Neurones in the ventrolateral periaqueductal grey (VL-PAG) are believed to co-ordinate changes in sensory, autonomic and somatomotor parameters as part of passive coping strategies in response to inescapable pain (see Lumb, 2002). As part of on-going studies into the triggers of passive coping, the aim of the present study was to localise C-nociceptor-activated spinal cord neurones that project to the VL-PAG.

Experiments were a two-stage process. First, in five pentobarbitone-anaesthetised (Sagatal 60 mg kg^-1, I.P.) adult rats instrumented to record blood pressure, cholera toxin B (CTb; 150 nl) was injected at sites in the right VL-PAG at which previous injection of DL-homocysteic acid (50 nl, 0.05 M) evoked depressor responses. Animals were allowed to recover for 5 days to allow retrograde transport of CTb and then re-anaesthetised as before. In the second stage, ‘slow’ (2.5 °C s^-1) ramps (30Ð55 °C) of contact heat were 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 given an overdose of anaesthetic and perfused with 4 % paraformaldehyde. Sections (50 mm) of the PAG were processed immunocytochemically to visualise injection sites and 40 mm sections of the spinal cord were processed to visualise neurones labelled retrogradely and those in which Fos protein was evoked by the heat stimulus.

Fos-positive neurones were found throughout the dorsal horn and in the lateral spinal nucleus (LSN), with by far the largest numbers (724.2 ± 169.2 (mean ± S.E.M.); 76.6 % of total Fos-positive neurones) found in lamina I and 15.3 % in lamina II. Double-labelled neurones, i.e. those activated by C-nociceptors that projected to the VL-PAG were localised to two regions: lamina I in which 14.8 % of Fos-positive neurones were double labelled and LSN, in which, despite low numbers of Fos-positive neurones (16.2 ± 3.8), 41 % were double labelled. No double-labelled neurones were found in lamina II.

These data demonstrate that C-nociceptor input to the VL-PAG is relayed predominantly in lamina I and the LSN of the spinal dorsal horn. As such, these may represent critical pathways for triggering passive coping strategies in response to C-fibre-mediated pain.

This work was supported by The Wellcome Trust. D.A.A.S. is a BBSRC Scholar. We thank Simon Lishman, Annette Goodall and Dave Gee for technical assistance

All procedures accord with current UK legislation.