Effect of gabapentin on c-Fos expression in the CNS after paw surgery in rats.
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-microm-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.
Kazi
Jamil Ahsan
JA
Department of Anaesthesia, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore. anaajk@nus.edu.sg
Gee
Chen Fun
CF
D000588:Amines / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D000077206:Gabapentin; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology*; D006614:Hindlimb / Q000601:surgery*; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010149:Postoperative Pain / Q000517:prevention & control*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D016760:Proto-Oncogene Proteins c-fos; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin