Electrophysiological studies have suggested that activity of spinal GABAergic interneurons can be enhanced following intradermal injection of capsaicin (CAP). This activity is proposed to be involved in the generation of dorsal root reflexes (DRRs) that contribute to neurogenic inflammation. We have recently reported that NMDA or non-NMDA antagonists by intrathecal pretreatment attenuate the increased Fos expression in spinal dorsal horn GABAergic neurons after intradermal injection of CAP in rats. Sympathetic efferents have been suggested to modulate inflammatory pain possibly by interactions with primary afferent terminals. In electrophysiological studies by our group, enhancement of the CAP-induced DRRs could be prevented by surgical sympathectomy and blocked by intraarterial pretreatment of the foot with alpha(1)- but not by alpha(2)-adrenoceptor antagonists. In order to determine morphologically if surgical sympathectomy changes the expression of Fos in GABAergic neurons in the lumbosacral spinal cord induced by CAP injection, further experiments were performed using immunofluorescence double-labeling staining at 30 min following CAP or vehicle injection into the glabrous skin of one hind paw of anesthetized rats both in sham-operated and sympathectomized animals. Our results showed that the proportion of Fos-positive GABAergic neuronal profiles was significantly increased following CAP injection (48.8+/-4.76%) compared to vehicle injection (23.8+/-5.1%) in laminae I-V on the ipsilateral side (P<0.05). However, when sympathetic efferents were removed surgically 7-10 days prior to the experiment (n=6), only 32.07+/-9.03% of GABA-immunoreactive neuronal profiles were stained for Fos following CAP injection, a significant reduction in the CAP-evoked Fos-staining of GABAergic neurons after surgical sympathectomy. These findings support our previous electrophysiological studies that GABAergic neurons take part in nociceptive processing within the spinal dorsal horn and suggest that sympathetic efferents may affect nociceptive transduction in the periphery.