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


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.


CONCLUSIONS
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.
Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan.
Yoshiko
Y
Onodera
Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan.
Megumi
M
Kanao-Kanda
Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan.
Hirotsugu
H
Kanda
Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan.
Tomoki
T
Sasakawa
Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan.
Hiroshi
H
Iwasaki
Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan.
Takayuki
T
Kunisawa
TNF-α; glial cell; neuropathic pain; pregnancy-induced analgesia