A role for the purinergic receptor P2X(3) in astrocytes in the mechanism of craniofacial neuropathic pain

Abstract

The purinergic receptor P2X(3), expressed in the central terminals of primary nociceptive neurons in the brainstem, plays an important role in pathological pain. However, little is known about expression of P2X(3) in the brainstem astrocytes and its involvement in craniofacial pathologic pain. To address this issue, we investigated the expression of P2X(3) in astrocytes in the trigeminal caudal nucleus (Vc) in a rat model of craniofacial neuropathic pain, chronic constriction injury of infraorbital nerve (CCI-ION). We found that 1) P2X(3)-immunoreactivity is observed in the brainstem astrocytes, preferentially in their fine processes, 2) the number of P2X(3)-positive fine astrocytic processes and the density of P2X(3) in these processes were increased significantly in CCI-ION rats, compared to control rats, and 3) administration of MPEP, a specific mGluR5 antagonist, alleviated the mechanical allodynia and abolished the increase in density of P2X(3) in fine astrocytic processes caused by CCI-ION. These findings reveal preferential expression of P2X(3) in the fine astrocytic processes in the brainstem, propose a novel role of P2X(3) in the fine astrocytic process in the mechanism of craniofacial neuropathic pain, and suggest that the expression of astrocytic P2X(3) may be regulated by astrocytic mGluR5.