Osborne Natalie R, Cheng Joshua C, Rogachov Anton, Kim Junseok Andrew, Hemington Kasey S, Bosma Rachael L, Inman Robert D, Davis Karen D
Division of Brain, Imaging, and Behaviour, Krembil Brain Institute, Krembil Research Institute, University Health Network, Toronto, ON, Canada.
Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Pain. 2021 Jan;162(1):97-108. doi: 10.1097/j.pain.0000000000002016.
The subgenual anterior cingulate cortex (sgACC) plays an important role in pain modulation. We previously demonstrated sex differences in sgACC functional connectivity (FC) in healthy individuals. Given that many chronic pain conditions show sex differences in prevalence, here we tested the hypothesis that people with chronic pain exhibit a sex-specific pattern of abnormal sgACC FC. We acquired resting-state functional magnetic resonance imaging data from 156 (82 W: 74 M) healthy participants and 38 (19 W: 19 M) people with chronic low back pain resulting from ankylosing spondylitis, a condition that predominantly affects men. We confirmed that there are sex differences in sgACC FC in our large cohort of healthy adults; women had greater sgACC FC with the precuneus, a key node of the default mode network, and men had greater sgACC FC with the posterior insula and the operculum. Next, we identified an interaction effect between sex and pain status (healthy/chronic pain) for sgACC FC. Within the chronic pain group, women had greater sgACC FC than men to the default mode and sensorimotor networks. Compared to healthy women, women with chronic pain also had greater sgACC FC to the precuneus and lower FC to the hippocampus and frontal regions. No differences in sgACC FC were seen in men with vs without chronic pain. Our findings indicate that abnormal sgACC circuitry is unique to women but not men with ankylosing spondylitis-related chronic pain. These sex differences may impact the benefit of therapeutics that target the sgACC for chronic pain.
膝下前扣带回皮质（sgACC）在疼痛调节中起重要作用。我们之前证明了健康个体中sgACC功能连接（FC）存在性别差异。鉴于许多慢性疼痛疾病在患病率上存在性别差异，在此我们检验了以下假设：慢性疼痛患者表现出sgACC FC异常的性别特异性模式。我们获取了156名（82名女性：74名男性）健康参与者以及38名（19名女性：19名男性）患有强直性脊柱炎导致的慢性下腰痛患者的静息态功能磁共振成像数据，强直性脊柱炎主要影响男性。我们证实在我们这个庞大的健康成年人群体中sgACC FC存在性别差异；女性与默认模式网络的关键节点楔前叶的sgACC FC更强，而男性与后岛叶和岛盖的sgACC FC更强。接下来，我们确定了sgACC FC在性别与疼痛状态（健康/慢性疼痛）之间的交互作用。在慢性疼痛组中，女性与默认模式和感觉运动网络的sgACC FC比男性更强。与健康女性相比，慢性疼痛女性与楔前叶的sgACC FC也更强，而与海马体和额叶区域的FC更低。患有和未患有慢性疼痛的男性在sgACC FC上未见差异。我们的研究结果表明，sgACC回路异常是患有强直性脊柱炎相关慢性疼痛的女性而非男性所特有的。这些性别差异可能会影响针对sgACC治疗慢性疼痛的疗效。
