Effect of Gabapentin on c-Fos Expression in the CNS after Paw Surgery in Rats
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- Kazi, J.A. & Gee, C.F. J Mol Neurosci (2007) 32: 228. doi:10.1007/s12031-007-0048-x
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Gabapentin (neurontin), a GABA analogue anticonvulsant has proven to be effective in anti-nociceptive activity as well as for the treatment of anxiety. Gabapentin (GBP) is well tolerated and shows very favorable side effects profile: The exact molecular mechanism of action of GBP to block postoperative pain and stress is not known. Therefore, to identify the functional neuroanatomical target sites of GBP in post-surgery as well as its effect on postsurgical process, we examined the effects of GBP on c-Fos expression in the supraspinal part of the central nervous system in rats. Using a well-validated rat model of surgical pain, we studied the neuroanatomical functional target sites of gabapentin after paw surgery. The effect of GBP was examined by means of c-Fos immunohistochemistry. A single intraperitoneal injection (i.p.) of GBP (150 mg/kg) or saline (control) was administered 20 min before surgical incision in the paw under anesthesia. Ninety minutes after surgical incision, the deeply anesthetized rats were perfused transcardially with 4% paraformaldehyde. Serial 40-μm-thick sections of whole brain (except spinal cord) were cut and processed by immunohistochemistry to locate and quantify the sites and number of neurons with c-Fos immunoreactivity. Detection of c-Fos protein was performed using the peroxidase–antiperoxidase detection protocol. Our present study demonstrated that compared to control, administration of GBP (150 mg/kg, i.p.) before paw surgery significantly (p < 0.01) attenuated the incision-induced c-Fos expression only in the paraventricular nucleus of the hypothalamus. In addition, GBP-induced increase in c-Fos expression was observed in the dorsal raphe (DRN) and in the nucleus raphe magnus. Present results indicate that GBP may differentially modulate c-Fos expression in surgical paw incision. Moreover, this study provides some clue to examine whether GBP exerts its action simultaneously through two separate pathways in post-surgery.