Articles: hyperalgesia.
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Pain sensitivity was assessed in 11 patients (age 60 +/- 10 years) with 'primary' restless leg syndrome (RLS) (disease duration 18 +/- 15 years) and 11 age- and gender-matched healthy control subjects. Stimulus-response functions for pricking pain were obtained with seven calibrated punctate mechanical stimulators activating Adelta-high threshold mechano-nociceptors. Stimuli at the foot were significantly more painful than at the hand in both patients and healthy control subjects both in the morning and evening. ⋯ Our study shows that patients with RLS exhibit a profound static mechanical hyperalgesia to pin-prick stimuli, but no dynamic mechanical hyperalgesia (allodynia). This type of hyperalgesia is probably mediated by central sensitization to Adelta-fibre high-threshold mechanoreceptor input, a hallmark sign of the hyperalgesia type of neuropathic pain. The reduction of hyperalgesia in RLS patients by long-term dopaminergic treatment suggests that the pathophysiology of RLS includes disturbed supraspinal pain modulation involving the basal ganglia and/or descending dopaminergic pathways.
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Pharmacol. Biochem. Behav. · Apr 2004
Comparative StudyNefopam potentiates morphine antinociception in allodynia and hyperalgesia in the rat.
The objective of this study was to resolve discrepancies regarding the possible antinociceptive synergy between morphine and nefopam in animal models of pain. Firstly, we have examined the antinociceptive activity of nefopam, a nonopioid antinociceptive compound that inhibits monoamine reuptake, in pain models of allodynia and hyperalgesia induced by carrageenan injection, or skin and muscle incision of the rat hind paw. Single subcutaneous administration of nefopam at 30 mg/kg blocked carrageenan- and incision-induced thermal hyperalgesia, and weakly but significantly diminished carrageenan-induced tactile allodynia. ⋯ Combination of a nonanalgesic dose of nefopam (10 mg/kg) with a nonanalgesic dose of morphine (0.3 or 1.0 mg/kg) completely inhibited carrageenan- or incision-induced thermal hyperalgesia, respectively. In carrageenan-induced tactile allodynia, coadministration of weak analgesic doses of nefopam (10 and 30 mg/kg) with a nonanalgesic dose (1 mg/kg) or moderately analgesic dose (3 mg/kg) of morphine significantly reduced or reversed allodynia, respectively. In conclusion, coadministration of nefopam with morphine enhances the analgesic potency of morphine, indicating a morphine sparing effect of nefopam.
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Inhibitors of the isozyme cyclooxygenase-2 (COX-2) represent an important advance in pain management, although where and when these inhibitors can exert their antihyperalgesic actions are not completely understood. Here we show that unlike many peripheral tissues in which COX-2 is only expressed in physiologically significant levels after tissue injury, in the normal rat lumbar spinal cord, the majority of neurons and radial glia constitutively express high levels of COX-2 protein. ⋯ The present data demonstrate that constitutively expressed spinal COX-2 plays an important role in the initial hyperalgesia that follows peripheral tissue injury. These results suggest that blocking constitutive spinal COX-2 before tissue injury may reduce the initial peripheral and central sensitization that occurs after tissue injury.
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Brain research bulletin · Mar 2004
Comparative StudyAttenuation of mechanical but not thermal hyperalgesia by electroacupuncture with the involvement of opioids in rat model of chronic inflammatory pain.
Opioid peptides have been proven effective in reducing the sign of hyperalgesia associated with inflammation. Electroacupuncture (EA) produces antinociception via release of endogenous opioid peptides in normal rats. ⋯ The results are the following: (1) single session of 100Hz EA (0.5-1.0-1.5 mA, 10 min for each intensity) at both Zusanli (ST 36) and Sanyinjiao acupoints (SP 6) significantly increased mechanical withdrawal threshold determined by von Frey filaments but not with thermal withdrawal latency that is determined by hot plate (52 +/- 0.2 degrees C); (2) 100 Hz EA applied twice a week for 4 weeks and showed a significant decrease in the mechanical hyperalgesia at the third and fourth week, with no effect on thermal hyperalgesia; (3) naloxone (20 mg kg(-1)) had the ability to reverse the inhibition of the mechanical hyperalgesia produced by a single session of EA. In conclusion, the present results indicate that a single or repetitive EA could reduce mechanical hyperalgesia, but not thermal hyperalgesia, in CFA-inflammatory pain rats, and the opioid system might be involved in these effects.
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Randomized Controlled Trial Clinical Trial
The cyclooxygenase isozyme inhibitors parecoxib and paracetamol reduce central hyperalgesia in humans.
Non-steroidal antiinflammatory drugs (NSAIDs) are known to induce analgesia mainly via inhibition of cyclooxygenase (COX). Although the inhibition of COX in the periphery is commonly accepted as the primary mechanism, experimental and clinical data suggest a potential role for spinal COX-inhibition to produce antinociception and reduce hypersensitivity. We used an experimental model of electrically evoked pain and hyperalgesia in human skin to determine the time course of central analgesic and antihyperalgesic effects of intravenous parecoxib and paracetamol (acetaminophen). ⋯ In conclusion, our results provide clear experimental evidence for the existence of central antihyperalgesia induced by intravenous infusion of two COX inhibitors, parecoxib and paracetamol. Since the electrical current directly stimulated the axons, peripheral effects of the COX inhibitors on nociceptive nerve endings cannot account for the reduction of hyperalgesia. Thus, besides its well-known effects on inflamed peripheral tissues, inhibition of central COX provides an important mechanism of NSAID-mediated antihyperalgesia in humans.