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


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


BACKGROUND
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.
Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Masahiro
M
Abe
Takashi
T
Kurihara
Wenhua
W
Han
Kenichi
K
Shinomiya
Tsutomu
T
Tanabe
D000085:Acetates / Q000494:pharmacology; D000588:Amines; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015220:Calcium Channels / Q000235:genetics*; D003509:Cyclohexanecarboxylic Acids; D004195:Disease Models, Animal; D000077206:Gabapentin; D005727:Ganglia, Spinal / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation; D008297:Male; D010146:Pain / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011843:Radiculopathy / Q000150:complications* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D021122:Protein Subunits; D012333:RNA, Messenger; D015222:Sodium Channels; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin