Using in situ hybridization, we studied nitric oxide (NO) synthase (EC 1.14.23.-) mRNA in lumbar dorsal root ganglia after peripheral transection of the sciatic nerve in rats. The effect of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester on the nociceptive flexor reflex was also studied in axotomized rats. Nerve section induced a dramatic increase in number of NO synthase mRNA-positive cells in the ipsilateral dorsal root ganglia. In some of these cells the peptides galanin and/or vasoactive intestinal polypeptide and/or neuropeptide Y were also strongly up-regulated. Intravenous administration of nitro-L-arginine methyl ester blocked spinal hyperexcitability at much lower dosages in axotomized than in normal animals. The results suggest involvement of NO in the function of lumbar sensory neurons, especially after axotomy, perhaps preferentially at peripheral sites.