Department of Neural and Pain Sciences, School of Dentistry, Center to Advance Chronic Pain Research, University of Maryland Baltimore, Baltimore, MD, United States.
Department of Psychiatry, School of Medicine, Johns Hopkins University, Baltimore, MD, United States.
Pain. 2020 Jun;161(6):1371-1380. doi: 10.1097/j.pain.0000000000001810.
Endogenous pain inhibition is less efficient in chronic pain patients. Diffuse noxious inhibitory control (DNIC), a form of endogenous pain inhibition, is compromised in women and older people, making them more vulnerable to chronic pain. However, the underlying mechanisms remain unclear. Here, we used a capsaicin-induced DNIC test and resting-state functional MRI to investigate the impact of aging and sex on endogenous pain inhibition and associated brain circuitries in healthy rats. We found that DNIC was less efficient in young females compared with young males. Diffuse noxious inhibitory control response was lost in old rats of both sexes, but the brain networks engaged during DNIC differed in a sex-dependent manner. Young males had the most efficient analgesia with the strongest connectivity between anterior cingulate cortex (ACC) and periaqueductal gray (PAG). The reduced efficiency of DNIC in young females seemed to be driven by widespread brain connectivity. Old males showed increased connectivity between PAG, raphe nuclei, pontine reticular nucleus, and hippocampus, which may not be dependent on connections to ACC, whereas old females showed increased connectivity between ACC, PAG, and more limbic regions. These findings suggest that distinct brain circuitries including the limbic system may contribute to higher susceptibility to pain modulatory deficits in the elderly population, and sex may be a risk factor for developing age-related chronic pain.
内源性疼痛抑制在慢性疼痛患者中效率较低。弥散性伤害性抑制控制（DNIC）是一种内源性疼痛抑制形式，在女性和老年人中受到损害，使他们更容易患上慢性疼痛。然而，其潜在机制尚不清楚。在这里，我们使用辣椒素诱导的 DNIC 测试和静息态功能磁共振成像来研究年龄和性别对健康大鼠内源性疼痛抑制和相关脑回路的影响。我们发现，与年轻男性相比，年轻女性的 DNIC 效率较低。老年大鼠的 DNIC 反应均消失，但在性别依赖的方式下，参与 DNIC 的大脑网络不同。年轻男性的镇痛效果最有效，前扣带皮层（ACC）和中脑导水管周围灰质（PAG）之间的连接最强。年轻女性 DNIC 效率的降低似乎是由广泛的大脑连接驱动的。老年男性的 PAG、中缝核、桥脑网状核和海马之间的连接增加，这可能不依赖于与 ACC 的连接，而老年女性的 ACC、PAG 和更多边缘区域之间的连接增加。这些发现表明，包括边缘系统在内的不同脑回路可能导致老年人群对疼痛调节缺陷的更高易感性，而性别可能是导致与年龄相关的慢性疼痛的一个风险因素。
