Articles: hyperalgesia.
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J. Pharmacol. Exp. Ther. · Feb 1997
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. ⋯ 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.
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Comparative Study
Multiple receptors involved in peripheral alpha 2, mu, and A1 antinociception, tolerance, and withdrawal.
We examined the interactions among three classes of peripherally-acting antinociceptive agents (mu-opioid, alpha 2-adrenergic, and A1-adenosine) in the development of tolerance and dependence to their antinociceptive effects. Antinociception was determined by assessing the degree of inhibition of prostaglandin E2 (PGE2)-induced mechanical hyperalgesia, using the Randall-Selitto paw-withdrawal test. Tolerance developed within 4 hr to the antinociceptive effect of the alpha 2-adrenergic agonist clonidine; dependence also occurred at that time, demonstrated as a withdrawal hyperalgesia that was precipitated by the alpha 2-receptor antagonist yohimbine. ⋯ In conclusion, these data suggest that peripheral antinociception induced by mu, alpha 2, and A1 agonists requires the physical presence of multiple receptors. We propose that there is a mu, A1, alpha 2 receptor complex mediating antinociception in the periphery. In addition, there is cross-tolerance and cross-dependence between mu, A1, and alpha 2 antinociception, suggesting that their underlying mechanisms are related.
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Patients with complex regional pain syndrome (CRPS) (n=20) were examined in order to evaluate cutaneous reactions to norepinephrine (NE) on both the affected and the unaffected limb in comparison to healthy controls. Sixteen female and four male patients suffering from very acute and therefore untreated CRPS with a mean duration of 5.5 weeks were included in this study. Two groups of healthy volunteers served as control groups: the first group (n=18) according to the same study protocol as CRPS patients, and the second group (n=10) after warming up one limb. ⋯ The second control group had an increased unilateral skin temperature after warming up (35.0 vs 34.3 degrees C, p<0.006) and demonstrated a significantly increased vasoconstriction on the warmer side (52.0 vs 20.2%, p<0.03) corresponding to findings in patients with acute CRPS. The present study proves that there are signs of decreased sympathetic activity in the affected limb in very acute CRPS. However, no indication was found for increased sensitivity of vascular alpha-receptors in the very acute stages of CRPS, and there was also no indication for a significant direct contribution of the sympathetic nervous system to pain in very acute CRPS.
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The study of the mechanisms of thermal and mechanical hyperalgesia produced in human inflammatory conditions is dependent on a reliable, consistent model. The present investigation shows that the intraplantar administration of zymosan in the rat hindpaw produces a reliable and quantifiable thermal and mechanical hyperalgesia accompanied by oedema that closely mimics the symptoms of inflammation in man. Prior to the intraplantar injection of zymosan, there was no significant difference in withdrawal latencies, mechanical withdrawal thresholds or paw thickness between the left and right hindpaws. ⋯ In addition, at the greatest dose tested (6.25 mg), all rats showed evidence of licking, biting and shaking of the injected hindpaw for up to 30-45 min after injection. These data demonstrate that the intraplantar injection of zymosan is a reliable and quantifiable model of tonic pain characterized by a dose- and time-dependent thermal and mechanical hyperalgesia accompanied by a robust oedema. This model is likely to be a useful, reliable model in which to study further the central and peripheral mechanisms of hyperalgesia.
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Acta Anaesthesiol Scand Suppl · Jan 1997
Randomized Controlled Trial Clinical TrialA new method to evaluate central sensitization to pain following surgery. Effect of ketamine.