Sodium Channel Redistribution and Neuropathic Pain Redistribution of NaV1.8 in Uninjured Axons Enables Neuropathic Pain

Pain resulting from chronic nerve injury or damage (so-called neuropathic pain) is a common and debilitating condition. Many studies indicate that tetrodotoxinresistant (TTX-R) sodium channels are highly expressed in nociceptors, the sensory neurons that mediate pain. It has also been suggested that a reduction in TTX-R expression or function reduces pain. Similarly, because axonal injury causes hyperexcitability, it has been proposed that increases in sodium channel expression in injured neurons account for neuropathic pain. However, Gold et al. present evidence that sodium channel redistribution contributes to neuropathic pain. They ligated lumbar nerves 5 and 6, a standard rat model of neuropathic pain. Tactile sensitivity increased, and withdrawal latencies to thermal stimuli decreased 7 d after injury. The authors compared the characteristics of neurons in the L4 dorsal root ganglion (DRG) (uninjured) with the L5 DRG (injured). They found that the NaV1.8, a TTX-resistant sodium channel that is exclusively expressed in primary sensory neurons, was downregulated in injured DRG cell bodies, but NaV1.8 immunoreactivity and TTX-R sodium channels were increased along the sciatic nerve, primarily because of redistribution of TTX-R sodium channels to axons of uninjured nerves. Thus both changes in expression and redistribution of sodium channels may underlie neuropathic pain. ΠDevelopment/Plasticity/Repair