Open AccessPain modulatory network is influenced by sex and age in a healthy state and during osteoarthritis progression in rats
Author(s) -
Da Silva Joyce T.,
Tricou Christina,
Zhang Youping,
Tofighbakhsh Amir,
Seminowicz David A.,
Ro Jin Y.
Publication year - 2021
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13292
Subject(s) - periaqueductal gray , osteoarthritis , chronic pain , anterior cingulate cortex , nucleus accumbens , insula , sex characteristics , cingulate cortex , medicine , young adult , physiology , psychology , neuroscience , central nervous system , physical therapy , cognition , pathology , alternative medicine , midbrain
Abstract 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.