INHIBITION OF A CUTANEOUS NOCICEPTIVE REFLEX BY A NOXIOUS VISCERAL STIMULUS IS MEDIATED BY SPINAL CHOLINERGIC AND DESCENDING SEROTONERGIC SYSTEMS IN THE RAT

The present study examined the spinal pathway and receptors that mediate nocigenic inhibition of the tail-flick (TF) reflex produced by conditioning colorectal distension (CRD). Conditioning CRD (80 mmHg; 30 s) inhibited the TF reflex in all rats studied (n = 29). In 19 rats where intensity-dependent effects of CRD were studied, conditioning CRD in 7 rats facilitated the TF reflex at lesser, non-noxious intensities (mean 7.9 +/- 2.1 mmHg) and inhibited the TF reflex at greater, noxious intensities (40-100 mmHg); conditioning CRD at all intensities tested only inhibited the TF reflex in the other 12 rats. Inhibition of the TF reflex produced by 30 s CRD was short-lasting, repeatable and graded with the intensity of CRD. The mean threshold of CRD for inhibition of the TF reflex to cut off (10 s) was 61.4 +/- 3.3 mmHg (n = 29). Intrathecal pretreatment with atropine or methysergide significantly attenuated the inhibitory effect of CRD on the TF reflex; the effects were time- and dose-related. Intrathecal pretreatment with mecamylamine, phentolamine or naloxone was without effect. Intrathecal administration of physostigmine, an acetylcholinesterase inhibitor, significantly reduced the threshold intensity of conditioning CRD necessary to inhibit the TF reflex to cut off (mean 36.0 +/- 4.0 mmHg; n = 5). Bilateral transections of the spinal dorsolateral funiculi (DLF) did not affect the inhibitory effect of CRD in 4/7 rats and attenuated the inhibitory effect of CRD in the other 3 rats. The antagonistic effect of methysergide on CRD-produced inhibition of the TF reflex was abolished following the DLF transections, while scopolamine retained its efficacy in rats with bilateral DLF transections. These findings provide evidence for involvement of spinal cholinergic interneurons as well as a descending serotoninergic pathway traveling in the DLF in CRD-produced inhibition of the TF reflex.