Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain

Previous studies have shown that transection of the sciatic nerve induces dramatic changes in sodium currents of axotomized dorsal root ganglion (DRG) neurons, which are paralleled by significant changes in the levels of transcripts of several sodium channels expressed in these neurons. Sodium currents that are resistant to tetrodotoxin (TTX-R) and the transcripts of two TTX-R sodium channels are significantly attenuated, while a rapidly repriming tetrodotoxin-sensitive (TTX-S) current emerges and the transcripts of alpha-III sodium channel, which produce a TTX-S current when expressed in oocytes, are up-regulated. We report here on changes in sodium currents and sodium channel transcripts in DRG neurons in the chronic constriction injury (CCI) model of neuropathic pain. CCI-induced changes in DRG neurons, 14 days post-surgery, mirror those of axotomy. Transcripts of NaN and SNS, two sensory neuron-specific TTX-R sodium channels, are significantly down-regulated as is the TTX-R sodium current, while transcripts of the TTX-S alpha-III sodium channel and a rapidly repriming TTX-S Na current are up-regulated in small diameter DRG neurons. These changes may provide at least a partial basis for the hyperexcitablity of DRG neurons that contributes to hyperalgesia in this model. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V.