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Melanocortin 4 Receptor Mediates Neuropathic Pain Through p38MAPK in Spinal Cord

Published online by Cambridge University Press:  02 December 2014

Haichen Chu ,
Jiangling Xia ,
Hongmei Xu ,
Zhao Yang ,
Jie Gao  and
Shihai Liu
Haichen Chu*
Affiliation:
Department of Anesthesiology, Affiliate Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China
Jiangling Xia
Affiliation:
Department of Anesthesiology, Affiliate Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China
Hongmei Xu
Affiliation:
Department of Anesthesiology, Affiliate Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China
Zhao Yang
Affiliation:
Qingdao Institute for Drug Control, Affiliate Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China
Jie Gao
Affiliation:
Department of Anesthesiology, Affiliate Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China
Shihai Liu
Affiliation:
Central Laboratory, Affiliate Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China
*
Department of Anesthesiology, Affiliate Hospital of Qingdao University Medical College, Qingdao 266003, Shandong Province, China. email: haichen0312@yahoo.com.cn
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Abstract

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Background:

Neuropathic pain is characterised by spontaneous ongoing or shooting pain and evoked amplified pain responses after noxious or non-noxious stimuli. Neuropathic pain develops as a result of lesions or disease affecting the somatosensory nervous system either in the periphery or centrally. Melanocortin 4 receptor (MC4R) plays an important role in the initiation of neuropathic pain but the underlying mechanisms are still unclear.

Methods:

Adult male Wistar rats were given chronic constriction injury (CCI) or sham operations. Part of CCI rats were intrathecally treated with HS014 (MC4R antagonist) or SB203580 (p38MAPK inhibitor). On the third, seventh and fourteenth day, the thermal threshold of operated paws was tested. In addition, the MC4R or phosphorylated p38MAPK (p-p38MAPK) levels of lumbar spinal cord were tested with ELISA (enzyme-linked immunosorbent assay), western blot and immunohistochemistry.

Results:

Here we demonstrate that (1) both HS014 and SB203580 reduced CCI reduced hyperalgesia (2) p-p38MAPK was increased after CCI with a time course parallel to that of the MC4R change, (3) The p38 activation was prevented by blocking MC4R with an antagonist HS014, but MC4R-IR was not prevented by SB203580. (4) MC4R and p-p38MAPK were located in the same cells.

Conclusion:

The mechanisms of neuropathic pain mediated by MC4R is related to the inhibition of p38MAPK activation. P38MAPK may be a downstream of MC4R.

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 39 , Issue 4 , July 2012 , pp. 458 - 464
Copyright
Copyright © The Canadian Journal of Neurological 2012

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