Rea Kieran, O' Mahony Siobhain M, Cryan John F
APC Microbiome Ireland, University College Cork, Cork, Ireland.
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
Neurobiol Pain. 2021 Feb 16;9:100061. doi: 10.1016/j.ynpai.2021.100061. eCollection 2021 Jan-Jul.
Within the human gut, we each harbour a unique ecosystem represented by trillions of microbes that contribute to our health and wellbeing. These gut microbiota form part of a complex network termed the microbiota-gut-brain axis along with the enteric nervous system, sympathetic and parasympathetic divisions of the autonomic nervous system, and neuroendocrine and neuroimmune components of the central nervous system. Through endocrine, immune and neuropeptide/neurotransmitter systems, the microbiota can relay information about health status of the gut. This in turn can profoundly impact neuronal signalling not only in the periphery, but also in the brain itself and thus impact on emotional systems and behavioural responses. This may be true for pain, as the top-down facilitation or inhibition of pain processing occurs at a central level, while ascending afferent nociceptive information from the viscera and systemic areas travel through the periphery and spinal cord to the brain. The endogenous cannabinoid receptors are ubiquitously expressed throughout the gut, periphery and in brain regions associated with pain responding, and represent targets for endogenous and exogenous manipulation. In this review, we will focus on the potential role of the endogenous cannabinoids in modulating microbiota-driven changes in peripheral and central pain processing. We also focus on the overlap in mechanisms whereby commensal gut microbiota and endocannabinoid ligands can regulate inflammation and further aim to exploit our understanding of their role in microbiota-gut-brain axis communication in pain processing.
在人类肠道内，我们每个人都拥有一个独特的生态系统，由数万亿微生物组成，这些微生物对我们的健康和幸福至关重要。这些肠道微生物群是一个复杂网络的一部分，该网络被称为微生物群 - 肠道 - 脑轴，它还包括肠神经系统、自主神经系统的交感和副交感神经分支，以及中枢神经系统的神经内分泌和神经免疫成分。通过内分泌、免疫和神经肽/神经递质系统，微生物群可以传递有关肠道健康状况的信息。这反过来不仅会深刻影响外周的神经元信号传导，还会影响大脑本身的神经元信号传导，从而影响情绪系统和行为反应。疼痛可能也是如此，因为疼痛处理的自上而下的促进或抑制发生在中枢水平，而来自内脏和全身区域的上行传入伤害性信息则通过外周和脊髓传递到大脑。内源性大麻素受体在整个肠道、外周以及与疼痛反应相关的脑区广泛表达，并代表了内源性和外源性调控的靶点。在这篇综述中，我们将重点关注内源性大麻素在调节微生物群驱动的外周和中枢疼痛处理变化中的潜在作用。我们还将重点关注共生肠道微生物群和内源性大麻素配体调节炎症的机制重叠，并进一步旨在利用我们对它们在疼痛处理中的微生物群 - 肠道 - 脑轴通信中的作用的理解。
