The contribution of astrocytes in the anterior cingulate cortex to the negative emotion and hyperalgesia under neuropathic pain

Junki Hashimoto 1, Hiroshi Ikeda1,2 , Kazuyuki Murase1,2

1Dept. of Human and Artificial Intelligence Systems, Grad. Sch. of Engineering, Univ. of Fukui, Japan
2Res. and Edu. Program Life Sci., Univ. of Fukui, Japan

Recent studies suggest that the activation of astrocytes in the anterior cingulate cortex (ACC) contribute to negative emotion under inflammatory pain. However, whether the astrocytes in the ACC contribute to the negative emotion under neuropathic pain is still unknown. In this study, we demonstrated that spared nerve injury (SNI) in mice induced hyperalgesia and also induced depression and anxiety-like behaviors which are measured by forced swimming test and elevated-plus maze test, respectively. The immunohistochemical staining revealed that the significant increase of intensity in GFAP and S100B immunoreactivity, which are astrocytic marker, in the ipsilateral ACC at 7 days after SNI. Moreover, intra-ACC injection of L-alpha-aminoadipate (L-α-AA, 10nmol), an astroglial toxin, inhibited the decrease of immobilization time in the forced swimming test and the time spent in the open arms in the elevated-plus maze test in mice subjected to SNI. The decrease of pain threshold measured by hot-plate test in mice subjected to SNI was also inhibited by injection of L-α-AA in the ACC. These results suggest that the activated astrocytes in the ACC are involved in the negative emotion and the hyperalgesia under neuropathic pain.