Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
Health Sciences, Vancouver Island University, Nanaimo, Canada.
Neuroscientist. 2024 Oct;30(5):574-596. doi: 10.1177/10738584231176233. Epub 2023 May 22.
Chronic pain is highly prevalent and burdensome, affecting millions of people worldwide. Although it emerges at any point in life, it often manifests in adolescence. Given that adolescence is a unique developmental period, additional strains associated with persistent and often idiopathic pain lead to significant long-term consequences. While there is no singular cause for the chronification of pain, epigenetic modifications that lead to neural reorganization may underpin central sensitization and subsequent manifestation of pain hypersensitivity. Epigenetic processes are particularly active during the prenatal and early postnatal years. We demonstrate how exposure to various traumas, such as intimate partner violence while in utero or adverse childhood experiences, can significantly influence epigenetic regulation within the brain and in turn modify pain-related processes. We provide compelling evidence that the burden of chronic pain is likely initiated early in life, often being transmitted from mother to offspring. We also highlight two promising prophylactic strategies, oxytocin administration and probiotic use, that have the potential to attenuate the epigenetic consequences of early adversity. Overall, we advance understanding of the causal relationship between trauma and adolescent chronic pain by highlighting epigenetic mechanisms that underlie this transmission of risk, ultimately informing how to prevent this rising epidemic.
慢性疼痛普遍存在且负担沉重,影响着全球数百万人。尽管它可能在生命中的任何时候出现,但通常在青少年时期表现出来。鉴于青少年是一个独特的发展时期,与持续且往往是特发性疼痛相关的额外压力会导致严重的长期后果。虽然疼痛慢性化没有单一的原因,但导致神经重组的表观遗传修饰可能是中枢敏化和随后出现疼痛敏感性增加的基础。表观遗传过程在产前和出生后早期特别活跃。我们展示了暴露于各种创伤(如胎儿期的亲密伴侣暴力或不良的童年经历)如何能显著影响大脑内的表观遗传调节,并进而改变与疼痛相关的过程。我们提供了令人信服的证据表明,慢性疼痛的负担很可能在生命早期就开始了,通常是从母亲传给后代。我们还强调了两种有前途的预防策略,即催产素给药和益生菌使用,它们有可能减轻早期逆境的表观遗传后果。总的来说,我们通过强调潜在的风险传递的表观遗传机制,增进了对创伤与青少年慢性疼痛之间因果关系的理解,最终为预防这种日益严重的流行病提供了信息。