The roles of T-type calcium channel in the development of neuropathic pain following chronic compression of rat dorsal root ganglia.
This study aimed to elucidate the role of T-type calcium channels in the nociceptive signal transmission at the spinal level. The chronic compression of dorsal root ganglion (CCD) rat model was adopted. Three doses (50, 100 and 200 microg in groups Mib50, Mib100 and Mib200, respectively) of specific T-type Ca2+ channel inhibitors mibefradil (Mib) or normal saline (NS) were intrathecally administered on the 5th day after the CCD model had been established. The paw withdrawal latency from a noxious thermal stimulus and paw withdrawal mechanical threshold of von Frey filament was used to measure the thermal hyperalgesia and tactile allodynia, respectively. Lumbar spinal cords of the rats isolated on the 5th day after the operation were prepared to measure the mRNA expression of T-type (Cav3.1, Cav3.2 and Cav3.3) calcium channel with RT-PCR methods. The results demonstrated that CCD rats produced reliable thermal hyperalgesia and tactile allodynia after surgery. The intrathecal administration of Mib significantly suppressed thermal hyperalgesia and allodynia in CCD rats (p< 0.01), and the inhibitory effect lasted for 2 h. However, only Cav3.2 and Cav3.3 T-type calcium channel mRNA were detected in the lumbar spinal cord of rats, and there were no Cav3.1 calcium channels. Compared with native and sham groups, the Cav3.2 and Cav3.3 calcium channel mRNA expression increased significantly (p < 0.05). These data support the view that spinal T-type calcium (Cav3.2 and Cav3.3 but not Cav3.1) channels may play an important role in the pathogenesis of neuropathic pain.
Wen
Xian-Jie
XJ
Department of Anesthesiology, Affiliated ZhuJiang Hospital of Southern Medical University, Guangzhou, China.
Xu
Shi-Yuan
SY
Chen
Zhi-Xin
ZX
Yang
Cheng-Xiang
CX
Liang
Hua
H
Li
Heng
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000293:injuries*; D005786:Gene Expression Regulation; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy; D008159:Lumbar Vertebrae / Q000378:metabolism; D008297:Male; D020748:Mibefradil / Q000008:administration & dosage / Q000627:therapeutic use; D009408:Nerve Compression Syndromes / Q000378:metabolism / Q000503:physiopathology*; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors; D014110:Touch
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D020033:Protein Isoforms; D012333:RNA, Messenger; D020748:Mibefradil