IL-36Ra inhibited A1 astrocyte polarization in spinal cord of mice subjected to inflammatory pain / 中国药理学通报

ABSTRACT

Aim To evaluate the effects of different doses of IL-36Ra on pain behavior and the polarization of spinal A1 astrocytes in mice with inflammatory pain.Methods A total of 32 male C57BL/6 mice were divided into four groups CFA+Saline group, CFA+IL-36Ra 50 ng group, CFA+IL-36Ra 100 ng group and CFA+IL-36Ra 200 ng group by random grouping.The inflammatory pain model was established by injection of complete Freund's adjuvant(CFA)into the plantar surface of the right hind paw of mice.The drugs were given daily from the 1st day to the 7th day after CFA injection in each group by intrathecal injection.The changes in the mechanical withdrawal threshold(MWT)and the radiant heat stimulating paw withdrawal latency(PWL)of the mice were detected before and 1, 3, 5 and 7 days after the CFA injection.Reverse transcription polymerase chain reaction was used to detect the expression changes of A1 and A2 astrocyte markers after IL-36Ra treatment.Immunohistochemistry was used to test the effect of IL-36Ra on the co-expression level of A1 astrocyte marker C3 and GFAP in the spinal dorsal horn.Results MWT and PWL of the ipsilateral paw significantly decreased after the CFA injection, and IL-36Ra(100 ng, 200 ng)treatment could significantly improve the mechanical allodynia and thermal hyperalgesia of CFA mice.After treatment for 7 days, IL-36Ra 200 ng successfully reversed the increase of GFAP and Lcn2 expression in the spinal cord of CFA mice, which demonstrated IL-36Ra could inhibit the activation of astrocytes.IL-36Ra significantly inhibited the expression of A1 astrocyte maker Serping1, H2-T23 in spinal cord but showed no effects on the expression of A2 astrocytes marker with each dose.Furthermore, IL-36Ra inhibited the expression of C3 within the astrocytes in the spinal dorsal horn of CFA mice.Conclusion IL-36Ra attenuates the inflammatory pain via inhibiting the polarization of A1 reactive astrocytes in the spinal cord of mice with inflammatory pain.