REGULATION OF EXPRESSION OF THE SENSORY NEURON-SPECIFIC SODIUM-CHANNEL SNS IN INFLAMMATORY AND NEUROPATHIC PAIN

Increased voltage-gated sodium channel activity may contribute to the hyperexcitability of sensory neurons in inflammatory and neuropathic p ain states, Mie examined the levels of the transcript encoding the tet rodotoxin-resistant sodium channel SNS in dorsal root ganglion neurons in a range of inflammatory and neuropathic pain models in the rat. Lo cal Freund's adjuvant, or systemic nerve growth factor-induced inflamm ation did not substantially alter the total levels of SNS mRNA. When N GF-treated adult rat DRG neurons in vitro were compared with NGF-deple ted control neurons, SNS total mRNA levels and the levels of membrane- associated immunoreactive SNS showed a small increase (17 and 25%, res pectively), while CGRP levels increased fourfold. SNS expression is th us little dependent on NGF even though SNS transcript levels dropped b y more than 60% 7-14 days after axotomy. In the streptozotocin diabeti c rat SNS levels fell 25%, while in several manipulations of the L5/6 tight nerve ligation rat neuropathic pain model, SNS levels fell 40-80 % in rat strains that are either susceptible or relatively resistant t o the development of allodynia. Increased expression of SNS mRNA is th us unlikely to underlie sensory neuron hyperexcitability associated wi th inflammation, while lowered SNS transcript levels are associated wi th peripheral nerve damage.