Central post-
stroke pain (CPSP), one of the complications of
cerebral ischemia and
neuropathic pain syndrome, is associated with specific somatosensory abnormalities. Although CPSP is a serious problem, detailed underlying mechanisms and standard treatments for CPSP are not well established. In this study, we assessed the role of GPR40, a long-chain
fatty acid receptor, showing anti-nociceptive effects, in CPSP. We also examined the role of astrocytes in CPSP due to their effects in mediating the release of
polyunsaturated fatty acids, which act as potential GPR40
ligands. The aim of this study was to determine the interactions between CPSP and astrocyte/GPR40 signaling. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). The development of hind paw
mechanical hyperalgesia was measured after BCAO using the von Frey test. Neuronal damage was estimated by histological analysis on day 3 after BCAO. The thresholds for hind paw
mechanical hyperalgesia were significantly decreased on days 1-28 after BCAO when compared with those of pre-BCAO assessments. BCAO-induced
mechanical hyperalgesia was significantly decreased by intracerebroventricular injection of
docosahexaenoic acid or
GW9508, a GPR40 agonist; furthermore, these effects were reversed by
GW1100, a GPR40 antagonist. The expression levels of
glial fibrillary acidic protein, an astrocytic marker, and some
free fatty acids were significantly decreased 5h after BCAO, although no effects of BCAO were noted on hypothalamic GPR40
protein expression. Our data show that BCAO-induced
mechanical hyperalgesia is possible to be regulated by astrocyte activation and stimulation of GPR40 signaling.