Role of nicotinic acetylcholine receptors in alleviating central post–stroke pain in male mice

Central post–stroke pain (CPSP) is a frequent aftereffect in stroke patients; however, its underlying pathological mechanisms remain unclear. We previously demonstrated that transient ischemic stroke induced by bilateral common carotid artery occlusion (BCAO) produced mechanical allodynia in mice, which serves as a useful experimental model of CPSP. The present study investigated alterations in the expression of nicotinic acetylcholine (nACh) receptor subunits in the brain using this model. Immunohistochemical analyses revealed that the expression of the α4 subunit was significantly reduced in multiple brain regions of BCAO–induced CPSP model mice, including the cerebral cortex, thalamus, and hypothalamus, whereas that of the α7 subunit remained unchanged. Furthermore, a microinjection of the selective α4β2 nACh receptor agonist RJR–2403 into the lateral hypothalamus (LH) or anterodorsal thalamic nucleus (AD) significantly alleviated BCAO–induced mechanical allodynia. These results indicate that impaired neural signaling via α4–containing nACh receptors may contribute to the pathology of CPSP, and suggest the potential of α4β2 nACh receptors activation in the LH and AD as a therapeutic strategy for CPSP.