Immunolocalization of SNS/PN3 and NaN/SNS2 sodium channels in human pain states

The tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel SNS/PN3 and the newly discovered NaN/SNS2 are expressed in sensory neurones, particula rly in nociceptors. Using specific antibodies, we have studied, for the fir st time in humans, the presence of SNS/PN3 and NaN/SNS2 in peripheral nerve s, including tissues from patients with chronic neurogenic pain. In brachia l plexus injury patients, there was an acute decrease of SNS/PN3- and NaN/S NS2-like immunoreactivity in sensory cell bodies of cervical dorsal root ga nglia (DRG) whose central axons had been avulsed from spinal cord, with gra dual return of the immunoreactivity to control levels over months. In contr ast, there was increased intensity of immunoreactivity to both channels in some peripheral nerve fibers just proximal to the site of injury in brachia l plexus trunks, and in neuromas. These findings suggest that the expressio n of these sodium channels in neuronal cell bodies is reduced after spinal cord root avulsion injury in man, but that pre-synthesized channel proteins may undergo translocation with accumulation at sites of nerve injury, as i n animal models of peripheral axotomy. The latter may contribute to positiv e symptoms, as our patients all showed a positive Tinel's sign. Nerve termi nals in distal limb neuromas and skin from patients with chronic local hype ralgesia and allodynia all showed marked increases of SNS/PN3-immunoreactiv e fibers, but little or no NaN/SNS2-immunoreactivity, suggesting that the f ormer may be related to the persistent hypersensitive state. Axonal immunor eactivity to both channels was similar to control nerves in sural nerve bio psies in a selection of neuropathies, irrespective of nerve inflammation, d emyelination or spontaneous pain, including a patient with congenital insen sitivity to pain. Our studies suggest that the best target for SNS/PN3 bloc king agents is likely to be chronic local hypersensitivity. (C) 2000 Intern ational Association for the Study of Pain. Published by Elsevier Science B. V. All rights reserved.