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. The effect of spinal nerve ligation on alpha-CTX MII-induced mechanical hypersensitivity was also assessed. Sensitivity was lost in the hind paw ipsilateral to spinal nerve ligation, but maintained in the contralateral hind paw at control levels. Radioligand binding in spinal cord membranes revealed high and low affinity alpha-CTX MII binding sites. Spinal nerve ligation did not significantly alter alpha-CTX MII binding ipsilateral to ligation. Finally, no evidence for the presence of alpha6-containing nAChRs was identified. The results of these studies show the presence of 2 populations of alpha-CTX MII-sensitive nAChRs containing the alpha3 and beta2, but not the alpha6, subunits in the rat spinal cord that function to inhibit the transmission of nociceptive mechanical stimuli via inhibiting the release of glutamate from C-fibers. Spinal nerve ligation produces a unilateral loss of alpha-CTX MII-induced mechanical hypersensitivity without altering alpha-CTX MII binding sites. Our data support a peripheral injury-induced loss of a cholinergic inhibitory tone at spinal alpha3beta2* nAChRs, without the loss of the receptors themselves, which may contribute to mechanical hypersensitivity following spinal nerve ligation.