Changes in spinal A1 astrocyte polarization during peripheral inflammatory pain
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Department of Central Laboratory, Shanghai Children’s Hospital, Shanghai Jiaotong University, Shanghai 200040, China

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    Abstract:

    Objective Chronic inflammatory pain is a common disease that severely disrupts the quality of life of patients. The latest research shows that reactive astrocytes can be polarized to two different phenotypes, A1 and A2 astrocytes. Type A1 astrocytes can secrete pro-inflammatory cytokines and promote neuroinflammation, and type A2 astrocytes can secrete neurotrophic factors and promote tissue repair. This paper aimed to study pain behavior and changes to A1 astrocytes in the spinal cord of mice with peripheral inflammatory pain, to elucidate the pathological mechanisms of peripheral inflammatory pain. Methods A total of 16 male C57BL/ 6 mice were divided into the control group and inflammatory pain group (eight mice per group). The inflammatory pain model was established by injection of complete Freund′s adjuvant (CFA) into the plantar surface of the right hind paw. The control group were injected with an equivalent volume of saline. The mechanical withdrawal threshold (MWT) and the radiant heat stimulating paw withdrawal latency (PWL) of mice were measured before and 1, 3, 5 and 7 days after the CFA injection. Reverse transcription polymerase chain reaction was used to detect the expression of A1 and A2 astrocyte markers. Immunohistochemistry was used to detect the expression of glial fibrillary acidic protein ( GFAP) in the spinal dorsal horn to identify the process of astrocyte activation. Finally, the co-localization of A1 astrocyte marker C3 and GFAP in the spinal dorsal horn was detected. Results The ipsilateral MWT and PWL had both significantly decreased after CFA injection, indicating that the mice developed mechanical hyperalgesia and thermal hyperalgesia. At the third day after CFA injection, the expression levels of spinal GFAP were significantly increased compared to the day 0 (D0) group (1. 84 ± 0. 10 vs. 1. 08 ± 0. 22, respectively, P< 0. 05). On the 7th day after CFA injection, the mRNA levels of A1 astrocyte markers Serping1 and Lcn2 were increased vs. the D0 group (P<0. 05), and mRNA levels of A2 astrocyte markers S100a10 and Ptx3 were decreased vs. the D0 group (P<0. 05). The co-expression of C3 and GFAP in the spinal dorsal horn was increased in the CFA vs. D0 group (P<0. 05). Conclusions The reactive astrocytes in the spinal dorsal horn of mice with inflammatory pain were polarized to type A1, suggesting that A1 astrocytes may be involved in the development of inflammatory pain.

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History
  • Received:March 31,2021
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  • Online: December 03,2021
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