From the Department of Anesthesia, Critical Care and Pain Medicine, Center for Translational Pain Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Anesthesiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Anesth Analg. 2020 Jan;130(1):240-247. doi: 10.1213/ANE.0000000000004086.
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.
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.
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.
Taken together, our data suggest that PGC-1α haploinsufficiency promotes pain chronification after burn injury.
手术和创伤等组织损伤通常伴随着急性疼痛的同时发生，这种疼痛通常会随着组织愈合而消失。然而，在许多情况下，尽管组织得到了适当的修复，但急性疼痛并没有消失，而是转变为慢性疼痛。在这项研究中，我们研究了在烧伤后，作为线粒体生物发生主要调控因子的过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α）是否与小鼠的疼痛慢性化有关。
我们使用了 PGC-1α 和 PGC-1α 同窝仔鼠，这些仔鼠雌雄皆有。在这些仔鼠上诱导烧伤损伤。检测后爪机械缩足阈值和热缩足潜伏期。
在基线时，PGC-1α 和 PGC-1α 仔鼠的后爪机械缩足阈值和热缩足潜伏期相当。在烧伤损伤后，PGC-1α 和 PGC-1α 仔鼠在损伤后第 3 和第 5 天的缩足参数均有急剧下降。虽然 PGC-1α 仔鼠在 11-14 天内完全恢复到损伤前的水平，但在同一时间范围内，PGC-1α 仔鼠无法恢复这些参数，无论性别如何。此外，我们发现使用基于化学发光的活性氧成像技术，PGC-1α 仔鼠以与 PGC-1α 仔鼠相似的方式解决组织炎症。
综上所述，我们的数据表明 PGC-1α 杂合不足促进了烧伤后疼痛的慢性化。
