Increased expression of neuronal nitric oxide synthase in dorsal root ganglion neurons after systemic capsaicin administration.

Nitric oxide synthase which is constitutively expressed in some neurons can be induced in other neurons by pathological conditions. For example, sciatic nerve or pelvic nerve transection induced nitric oxide synthase expression in lumbosacral dorsal root ganglion cells. This occurred in small to medium sized dorsal root ganglion neurons suggesting that this change might be limited to, or most prominent in, C-fiber afferents. These afferents are also very sensitive to the neurotoxin, capsaicin, which can deplete neuropeptide stores in C-fibers and in high doses cause degeneration of C-fiber afferent pathways. The present study was undertaken to determine if a chemically induced injury elicited in small diameter afferent neurons by systemic administration of capsaicin can induce a change in nitric oxide synthase expression similar to that elicited by peripheral nerve injury. Following capsaicin pretreatment (three days) a significant increase in the number of nitric oxide synthase-immunoreactive cells was detected in dorsal root ganglia. The increase was most prominent (34-63 fold) in the L5-S1 dorsal root ganglia but also substantial (2-17 fold) in cervical, caudal thoracic and rostral lumbar dorsal root ganglia. These results indicate that the expression of nitric oxide synthase-immunoreactivity in afferent neurons in the dorsal root ganglia is plastic and can be upregulated in response to chemical stimulation and/or injury. It is possible that nitric oxide formed by enhanced expression of nitric oxide synthase may play a role in capsaicin-induced neurotoxicity.