Voltage-gated sodium channel expression in rat and human epidermal keratinocytes: Evidence for a role in pain Export

@article{citeulike:3282907, abstract = {Keratinocytes are implicated in sensory transduction and can influence nociception, but whether these contribute to chronic pain is not known. In neurons, voltage-gated sodium channels (Nav) are involved in neuropathic pain and are activated by depolarization. Since keratinocytes can also show changes in membrane potential, we used RT-PCR, in situ hybridization, and immunohistochemistry to investigate the expression of sodium channels in these cells. Nav1.1, Nav1.6, and Nav1.8 were localized within keratinocytes in rat epidermis. In addition, sodium channels contribute to the release of ATP from rat keratinocytes in response to increased [K+]o, implicating sodium channels in keratinocyte ligand release and nociception. To examine whether keratinocytes may contribute to human pain states, we analyzed sodium channel expression in human skin biopsies from subjects with complex regional pain syndrome Type 1 (CRPS) and post-herpetic neuralgia (PHN) using immunohistochemistry. Control skin exhibited immunolabeling for Nav1.5, Nav1.6 and Nav1.7. In contrast, painful skin from CRPS and PHN subjects displayed Nav1.1, Nav1.2, and Nav1.8 immunolabeling, in addition to substantially increased signal for Nav1.5, Nav1.6, Nav1.7. These observations lead us to propose that pathological increases in keratinocyte sodium channel expression may contribute to pain by increasing epidermal ATP release, resulting in excessive activation of P2X receptors on primary sensory axons. Consistent with this hypothesis, animal models of neuropathic pain exhibit increases in subcutaneous ATP release and activity of primary sensory neurons, and peripheral administration of P2X antagonists has been shown to reduce neuropathic pain in humans.}, author = {Zhao, Peng and Barr, Travis P. and Hou, Quanzhi and Dib-Hajj, Sulayman D. and Black, Joel A. and Albrecht, Phillip J. and Petersen, Karin and Eisenberg, Elon and Wymer, James P. and Rice, Frank L. and Waxman, Stephen G.}, citeulike-article-id = {3282907}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.pain.2008.03.016}, citeulike-linkout-1 = {http://www.sciencedirect.com/science/article/B6T0K-4SCTSS7-1/2/4dc1d5eaa802078421699c7f0e73d744}, comment = {JC?}, day = {30}, doi = {10.1016/j.pain.2008.03.016}, journal = {Pain}, keywords = {pain, sodiumchannel}, month = {September}, number = {1}, pages = {90--105}, posted-at = {2008-09-18 01:11:25}, priority = {2}, title = {Voltage-gated sodium channel expression in rat and human epidermal keratinocytes: Evidence for a role in pain}, url = {http://dx.doi.org/10.1016/j.pain.2008.03.016}, volume = {139}, year = {2008} }

TY - JOUR ID - citeulike:3282907 L3 - citeulike-article-id:3282907 N2 - Keratinocytes are implicated in sensory transduction and can influence nociception, but whether these contribute to chronic pain is not known. In neurons, voltage-gated sodium channels (Nav) are involved in neuropathic pain and are activated by depolarization. Since keratinocytes can also show changes in membrane potential, we used RT-PCR, in situ hybridization, and immunohistochemistry to investigate the expression of sodium channels in these cells. Nav1.1, Nav1.6, and Nav1.8 were localized within keratinocytes in rat epidermis. In addition, sodium channels contribute to the release of ATP from rat keratinocytes in response to increased [K+]o, implicating sodium channels in keratinocyte ligand release and nociception. To examine whether keratinocytes may contribute to human pain states, we analyzed sodium channel expression in human skin biopsies from subjects with complex regional pain syndrome Type 1 (CRPS) and post-herpetic neuralgia (PHN) using immunohistochemistry. Control skin exhibited immunolabeling for Nav1.5, Nav1.6 and Nav1.7. In contrast, painful skin from CRPS and PHN subjects displayed Nav1.1, Nav1.2, and Nav1.8 immunolabeling, in addition to substantially increased signal for Nav1.5, Nav1.6, Nav1.7. These observations lead us to propose that pathological increases in keratinocyte sodium channel expression may contribute to pain by increasing epidermal ATP release, resulting in excessive activation of P2X receptors on primary sensory axons. Consistent with this hypothesis, animal models of neuropathic pain exhibit increases in subcutaneous ATP release and activity of primary sensory neurons, and peripheral administration of P2X antagonists has been shown to reduce neuropathic pain in humans. IS - 1 JF - Pain EP - 105 TI - Voltage-gated sodium channel expression in rat and human epidermal keratinocytes: Evidence for a role in pain VL - 139 SP - 90 KW - pain KW - sodiumchannel N1 - JC? AU - Zhao, Peng AU - Barr, Travis AU - Hou, Quanzhi AU - Dib-Hajj, Sulayman AU - Black, Joel AU - Albrecht, Phillip AU - Petersen, Karin AU - Eisenberg, Elon AU - Wymer, James AU - Rice, Frank AU - Waxman, Stephen PY - 2008/09/30/ UR - http://dx.doi.org/10.1016/j.pain.2008.03.016 ER -