Articles: hyperalgesia.
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To investigate the mechanism of vincristine-induced pain in humans undergoing chemotherapy we have established a model of vincristine-induced hyperalgesia in rat. Vincristine (100 micrograms/kg) was administered daily over a period of two weeks. An acute dose-dependent decrease in mechanical nociceptive threshold and an increased response to non-noxious mechanical stimuli ("hyperalgesia") occurred after the second day of administration. ⋯ At a dose that produced hyperalgesia (100 micrograms/kg), vincristine did not cause a significant motor deficit. Peripheral administration of a mu-opioid agonist did not reduce vincristine-induced acute hyperalgesia. Hyperalgesia induced by vincristine in the rat provides a good model for the experimental study of painful peripheral neuropathies in human patients receiving vincristine as a chemotherapeutic agent.
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Clinical Trial Controlled Clinical Trial
The effect of Ketamine on stimulation of primary and secondary hyperalgesic areas induced by capsaicin--a double-blind, placebo-controlled, human experimental study.
The non-competitive NMDA-antagonist, Ketamine, was infused (i.v.) in healthy volunteers to study the effect on central excitability with the presence of cutaneous hyperalgesia. Hyperalgesia was established experimentally on the dorsum of the foot by topical application of capsaicin (1%). Different thermal and mechanical conditioning stimuli were applied to the primary and secondary hyperalgesic areas to modulate the central nociceptive excitability monitored by the nociceptive reflex. ⋯ Ketamine caused an increase in the summation threshold compared to the placebo treatment. In conclusion, these results demonstrate that (1) summation of activity in non-nociceptive and nociceptive afferents occurs under hyperalgesic conditions and, (2) this summation can be inhibited by NMDA-antagonists. Therefore, the study shows an apparent involvement of NMDA-receptors in some of the central mechanisms underlying secondary hyperalgesia.
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1. Evidence of an adrenergic component of cutaneous hyperalgesia has recently been obtained in animal models of painful peripheral neuropathy. These findings have prompted speculation that an increased density or sensitivity of peripheral alpha-adrenoceptors contributes to sensory abnormalities and chronic neuropathic pain in conditions such as reflex sympathetic dystrophy. ⋯ The mean density of alpha 1-adrenoceptors in the pain-free skin of patients (26.9 grains/1000 microns2) fell midway between receptor density in hyperalgesic skin and in the skin of normal individuals, and did not differ significantly from either. 5. Our findings indicate that alpha 1-adrenoceptors are present in the epidermis, and suggest that their numbers may be increased in the hyperalgesic skin of patients with reflex sympathetic dystrophy. Further studies need to identify the dermal and epidermal cell types that express high densities of alpha 1-adrenoceptors, and to investigate their normal function and role in neuropathic pain.
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Neuroscience letters · Jun 1996
Sciatic nerve section induces mechanical hyperalgesia in skin adjacent to the deafferented region in rats: lack of correlation with autotomy behavior.
We have studied the development of cutaneous hypersensitivity in the innervation area of the saphenous nerve and autotomy behavior in rats after unilateral sciatic nerve section. Hypersensitivity was assessed by stimulating the saphenous area with mechanical (von Frey hairs and analgesimeter), cold (immersion) or heat (immersion or radiant heat) stimuli 10 days after sciatic nerve section. We did not observe any hypersensitivity to thermal stimulation or weak mechanical stimulation produced by von Frey hairs. ⋯ Eleven of 17 rats had started autotomy at this time, but there was no correlation between the presence of autotomy and mechanical hyperalgesia. It is concluded that in our experimental setting, only mechanical hyperalgesia was present 10 days after axotomy. Moreover, autotomy behavior and adjacent hyperalgesia may be triggered by different mechanisms.
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Randomized Controlled Trial Clinical Trial Controlled Clinical Trial
Effect of systemic N-methyl-D-aspartate receptor antagonist (ketamine) on primary and secondary hyperalgesia in humans.
Ketamine reduces nociception by binding noncompetitively to the N-methyl-D-aspartate (NMDA) receptor, activation of which increases spinal hypersensitivity. We studied 19 healthy, unmedicated male volunteers, aged 20-31 yr. Burn injuries were produced on the medial surface of the dominant calf with a 25 x 50 mm rectangular thermode. ⋯ In contrast, ketamine did not alter phasic heat pain perception (perception of transient, painful, thermal stimuli) in undamaged skin. The analgesic effects of ketamine in the burn injury model are in agreement with results from experimental studies, and can be distinguished from those of local anaesthetics and opioids. Side effects caused by continuous infusion of ketamine 0.15 and 0.30 mg kg-1 h-1 were frequent but clinically acceptable.