Pain
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We have shown previously that the development of hyperalgesia and inflammation associated with knee joint arthritis depends on interactions among various receptors in the central and peripheral nervous system in addition to the contribution of blood borne inflammatory mediators. In the present study, the involvement of spinal nicotinic cholinergic receptors in the modulation of inflammatory pain was evaluated using a model of acute arthritis in rats. Epibatidine (EP), a potent agonist for neuronal nicotinic acetylcholine receptors sharing similar structural and functional characteristics with acetylcholine and nicotine, has been used in this study. ⋯ The antinociceptive effect of epibatidine was selectively blocked by the nicotinic receptor antagonist, mecamylamine. Joint circumference and temperature were not selectively altered by mecamylamine suggesting another mechanism involving non-nicotinic receptors in the spinal regulation of joint inflammatory responses. Collectively, these findings provide considerable evidence to suggest an important role for central nicotinic cholinergic receptors in the modulation of persistent pain and neurogenic inflammation mediated by events in the dorsal horn.
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We studied the effect of unilateral ligation of two spinal nerves on behavioral pain responses evoked by various types of cutaneous stimuli in the adult rat. Furthermore, we determined the effect of spinal nerve ligation on morphology of the peripheral nerves. The most consistent behavioral finding (83%) was a marked decrease in monofilament-induced hindlimb withdrawal thresholds (mechanical allodynia) ipsilateral to the spinal nerve ligation. ⋯ However, this mechanical allodynia may differentially dissociate from mechanical and thermal hyperalgesia at various post-operative time points. The marked mechanical allodynia together with a dramatic decrease in the number of myelinated nerve fibers is paradoxical, since the activation of myelinated nerve fibers by monofilaments produced abnormally strong behavioral responses. This paradox may be explained by spinal nerve ligation-induced amplification or disinhibition of tactile signals at central levels.