The pattern of expression of the voltage-gated sodium channels Na(v)1.8 and Na(v)1.9 does not change in uninjured primary sensory neurons in experimental neuropathic pain models.
A spared nerve injury of the sciatic nerve (SNI) or a segmental lesion of the L5 and L6 spinal nerves (SNL) lead to behavioral signs of neuropathic pain in the territory innervated by adjacent uninjured nerve fibers, while a chronic constriction injury (CCI) results in pain sensitivity in the affected area. While alterations in voltage-gated sodium channels (VGSCs) have been shown to contribute to the generation of ectopic activity in the injured neurons, little is known about changes in VGSCs in the neighboring intact dorsal root ganglion (DRG) neurons, even though these cells begin to fire spontaneously. We have now investigated changes in the expression of the TTX-resistant VGSCs, Nav1.8 (SNS/PN3) and Nav1.9 (SNS2/NaN) by immunohistochemistry in rat models of neuropathic pain both with an intermingling of intact and degenerated axons in the nerve stump (SNL and CCI) and with a co-mingling in the same DRG of neurons with injured and uninjured axons (sciatic axotomy and SNI). The expression of Nav1.8 and Nav1.9 protein was abolished in all injured DRG neurons, in all models. In intact DRGs and in neighboring non-injured neurons, the expression and the distribution among the A- and C-fiber neuronal populations of Nav1.8 and Nav1.9 was, however, unchanged. While it is unlikely, therefore, that a change in the expression of TTX-resistant VGSCs in non-injured neurons contributes to neuropathic pain, it is essential that molecular alterations in both injured and non-injured neurons in neuropathic pain models are investigated.
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Department of Anesthesiology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland Surgical Research Division and Gene Therapy Center, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA Department of Gene Expression and Protein Biochemistry, Discovery Research, GlaxoSmithKline, Stevenage SG1 2NY, UK.
Ji
Ru-Rong
RR
Abdi
Salahadin
S
Tate
Simon
S
Woolf
Clifford J
CJ
D000818:Animals; D019771:Axotomy; D048429:Cell Size; D005727:Ganglia, Spinal / Q000166:cytology*; D008297:Male; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism; D012585:Sciatica / Q000378:metabolism*; D015222:Sodium Channels / Q000032:analysis / Q000096:biosynthesis*; D013126:Spinal Nerve Roots / Q000293:injuries / Q000378:metabolism; D013497:Sural Nerve / Q000378:metabolism
D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C568319:Scn10a protein, rat; C113705:Scn11a protein, rat; D015222:Sodium Channels