Articles: hyperalgesia.
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Withdrawal reflex responses to graded von Frey filaments applied to the plantar surface of the paw were measured before and after bone hole damage in rats with either a dorsal column (DC) lesion or a sham DC lesion. Two methods were employed to produce models of osteotomy; a small hole was drilled through either the (1) tibia or (2) calcaneus (Houghton, A. K., Hewitt, E. and Westlund, K. ⋯ Nocifensive behavior, characterized by a lifting and guarding of the damaged limb, was also observed in animals with a hole through the calcaneus. In contrast, we found that interrupting the dorsal column pathway with a small mid-line lesion (1 week prior to the osteotomy) prevented the development of both the primary and secondary mechanical hyperalgesia and allodynia but not the guarding of the damaged limb. This study provides evidence that axons in the medial part of the dorsal column are involved in the development of mechanical hyperalgesia and allodynia after bone hole injury.
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J. Pharmacol. Exp. Ther. · Jul 1999
Potent antihyperalgesic activity without tolerance produced by glycine site antagonist of N-methyl-D-aspartate receptor GV196771A.
Central sensitization is a condition of enhanced excitability of spinal cord neurons that contributes to the exaggerated pain sensation associated with chronic tissue or nerve injury. N-methyl-D-aspartate (NMDA) receptors are thought to play a key role in central sensitization. We have tested this hypothesis by characterizing in vitro and in vivo a novel antagonist of the NMDA receptor acting on its glycine site, GV196771A. ⋯ These antihyperalgesic properties were not accompanied by development of tolerance. These observations strengthen the view that NMDA receptors play a key role in the events underlying plastic phenomena, including hyperalgesia. Moreover, antagonists of the NMDA glycine site receptor could represent a new analgesic class, effective in conditions not sensitive to classical opioids.
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1DMe, a neuropeptide FF (NPFF) analogue, has been shown to produce antinociception and to enhance morphine analgesia in rats after intrathecal administration. To determine whether 1DMe could correct hyperalgesia and restore morphine efficacy in mononeuropathic (MN) and diabetic (D) rats we examined the spinal effect of 1DMe in MN and D rats without and after spinal blockade of mu- and delta-opioid receptors with CTOP and naltrindole, respectively. The influence of 1DMe on morphine-induced antinociception was assessed in the two models using isobolographic analysis. ⋯ The combinations of morphine: 1DMe (80.6:19.4% and 99.8:0.2%, in MN and D rats, respectively) followed by isobolographic analysis, showed a superadditive interaction, relative to the antinociceptive effect of single doses, in D rats only. In N rats, the combination of morphine: 1DMe (0.5 mg kg(-1), i.v.: 1 microg rat(-1), i.t., ineffective doses) resulted in a weak short-lasting antinociceptive effect. These results show a different efficacy of 1DMe according to the pain model used, suggesting that the pro-opioid effects of the NPFF in neuropathic pain are only weak, which should contribute to hyperalgesia and to the impaired efficacy of morphine.
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Central sensitization, the hyperexcitability of spinal processing that often accompanies peripheral injury, is a major component of many persistent pain states. Here we report that the neurotrophin, brain-derived neurotrophic factor (BDNF), is a modulator of excitability within the spinal cord and contributes to the mechanism of central sensitization. BDNF, localized in primary sensory neuron cell bodies and central terminals, potentiates nociceptive spinal reflex responses in an in vitro spinal cord preparation and induces c-fos expression in dorsal horn neurons. ⋯ Thus behavioral nociceptive responses induced by intraplantar formalin and by intraplantar carageenan are significantly attenuated by trkB-IgG. Hence BDNF is appropriately localized and regulated in inflammatory states and is sufficient and necessary for the expression of central sensitization in the spinal cord. We propose that BDNF may function as a modulator of central sensitization in pathological states, and our results suggest that pharmacological antagonism of BDNF may prove an effective and novel analgesic strategy for the treatment of persistent inflammatory pain states.
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Dose-dependency and time course of hyperalgesia and erythema following UVA (16.8 and 36 J/cm(2)) and UVB (one and three times the minimum erythema threshold) irradiation was investigated in 10 healthy human subjects. Skin patches (1.5 cm in diameter) on the ventral side of the upper leg were irradiated with UVA or UVB light. Hyperaemia (Laser Doppler flowmetry, infrared thermography), thermal hyperalgesia to radiant heat stimuli, and mechanical hyperalgesia to controlled impact stimuli were tested at 1, 6, 12, 24, 48 and 96 h after irradiation. ⋯ It is concluded that UVB- but not UVA-irradiation is a suitable experimental model of subacute thermal and mechanical hyperalgesia. The different time courses of erythema and hyperalgesia indicate that inflammatory mediators responsible for vasodilatation are not identical with those inducing hyperalgesia. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.