The hippocampus is an important region
for the interaction between
depression and pain. Studies show that the P2X4 receptor plays key
role in neuropathic pain. This work investigated the potential implication
of the P2X4 receptor in the hippocampus in comorbidity of chronic
pain and depression. The rat model induced by chronic constriction
injury (CCI) plus unpredictable chronic mild stress (UCMS) was used
in this study. Our data showed that CCI plus UCMS treatment resulted
in abnormal changes in pain and depressive-like behaviors in the rat,
accompanied by the upregulated expression of P2X4, NLRP3 (NOD-like
receptor protein 3) inflammasome, and interleukin-1β and the
activation of p38 MAPK in the hippocampus. The P2X4 antagonist 5-BDBD
reversed these abnormal changes in the hippocampus, relieved hippocampal
neuronal damage, and alleviated the abnormal pain and depressive-like
behaviors in the CCI plus UCMS treated rats. These findings suggest
that the P2X4 receptor in the hippocampus may mediate and significantly
contribute to the pathological processes of comorbid pain and depression.
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