[Effect of electroacupuncture on cannabinoid-related receptor CB2R and TRPV1 and spinal microglial polarization in rats with primary dysmenorrhea].

OBJECTIVES

To observe the effect of electroacupuncture (EA) on the expression of cannabinoid receptor type 2 (CB2R), atypical cannabinoid receptor transient receptor potential vanilloid 1 (TRPV1), and spinal microglial polarization in rats with primary dysmenorrhea (PDM), so as to explore the underlying mechanism of EA alleviating PDM pain hyperalgesia.

METHODS

Thirty female SD rats were randomly divided into control, model, and EA groups (n=10 rats per group). The PDM model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin. Rats in the EA group were treated with EA (50 Hz) at "Guanyuan" (CV4) and bilateral "Sanyinjiao" (SP6) for 20 min, once a day for 10 consecutive days. The number of writhing, writhing score, and writhing latency were observed. The uterine histopathological changes were observed by H.E. staining. The contents of prostaglandin F2α (PGF2α), prostaglandin E2 (PGE2) in serum and interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in spinal cord were detected by ELISA. The protein expressions of CB2R and TRPV1 in spinal cord and uterus, and inducible nitric oxide synthase (iNOS) and arginase-1 (Arg1) in spinal cord were detected by Western blot.

RESULTS

Compared with the control group, the number and score of writhing, pathological injury score, contents of PGF2α and ratio of PGF2α/PGE2 in serum and IL-1β, TNF-α and IL-6 contents in spinal cord, the protein expressions of TRPV1 in both uterine and spinal cord, and iNOS in spinal cord were significantly increased in the model group (P<0.001), while contents of PGE2 in serum and IL-10 in spinal cord, the expression levels of CB2R in both uterine and spinal cord, and Arg1 in spinal cord were significantly decreased (P<0.001). In comparison with the model group, the number of writhing, pathological injury score, contents of PGF2α and ratio of PGF2α/PGE2 in serum and IL-1β, TNF-α and IL-6 contents in spinal cord, the protein expressions of TRPV1 in both uterine and spinal cord and iNOS in spinal cord were obviously decreased (P<0.001, P<0.05, P<0.01), whereas the writhing latency was considerably prolonged (P<0.05), with elevated contents of PGE2 in serum and IL-10 in spinal cord, and elevated protein expression levels of CB2R in both uterine and spinal cord, and Arg1 in spinal cord (P<0.01, P<0.001) in the EA group. H.E. staining showed degeneration, swelling, and necrosis of endometrial epithelial cells, dilation of glands, stromal hyperemia, and granulocyte infiltration in the model group, which were relatively milder in the EA group.

CONCLUSIONS

EA can alleviate uterine inflammatory response, pathological damage and pain sensitization in PDM rats, which may be related to activating peripheral and central CB2R expression, inhibiting TRPV1 expression, promoting spinal cord microglia polarization from M1 to M2, thus reducing neuroinflammation.