Activation in, and adjacent to, the lateral area of the anterior hypothalamus can evoke antinociception that is associated with either increases or decreases in arterial blood pressure. The aim of this study was to determine whether such descending controls may be triggered by activity in cutaneous C-nociceptors and mediated after recruitment of neurones, in particular functional sub-divisions of the periaqueductal grey (PAG).

In twelve pentobarbitone-anaesthetised rats (Sagatal, 60 mg kg^-1 I.P.), glass pipettes were positioned in the ventrolateral (VL-) or dorsolateral/lateral (DL/L) PAG at sites at which injection of DL-homocysteic acid (50 nl, 0.05 M) evoked depressor or pressor responses, respectively. The retrograde tracer cholera toxin B (CTb; 100-200 nl) was then injected at the same sites and the animals allowed to recover. One week later, the animals were re-anaesthetised (Sagatal 60 mg kg^-1 I.P.) and ‘slow’ (2.5 °C s^-1) ramps (30-55 °C) of contact heat applied (six times in each animal) to the dorsal surface of the left hindpaw to preferentially activate C-nociceptors (Yeomans & Proudfit, 1996). Two hours later, to allow time for expression of Fos protein, the animals were killed humanely with an overdose of anaesthetic and perfused with 4 % paraformaldehyde in 0.1 M phosphate buffer. 50 µm sections of the PAG were processed immunocytochemically to visualise injection sites and 40 µm sections of the hypothalamus were processed to visualise neurones labelled retrogradely with CTb and those in which Fos protein was evoked by the heat stimulus. Fos-positive neurones were found bilaterally throughout the region under study with greatest numbers in the lateral areas of the anterior hypothalamus and the suprachiasmatic nucleus (LAAH and SCN; 48.2 ± 6.5 and 55.8 ± 12.3, respectively), the supraoptic nuclei (SON; 53.0 ± 13.2) and the paraventricular nucleus (PVN; 35.8 ± 9.3; all values are means ± S.E.M. of counts made contralateral to the stimulated hindpaw). Data from six animals revealed that 21 % of Fos-positive neurones in LAAH were double-labelled with CTb injected into the ipsilateral VL-PAG. Despite high numbers of Fos-positive neurones, 0 % of neurones in SCN and SON, and less than 1 % in PVN were retrogradely labelled from VL-PAG. In contrast, only 10 % of neurones in LAAH and 3 % of neurones in PVN were double-labelled from the ipsilateral DL/L-PAG (n = 6).

These data support the view that neurones in LAAH may be activated by peripheral C-nociceptors and exert their effects on spinal processing after engaging descending systems that originate in the VL-PAG predominantly.This work was supported by the Wellcome Trust. D.A.A.S. is a BBSRC scholar and S.McM. a University of Bristol scholar.

Yeomans, D.C. & Proudfit, H.K. (1996). Pain 68, 141-150.