Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Department of Anesthesiology and Physiology & Pharmacology, WFSM, Winston-Salem, NC, USA.
Neuroscience. 2018 Jul 1;382:35-47. doi: 10.1016/j.neuroscience.2018.04.014. Epub 2018 Apr 22.
Psychosocial factors such as anxiety, depression and catastrophizing, commonly associated with established chronic pain, also may be associated with an increased risk of chronic postsurgical pain (CPSP) when present preoperatively. We used a repeat social defeat (RSD) paradigm to induce psychosocial stress in rodents prior to incisional surgery of the paw. Mixed effects growth curve models were utilized to examine resolution of mechanical hypersensitivity in rats for four weeks following surgery. Eight days following surgery, immunohistochemistry was conducted to examine glial activation as well as evoked neuronal activation in the spinal cord. Here we document that RSD resulted in reduced weight gain and increased depressive symptoms prior to surgery. Rats exposed to RSD displayed delayed resolution of mechanical hypersensitivity in the ipsilateral paw following surgery compared to non-defeated rats. Prior exposure to RSD significantly increased microglial activation and neuronal sensitization (pERK-IR) within the ipsilateral spinal cord. In conclusion, we found that chronic social stress alters the neurobiological response to surgical injury, resulting in slowed recovery. This model maybe useful for future interventional studies examining the mechanistic interactions between depression and risk of CPSP.
心理社会因素，如焦虑、抑郁和灾难化，通常与已确立的慢性疼痛相关，当它们在术前存在时，也可能与慢性术后疼痛（CPSP）的风险增加相关。我们使用重复社交挫败（RSD）范式在爪部切口手术前诱导啮齿动物的心理社会压力。混合效应生长曲线模型用于检查手术后四周大鼠机械性超敏反应的缓解情况。手术后 8 天，进行免疫组织化学检查以检查脊髓中的神经胶质激活和诱发神经元激活。在这里，我们记录到 RSD 在手术前导致体重增加减少和抑郁症状增加。与未被击败的大鼠相比，暴露于 RSD 的大鼠在手术后对侧爪的机械性超敏反应缓解延迟。先前暴露于 RSD 会显著增加同侧脊髓内的小胶质细胞激活和神经元敏化（pERK-IR）。总之，我们发现慢性社会压力改变了对手术损伤的神经生物学反应，导致恢复缓慢。这种模型可能对未来研究抑郁和 CPSP 风险之间的机制相互作用的干预研究有用。
