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

Abstract

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: TNF-α; glial cell; neuropathic pain; pregnancy-induced analgesia.

Figure 1

The anti-allodynic effect of pregnancy in a rat model of CCI. Arrows indicate the time of pregnancy and surgery. The time-course of the anti-allodynic effects of pregnancy in rats with CCI. For comparison of the differences at individual time points between the four groups, we used Kruskal–Wallis and Dunn post hoc tests *P<0.05 pregnant sham vs non-pregnant CCI. **P<0.01 pregnant sham vs non-pregnant CCI. ^&P<0.05 non-pregnant sham vs non-pregnant CCI. ^&&P<0.01 non-pregnant sham vs non-pregnant CCI. ^#P<0.05 pregnant CCI vs non-pregnant CCI. Separate groups of rats were used for the behavioral test and tissue analysis. Abbreviation: CCI, chronic constriction injury.

Figure 2

Expression of TNF-α in the L4-5 spinal dorsal horn mediated by pregnancy in a CCI model. The CCI surgical procedure increased the expression of TNF-α in the spinal dorsal horn of the non-pregnant CCI group compared with the non-pregnant sham groups. Expression of TNF-α was reduced in the pregnant CCI group compared with the non-pregnant CCI group. Data were analyzed using Dunnett’s test, n=3. Abbreviations: CCI, chronic constriction injury; TNF, tumor necrosis factor.

Figure 3

Expression of GFAP in the L4-5 spinal dorsal horn mediated by pregnancy in a CCI model. The CCI surgical procedure increased the expression of GFAP in the spinal dorsal horn of the non-pregnant CCI group compared with the non-pregnant sham groups. Expression of GFAP was reduced in the pregnant CCI group compared with the non-pregnant CCI group. Data were analyzed using Dunnett’s test, n=3/group. Abbreviations: CCI, chronic constriction injury; GFAP, glial fibrillary acidic protein.

Figure 4

Expression of Iba-1 in the L4-5 spinal dorsal horn mediated by pregnancy in a CCI model. The CCI surgical procedure increased the expression of Iba-1 in the spinal dorsal horn of the non-pregnant CCI group compared with the non-pregnant sham groups. Expression of Iba-1 was reduced in the pregnant CCI group compared with the non-pregnant CCI group. Data were analyzed using Dunnett’s test, n=3/group. Abbreviation: CCI, chronic constriction injury.

Figure 5

Expression of c-Fos in the L4-5 spinal dorsal horn mediated by pregnancy in a CCI model. The CCI surgical procedure increased the expression of c-Fos in the spinal dorsal horn of the non-pregnant CCI group compared with the non-pregnant sham groups. Expression of Iba-1 was reduced in the pregnant CCI group compared with the non-pregnant CCI group. Data were analyzed using Dunnett’s test, n=3/group. Abbreviation: CCI, chronic constriction injury.