Spinal alpha3beta2* nicotinic acetylcholine receptors tonically inhibit the transmission of nociceptive mechanical stimuli.

The presence of non-alpha4beta2, non-alpha7 nicotinic acetylcholine receptors (nAChR) in the rat spinal cord has been suggested previously, but the identity of these nAChRs had not been shown. Intrathecal administration of the alpha3beta2*/alpha6beta2* selective alpha-conotoxin MII (alpha-CTX MII) dose- and time-dependently reduced paw withdrawal thresholds to mechanical pressure in normal rats. The pronociceptive effect of alpha-CTX MII was partially blocked by NMDA receptor antagonism and lost completely following ablation of C-fibers.

Peripheral nerve injury alters spinal nicotinic acetylcholine receptor pharmacology.

Nicotinic acetylcholine receptors are widely expressed in the rat spinal cord and modulate innocuous and nociceptive transmission. The present studies were designed to investigate the plasticity of spinal nicotinic acetylcholine receptors modulating mechanosensitive information following spinal nerve ligation. A tonic inhibitory cholinergic tone mediated by dihydro-beta-erythroidine- (DHbetaE) and methyllycaconitine- (MLA) sensitive nicotinic acetylcholine receptors was identified in the normal rat spinal cord and cholinergic tone at both populations of nicotinic acetylcholine receptors was lost ipsilateral to spinal nerve ligation.

Increased spinal dynorphin contributes to chronic nicotine-induced mechanical hypersensitivity in the rat.

Chronic nicotine administration has been shown previously to produce mechanical hypersensitivity in the rat although the mechanism of this effect is unknown. Rats treated with chronic systemic nicotine 3.6 or 8.

Impact of chronic nicotine on sciatic nerve injury in the rat.

Chronic nicotine exposure and the immune response to peripheral nerve injury has not been investigated thoroughly. Rats were exposed to chronic nicotine or saline followed by chronic constriction injury (CCI) of the sciatic nerve. Mechanical sensitivity was measured at various time points and the immune response was investigated at 21 days post-CCI.

Molecular mechanism for analgesia involving specific antagonism of alpha9alpha10 nicotinic acetylcholine receptors.

alpha9alpha10 nicotinic acetylcholine receptors (nAChRs) have been identified in a variety of tissues including lymphocytes and dorsal root ganglia; except in the case of the auditory system, the function of alpha9alpha10 nAChRs is not known. Here we show that selective block (rather than stimulation) of alpha9alpha10 nAChRs is analgesic in an animal model of nerve injury pain. In addition, blockade of this nAChR subtype reduces the number of choline acetyltransferase-positive cells, macrophages, and lymphocytes at the site of injury.