Non-selective activation of both intrinsic interneurones and output neurones of the periaqueductal grey (PAG) using DL-homocysteic acid (DLH) exerts more pronounced modulation of spinal reflexes evoked by C- compared with Aδ-nociceptors (McMullan & Lumb, 2001). The present study examined the effects of microinjection of the GABAA receptor antagonist bicuculline (BIC) as the first step in investigating the role played by the intrinsic GABAergic system in the selective aspects of descending control originating from the PAG.
Sixteen alphaxalone/alphadolone (Saffan, 14-24 mg kg-1 h-1, I.V.)-anaesthetised male Wistar rats (275-300 g) were instrumented to record arterial blood pressure and rectal temperature. Triple-barrelled micropipettes were inserted stereotaxically into the PAG at sites where injections of DLH (20 nl, 0.05 M) evoked pressor responses. ‘Slow’ (2.5 °C s-1) or ‘fast’ (7.5 °C s-1) ramps (30-55 °C) of contact heat were applied to the dorsal surface of the hindpaw to preferentially activate C- or Aδ-nociceptors, respectively (Yeomans & Proudfit, 1996). Withdrawal to noxious skin heating was monitored by recording EMG activity from the biceps femoris. Threshold temperatures to evoke withdrawal were recorded every 8 min, for 25 min before and for 40 min after injections of BIC (10 nl, 0.4 mM) into the PAG. At the end of the experiments animals were killed with a lethal overdose of barbiturate. Brains were removed and stimulation sites recovered in histological material.
In control periods, the probability of evoking a withdrawal to slow and fast rates of skin heating were 97 % (n = 48 ramps) and 100 % (n = 45 ramps), respectively. The probability of evoking a response to slow ramp stimulation fell to 50 % in the first cycle of stimulation following injection of BIC. In contrast, in the first post-injection cycle, fast heating ramps evoked responses in 93 % of cases. When present, thresholds of withdrawal responses to slow ramps increased significantly from 49.4 ± 1.1 to 51.3 ± 0.8 °C (mean ± S.E.M.; P = 0.02). Paradoxically, thresholds of responses to fast ramps also increased significantly from 52.1 ± 1.0 to 54 ± 1.0 °C (P = 0.02; Wilcoxon matched pairs test) following BIC injection.
Compared with non-selective neuronal activation, the presumed disinhibition of output neurones in the PAG has revealed a more pronounced differential control of C-versus Aδ-evoked spinal reflexes, in that a greater proportion of fast ramps evoked responses following injection of BIC (93 %) compared with the proportion evoked following injection of DLH (64% McMullan & Lumb, 2001). This finding suggests that removal of tonic inhibitory control may provide a more selective means of controlling spinal nociception.S.McM. is a University of Bristol scholar. This work was supported by The Wellcome Trust.
- McMullan, S. & Lumb, B.M. (2001). J. Physiol. 533.P, 72P.
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