SNS/PN3 and SNS2/NaN sodium channel-like immunoreactivity in human adult and neonate injured sensory nerves.
Two tetrodotoxin-resistant voltage-gated sodium channels, SNS/PN3 and SNS2/NaN, have been described recently in small-diameter sensory neurones of the rat, and play a key role in neuropathic pain. Using region-specific antibodies raised against different peptide sequences of their alpha subunits, we show by Western blot evidence for the presence of these channels in human nerves and sensory ganglia. The expected fully mature 260 kDa component of SNS/PN3 was noted in all injured nerve tissues obtained from adults; however, for SNS2/NaN, smaller bands were found, most likely arising from protein degradation. There was increased intensity of the SNS/PN3 260 kDa band in nerves proximal to the site of injury, whereas it was decreased distally, suggesting accumulation at sites of injury; all adult patients had a positive Tinel's sign at the site of nerve injury, indicating mechanical hypersensitivity. Injured nerves from human neonates showed similar results for both channels, but neonate neuromas lacked the SNS2/NaN 180 kDa molecular form, which was strongly present in adult neuromas. The distribution of SNS/PN3 and SNS2/NaN sodium channels in injured human nerves indicates that they represent targets for novel analgesics, and could account for some differences in the development of neuropathic pain in infants.
Yiangou
Y
Y
Peripheral Neuropathy Unit, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London, UK.
Birch
R
R
Sangameswaran
L
L
Eglen
R
R
Anand
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D015153:Blotting, Western; D001917:Brachial Plexus / Q000293:injuries / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides / Q000032:analysis* / Q000276:immunology; D015222:Sodium Channels / Q000032:analysis* / Q000276:immunology; D013119:Spinal Cord Injuries / Q000378:metabolism*
D000906:Antibodies; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C568317:SCN10A protein, human; C491886:SCN11A protein, human; C568319:Scn10a protein, rat; D015222:Sodium Channels