Tetrodotoxin-resistant fibres and spinal Fos expression: differences between input from muscle and skin.

Nociceptive information from muscle and skin is differently processed at many levels of the central nervous system. In most articles on this issue, noxious stimuli were used that also excited non-nociceptive receptors. The effects of a pure nociceptive input from muscle or skin on spinal neurones are largely unknown. The aim of the study was to find out whether the Fos-protein expression in dorsal horn neurones induced by an exclusively nociceptive muscle input differs from that of the skin. Fos-proteins are transcription factors that regulate neuronal gene expression and induce neuroplastic effects that are involved in the development of chronic pain. A pure nociceptive input was achieved by tetrodotoxin (TTX) that is known to block all TTX-sensitive afferents and leave the TTX-resistant (TTX-r), presumably nociceptive, afferent fibres intact. We studied the c-Fos and FosB expression in the spinal cord following electrical stimulation of TTX-r afferent fibres in the gastrocnemius-soleus nerve (muscle) and compared it to the sural nerve (skin). In the spinal dorsal horn, the main effect of a TTX-r input from muscle was an increase in FosB (P < 0.05), but not in c-Fos expression (P = 0.51). In contrast, an input from the skin induced both FosB (P < 0.01) and c-Fos expression (P < 0.05). The data indicate that in the spinal, dorsal horn nociceptive input from skin and muscle has different effects on the Fos expression. The only effect of muscle input was an increase in FosB expression while skin input increased both c-Fos and FosB expression.