Proliferator-Activated Receptor-Gamma Coactivator-1α Haploinsufficiency Promotes Pain Chronification After Burn Injury

BACKGROUND: Tissue injuries such as surgery and trauma are usually accompanied by simultaneous development of acute pain, which typically resolves along with tissue healing. However, in many cases, acute pain does not resolve despite proper tissue repair; rather, it transitions to chronic pain. In this study, we examined whether proliferator-activated receptor-gamma coactivator-1α (PGC-1α), a master regulator of mitochondria biogenesis, is implicated in pain chronification after burn injury in mice. METHODS: We used PGC-1α+/+ and littermates PGC-1α+/− mice of both sex. Burn injury was induced on these mice. Hindpaw mechanical withdrawal thresholds and thermal withdrawal latency were examined. RESULTS: Hindpaw mechanical withdrawal thresholds and thermal withdrawal latencies were comparable at baseline between PGC-1α+/− and PGC-1α+/+ mice. After burn injury, both PGC-1α+/+ and PGC-1α+/− mice exhibited an initial dramatic decrease of withdrawal parameters at days 3 and 5 after injury. While PGC-1α+/+ mice fully recovered their withdrawal parameters to preinjury levels by days 11–14, PGC-1α+/− mice failed to recover those parameters during the same time frame, regardless of sex. Moreover, we found that PGC-1α+/− mice resolved tissue inflammation in a similar fashion to PGC-1α+/+ mice using a chemiluminescence-based reactive oxygen species imaging technique. CONCLUSIONS: Taken together, our data suggest that PGC-1α haploinsufficiency promotes pain chronification after burn injury. Accepted for publication January 16, 2019. J. Miao and X. Zhou contributed equally and share first authorship. The authors declare no conflicts of interest. Funding: J.M. is supported by R01DE02290 and R01DA039925. S.S. is supported by the Foundation of Anesthesia Education and Research, National Institute of General Medical Sciences R35-GM1286928, and research fund from the Department of Anesthesia, Critical Care and Pain Medicine at the Massachusetts General Hospital. Reprints will not be available from the authors. Address correspondence to Shiqian Shen, MD, Department of Anesthesia, Critical Care and Pain Medicine, Center for Translational Pain Research, Massachusetts General Hospital, Harvard Medical School, Jackson Bldg 458, 55 Fruit St, Boston, MA 02121. Address e-mail to sshen2@mgh.harvard.edu. © 2019 International Anesthesia Research Society

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