Changes in expression of voltage-dependent ion channel subunits in dorsal root ganglia of rats with radicular injury and pain

Abstract

Study design: Changes in expression of voltage-dependent ion channel subunits were examined in the radicular pain state. Furthermore, antinociceptive effects of gabapentin on radicular pain were compared with effects on peripheral neuropathic pain.

Objectives: To clarify molecular substrates involved in the development of radicular pain, and to investigate the responsiveness of radicular pain to gabapentin.

Summary of background data: Peripheral nerve injuries are known to induce dynamic changes of voltage-dependent Na+ and Ca2+ channel subunits expression in dorsal root ganglion neurons. However, the expression profiles of Na+ and Ca2+ channel subunits in the radicular pain state have not been examined.

Methods: Two radicular pain models and one peripheral neuropathic pain model were prepared. By using semiquantitative reverse transcriptase-polymerase chain reaction, the expression levels of several Na+ and Ca2+ channel subunits in the dorsal root ganglions of these pain model rats were investigated. The antinociceptive effects of gabapentin were examined in a behavioral study using the aforementioned pain models.

Results: All three neuropathic pain operations induced comparable mechanical allodynia and thermal hyperalgesia. The upregulation of the Na(v)1.3 Na+ channel and Ca(v)alpha2delta Ca2+ channel subunits was observed only in the peripheral nerve injury model. A downregulation of the Na(v)1.9 channel was observed in all three pain model rats. A lower dose of gabapentin was significantly more effective in alleviating the mechanical allodynia of rats with radicular pain.

Conclusions: The reduction of Na(v)1.9 found in all three models may link to the neuropathic pain state, including radicular pain. The lower sensitivity to gabapentin in rats with peripheral neuropathic pain might be partly explained by the marked upregulation of Ca(v)alpha2delta in the dorsal root ganglions, suggesting that gabapentin may be more effective in radicular pain treatment.