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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A single injection of streptozocin (50 mg/kg, i.p.) led to the development of static and dynamic allodynia in the rat. The two responses were detected, respectively, by application of pressure using von Frey hairs or lightly stroking the hind paw with a cotton bud. Static allodynia was present in the majority of the animals within 10 days following streptozocin. ⋯ In contrast, administration of similar doses of gabapentin into the hind paw failed to block these responses. It is suggested that in this model of neuropathic pain dynamic allodynia is mediated by A beta-fibres and the static type involves small diameter nociceptive fibres. These data suggest that gabapentin and pregabalin possess a superior antiallodynic profile than morphine and amitriptyline, and may represent a novel class of therapeutic agents for the treatment of neuropathic pain.