Noxious-evoked c-fos expression in brainstem neurons immunoreactive for GABAB, mu-opioid and NK-1 receptors.

Modulation of nociceptive transmission at the brainstem involves several neurochemical systems. The precise location and specific characteristics of nociceptive neurons activated in each system was never reported. In this study, the presence of GABA(B), mu-opioid, and neurokinin-1 (NK-1) receptors in brainstem nociceptive neurons was investigated by double-immunocytochemical detection of each receptor and noxious-evoked induction of the c-fos proto-oncogene. Noxious cutaneous mechanical stimulation significantly increased the proportions of neurons double-labelled for Fos and GABA(B) receptors in several brainstem regions, namely, the reticular formation of the caudal ventrolateral medulla (VLMlat and VLMrf), lateral reticular nucleus, spinal trigeminal nucleus, pars caudalis (Sp5C), nucleus of the solitary tract, dorsal reticular nucleus, ventral reticular nucleus, raphe obscurus nucleus and dorsal parabrachial nucleus (DPB). For mu-opioid receptors, the proportions of double-labelled neurons in noxious-stimulated animals were higher than in controls only in the VLMlat, VLMrf, Sp5C, DPB and A5 noradrenergic cell group. As for the NK-1 receptor, no significant differences were found between control and stimulated animals. According to these results, neurons expressing GABA(B), mu-opioid and NK-1 receptors at several pain control centres of the brainstem are differentially involved in processing nociceptive mechanical input. The data provide the definition of new supraspinal targets for selective modulation of nociceptive neurons in order to define better strategies of pain control.