JOURNAL ARTICLE

Gabapentin evoked changes in functional activity in nociceptive regions in the brain of the anaesthetized rat: an fMRI study

R J M Governo, P G Morris, C A Marsden, V Chapman
British Journal of Pharmacology 2008, 153 (7): 1558-67
18264121

BACKGROUND AND PURPOSE: Gabapentin (GBP; 1-(aminomethyl)cyclohexane acetic acid) is used clinically in the treatment of pain. Nevertheless, the sites and mechanisms of action of GBP are poorly defined. Herein, the effects of GBP on brain activation have been studied.

EXPERIMENTAL APPROACH: Changes in blood oxygen level dependent (BOLD) haemodynamic signal following intravenous infusion of GBP (equivalent to 30 mg kg(-1) p.o., followed by 100 mg kg(-1) p.o.), compared to saline control, were studied in isofluorane anaesthetized rats (n=8 per group). Effects of GBP on mean arterial blood pressure (MAP) were also recorded.

RESULTS: Random effect analysis revealed that the lower dose of GBP produced significant (P<0.001) increases in BOLD signal intensity in several brain regions, including the thalamus and periaqueductal grey (PAG), compared to basal. This dose of GBP also produced significant (P<0.001) decreases in BOLD signal intensity in the amygdala and the entorhinal cortex. Increasing the dose of GBP (100 mg kg(-1)) produced significantly greater changes in BOLD signal intensity in several brain regions including the thalamus and PAG. MAP was not significantly altered by GBP, compared to saline.

CONCLUSIONS AND IMPLICATIONS: GBP had marked positive and negative effects on BOLD signal intensity in a number of brain regions in naïve rats. The activation of key areas involved in nociceptive processing indicate a supraspinal site of action of GBP and this may contribute to its well-described analgesic effects in animal models of pain and clinical studies.

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