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Pregnancy suppresses neuropathic pain induced by chronic constriction injury in rats through the inhibition of TNF-α

Authors Onodera Y, Kanao-Kanda M, Kanda H, Sasakawa T, Iwasaki H, Kunisawa T

Received 7 September 2016

Accepted for publication 24 January 2017

Published 8 March 2017 Volume 2017:10 Pages 567—574

DOI https://doi.org/10.2147/JPR.S121810

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Enrica Santarcangelo

Yoshiko Onodera, Megumi Kanao-Kanda, Hirotsugu Kanda, Tomoki Sasakawa, Hiroshi Iwasaki, Takayuki Kunisawa

Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan

Purpose: Pregnancy-induced analgesia develops during late pregnancy, but it is unclear whether this analgesia is effective against neuropathic pain. The detailed molecular mechanisms underlying pregnancy-induced analgesia have not been investigated. We examined the antinociceptive effect of pregnancy-induced analgesia in a neuropathic pain model and the expression of tumor necrosis factor (TNF)-α, glial fibrillary acidic protein (GFAP), Iba-1, and c-Fos in the spinal dorsal horn just before parturition.
Materials and methods: Female Sprague Dawley rats (200–250 g) were randomly assigned to one of four groups (pregnant + chronic constriction injury [CCI]; pregnant + sham injury; not pregnant + CCI; and not pregnant + sham injury). Separate groups were used for the behavioral and tissue analyses. CCI of the left sciatic nerve was surgically induced 3 days after confirming pregnancy in the pregnancy group or on day 3 in the not pregnant group. The spinal cord was extracted 18 days after CCI. TNF-α, GFAP, Iba-1, and c-Fos expression levels in the spinal dorsal horn were measured by Western blot analysis. Mechanical threshold was tested using von Frey filaments.
Results: The lowered mechanical threshold induced by CCI was significantly attenuated within 1 day before parturition and decreased after delivery. TNF-α expression in CCI rats was decreased within 1 day before parturition. Further, GFAP, Iba-1, and c-Fos expression in the spinal dorsal horn was reduced in the pregnant rats. Serum TNF-α in all groups was below measurable limits.
Conclusion:
Our findings indicate that pregnancy-induced analgesia suppresses neuropathic pain through reducing spinal levels of TNF-α, GFAP, Iba-1, and c-Fos in a rat model of CCI.

Keywords: pregnancy-induced analgesia, TNF-α, neuropathic pain, glial cell

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