morphine; Naltrexone; Narcotics; Pain; Rats; Rats, Inbred Strains; Stereoisomerism | 1990 |
The effect of morphine and some other narcotic analgesics on brain tryptophan concentrations.
An acute dose of morphine increased brain tryptophan in mice. This effect was not prevented by naloxone nor was it produced by other narcotic analgesics. Dextrorphan, but not levorphanol, had a similar effect to morphine. A large dose of tryptophan had no effect on the antinociceptive action of morphine in mice. Morphine increased brain tryptophan in rats. This effect was prevented by naloxone. A large dose of tryptophan antagonised the antinociceptive action of morphine in the rat. Topics: Analgesics, Opioid; Animals; Brain; Dextrorphan; Female; Levorphanol; Mice; Morphine; Naloxone; Pain; Tryptophan | 1979 |