Department of Neural and Pain Sciences, School of Dentistry, University of Maryland Baltimore, Baltimore, Maryland, USA.
Center to Advance Chronic Pain Research, University of Maryland Baltimore, Baltimore, Maryland, USA.
Aging Cell. 2021 Feb;20(2):e13292. doi: 10.1111/acel.13292. Epub 2021 Jan 5.
Old age and female sex are risk factors for the development of osteoarthritis (OA) and chronic pain. We investigated the effects of sex and age on pain modulatory networks in a healthy state and during OA progression. We used functional MRI to determine the effects of sex and age on periaqueductal gray functional connectivity (PAG FC) in a healthy state (pre-OA) and during the early and late phases of monosodium iodoacetate-induced OA in rats. We then examined how sex and age affect longitudinal changes in PAG FC in OA. In a healthy state, females exhibited more widespread PAG FC than males, and this effect was exaggerated with aging. Young males had moderate PAG FC changes during the early phase but recruited additional brain regions, including the rostral anterior cingulate cortex (ACC), during the late phase. Young females exhibited widespread PAG FC in the early phase, which includes connections to insula, caudal ACC, and nucleus accumbens (NAc). Older groups had strong PAG FC with fewer regions in the early phase, but they recruited additional brain regions, including NAc, in the late phase. Overall, our findings show that PAG FC is modulated by sex and age in a healthy state. A widespread PAG network in the early phase of OA pain may contribute to the transition from acute to chronic OA pain and the increased risk of developing chronic pain for females. Enhanced PAG FC with the reward system may represent a potential mechanism underlying chronic OA pain in elderly patients.
衰老和女性是骨关节炎（OA）和慢性疼痛发展的危险因素。我们研究了性别和年龄对健康状态和 OA 进展过程中疼痛调节网络的影响。我们使用功能磁共振成像（fMRI）来确定性别和年龄对健康状态（OA 前）和单碘乙酸诱导的 OA 早期和晚期大鼠中导水管周围灰质功能连接（PAG FC）的影响。然后，我们研究了性别和年龄如何影响 OA 中 PAG FC 的纵向变化。在健康状态下，女性比男性表现出更广泛的 PAG FC，而这种影响随着年龄的增长而加剧。年轻男性在早期阶段 PAG FC 变化适中，但在晚期阶段招募了额外的大脑区域，包括额前扣带皮层（ACC）的前部。年轻女性在早期阶段表现出广泛的 PAG FC，包括与岛叶、ACC 的尾部和伏隔核（NAc）的连接。在早期阶段，年龄较大的组具有较强的 PAG FC，较少的区域，但在晚期阶段，他们招募了额外的大脑区域，包括 NAc。总的来说，我们的研究结果表明，PAG FC 在健康状态下受到性别和年龄的调节。OA 疼痛早期广泛的 PAG 网络可能有助于从急性到慢性 OA 疼痛的转变，以及女性发生慢性疼痛的风险增加。增强的 PAG FC 与奖励系统可能代表老年患者慢性 OA 疼痛的潜在机制。
