摘要
Background Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca^2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) contributes to the analgesic effect of gabapentin on a chronic constriction injury (CCI) model. Methods Gabapentin (2%, 100 mg/kg) or saline (0.5 ml/100 g) was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0-4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKⅡ were quantified by reverse-transcriptional polymerase chain reaction and Western blotting. Results The analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKⅡ and phosphorylated CaMKⅡ in CCI rats. Conclusion The analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKⅡ in the spinal cord.
Background Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca^2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) contributes to the analgesic effect of gabapentin on a chronic constriction injury (CCI) model. Methods Gabapentin (2%, 100 mg/kg) or saline (0.5 ml/100 g) was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0-4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKⅡ were quantified by reverse-transcriptional polymerase chain reaction and Western blotting. Results The analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKⅡ and phosphorylated CaMKⅡ in CCI rats. Conclusion The analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKⅡ in the spinal cord.
基金
This research is supported by a grant from the National Natural Science Foundation of China (No. 30672029).