Eichwald Tuany, Talbot Sebastien
Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montreal, QC, Canada.
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Front Hum Neurosci. 2020 Jun 9;14:181. doi: 10.3389/fnhum.2020.00181. eCollection 2020.
The prevalence of obesity skyrocketed over the past decades to become a significant public health problem. Obesity is recognized as a low-grade inflammatory disease and is linked with several comorbidities such as diabetes, circulatory disease, common neurodegenerative diseases, as well as chronic pain. Adipocytes are a major neuroendocrine organ that continually, and systemically, releases pro-inflammatory factors. While the exact mechanisms driving obesity-induced pain remain poorly defined, nociceptor hypersensitivity may result from the systemic state of inflammation characteristic of obesity as well as weight surplus-induced mechanical stress. Obesity and pain also share various genetic mutations, lifestyle risk factors, and metabolic pathways. For instance, fat pads are often found hyper-innervated and rich in immune cell types of multiple origins. These immunocytes release cytokines, amplifying nociceptor function, which, in turn, via locally released neuropeptides, sustain immunocytes' function. Here, we posit that along with mechanical stress stemming from extra weight, the local neuro-immune interplay occurring within the fat pads maintains the state of chronic low-grade inflammation and heightens sensory hypersensitivity. Overall, stopping such harmful neuro-immune crosstalk may constitute a novel pathway to prevent obesity-associated comorbidities, including neuronal hypersensitivity.
在过去几十年中，肥胖症的患病率急剧上升，成为一个重大的公共卫生问题。肥胖被认为是一种低度炎症性疾病，与多种合并症相关，如糖尿病、循环系统疾病、常见的神经退行性疾病以及慢性疼痛。脂肪细胞是一个主要的神经内分泌器官，持续且系统性地释放促炎因子。虽然导致肥胖引起疼痛的确切机制仍不清楚，但伤害感受器超敏反应可能源于肥胖所特有的全身性炎症状态以及体重过剩引起的机械性应激。肥胖和疼痛还存在各种基因突变、生活方式风险因素以及代谢途径。例如，脂肪垫常常发现神经支配过度且富含多种来源的免疫细胞类型。这些免疫细胞释放细胞因子，增强伤害感受器功能，而伤害感受器功能又通过局部释放的神经肽维持免疫细胞的功能。在此，我们认为，除了额外体重产生的机械性应激外，脂肪垫内发生的局部神经 - 免疫相互作用维持了慢性低度炎症状态并加剧了感觉超敏反应。总体而言，阻断这种有害的神经 - 免疫串扰可能构成一条预防肥胖相关合并症（包括神经元超敏反应）的新途径。
