While systemic capsaicin in adult rats is known to reduce substance P and somatostatin in primary sensory nerves, it is still unknown if it also affects the production of these peptides at the genetic level. Therefore, we examined the effects of systemically administered capsaicin on the expression of the beta-preprotachykinin, gamma-preprotachykinin, somatostatin, calcitonin gene-related peptide, vasoactive intestinal polypeptide, galanin, neuropeptide Y and neurotrophin receptor family (trkA, trkB, trkC) genes in dorsal root ganglion neurons by in situ hybridization in adult rats. Nerve growth factor is thought to be involved in the regulation of some of these genes. In the control animals, beta-preprotachykinin, gamma-preprotachykinin, calcitonin gene-related peptide, somatostatin, trkA, trkB and trkC messenger RNAs were found in about 30%, 30%, 40%, 10%, 40%, 5% and 20% of the lumbar dorsal root ganglion neurons, respectively. The number of neurons expressing beta/gamma-preprotachykinin and calcitonin gene-related peptide messenger RNAs decreased to about 50% and 70% of the control values, respectively, six days after subcutaneous administration of capsaicin (950 mg/kg). Simultaneously, the number of trkA messenger RNA-expressing neurons also decreased to about 70% of the control level, while the number of neurons expressing trkB and trkC messenger RNAs was unaffected. On the other hand, vasoactive intestinal polypeptide and galanin messenger RNAs, but not neuropeptide Y messenger RNA, began to be expressed in about 10% of dorsal root ganglion neurons after administration of capsaicin, although their messenger RNAs were not detected in the controls. However, the expression of somatostatin messenger RNA was unaffected by the systemic administration of capsaicin. The somatostatin messenger RNA was not co-expressed with vasoactive intestinal polypeptide and galanin messenger RNAs in the sensory neurons of rats given capsaicin. Electron microscopic analysis revealed a few degenerating unmyelinated afferents in sural nerves of the treated rats. The number of small-sized dorsal root ganglion cells labeled with Fluoro-Gold, a retrograde-tracing dye which was injected into the sural nerve of the treated rats, decreased to half of the control number. Our results suggest that systemic administration of capsaicin in adult rats depresses the expression of beta/gamma-preprotachykinin, calcitonin gene-related peptide and trkA messenger RNAs, and induces expression of vasoactive intestinal polypeptide and galanin messenger RNAs in sensory neurons, which may be due to the capsaicin-induced degeneration of a subpopulation of sensory afferents. We also demonstrated that the regulation of somatostatin gene expression in mature sensory neurons is not affected by systemic capsaicin.