肌筋膜性下腰痛大鼠模型中早年应激源影响的性别差异
Sex Differences in the Effects of Early Life Stressors in a Rat Model of Myofascial Low Back Pain.
作者信息
Singhal Deepika, Li Lin, Greffrath Wolfgang, Treede Rolf-Detlef
机构信息
Department of Neurophysiology, Mannheim Centre for Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang, China.
出版信息
Eur J Pain. 2025 Oct;29(9):e70114. doi: 10.1002/ejp.70114.
BACKGROUND
Chronic primary low back pain (cpLBP) is prevalent worldwide. Adverse childhood experiences (ACEs) increase the risk of cpLBP. Here, we explored ACEs as a predisposing factor for adult cpLBP using a rodent model.
METHODS
During adolescence, male and female Wistar rats underwent repeated restraint stress (RS) for one hour daily for 12 days or social isolation (SI) for 29 days; controls were handled daily. In adulthood, acute cpLBP was mimicked by NGF or saline injections into the lumbar multifidus muscle. Deep muscular hypersensitivity was assessed using the pressure pain threshold (PPT) of multifidus (MF) and gastrocnemius muscles (GS). Cutaneous mechanical hypersensitivity was measured with paw withdrawal threshold (PWT).
RESULTS
SI had smaller effects than RS in adolescence (d = -0.87 vs. -1.20) and adulthood (d = -0.33 vs. -0.48). RS and SI had a moderate impact in adolescent females (Cohen's d = -0.69), while males experienced a strong sensitisation (d = -1.42), with persistence into adulthood only in males (d = -0.52). Sensitivity to change was lower for PPT of GS (d = -0.71) than PPT of MF (d = -1.09) or PWT (d = -1.17). PPT of the injected MF dropped in stressed females both to saline (d = -0.447) and NGF (d = -0.568) but not in males. Both early life stress models induced immediate muscular and cutaneous hypersensitivity that recovered partly in adulthood.
CONCLUSIONS
Males were more susceptible to manifest sensitisation by stress than females, whereas females exhibited a memory trace (latent sensitisation), causing hyperalgesia upon the second hit in adulthood. The differential stress sensitivity may contribute to the higher prevalence of cpLBP in females.
SIGNIFICANCE STATEMENT
Chronic primary low back pain (cpLBP) is prevalent worldwide, particularly in women. Adverse childhood experiences (ACEs) increase the risk of cpLBP. Using a rat model of cpLBP and two early life stressors, we report that male rats were more susceptible to manifest sensitisation by stress, whereas female rats exhibited a memory trace, causing behavioural signs of hyperalgesia upon the second hit in adulthood (noxious muscle stimulation). The differential stress sensitivity may contribute to the higher prevalence of cpLBP in women.
背景
慢性原发性下腰痛（cpLBP）在全球范围内普遍存在。童年不良经历（ACEs）会增加患cpLBP的风险。在此，我们使用啮齿动物模型探讨ACEs作为成人cpLBP的诱发因素。
方法
在青春期，雄性和雌性Wistar大鼠每天接受1小时的重复束缚应激（RS），持续12天，或进行29天的社会隔离（SI）；对照组每天进行处理。成年后，通过向腰多裂肌注射神经生长因子（NGF）或生理盐水来模拟急性cpLBP。使用多裂肌（MF）和腓肠肌（GS）的压力疼痛阈值（PPT）评估深部肌肉超敏反应。用爪退缩阈值（PWT）测量皮肤机械性超敏反应。
结果
在青春期（效应量d = -0.87对-1.20）和成年期（d = -0.33对-0.48），SI的影响小于RS。RS和SI对青春期雌性有中度影响（科恩效应量d = -0.69），而雄性则有强烈的致敏作用（d = -1.42），且仅在雄性中持续到成年期（d = -0.52）。GS的PPT对变化的敏感性低于MF的PPT（d = -0.71）或PWT（d = -1.17）。在应激雌性中，注射NGF的MF的PPT下降至生理盐水组（d = -0.447）和NGF组（d = -0.568），但在雄性中未下降。两种早期生活应激模型均诱导了即时的肌肉和皮肤超敏反应，在成年期部分恢复。
结论
雄性比雌性更容易因应激而表现出致敏作用，而雌性表现出记忆痕迹（潜在致敏），在成年期受到二次刺激时会导致痛觉过敏。不同的应激敏感性可能导致cpLBP在女性中患病率较高。
意义声明
慢性原发性下腰痛（cpLBP）在全球范围内普遍存在，尤其是在女性中。童年不良经历（ACEs）会增加患cpLBP的风险。使用cpLBP大鼠模型和两种早期生活应激源，我们报告雄性大鼠更容易因应激而表现出致敏作用，而雌性大鼠表现出记忆痕迹，在成年期受到二次刺激（有害肌肉刺激）时会导致痛觉过敏的行为迹象。不同的应激敏感性可能导致cpLBP在女性中患病率较高。
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