Background Autonomic dysregulation may lead to blunted sympathetic reactivity in chronic pain states. Autonomic responses are controlled by the central autonomic network (CAN). Little research has examined sympathetic reactivity and associations with brain CAN structures in the presence of chronic pain; thus, the present study aims to investigate how chronic pain influences sympathetic reactivity and associations with CAN brain region volumes. Methods Sympathetic reactivity was measured as change in skin conductance level (ΔSCL) between a resting reference period and walking periods for typical and complex walking tasks (obstacle and dual-task). Participants included 31 people with (n = 19) and without (n = 12) chronic musculoskeletal pain. Structural 3 T MRI was used to determine gray matter volume associations with ΔSCL in regions of the CAN (i.e., brainstem, amygdala, insula, and anterior cingulate cortex). Results ΔSCL varied across walking tasks (main effect p = 0.036), with lower ΔSCL in chronic pain participants compared to controls across trials 2 and 3 under the obstacle walking condition. ΔSCL during typical walking was associated with multiple CAN gray matter volumes, including brainstem, bilateral insula, amygdala, and right caudal anterior cingulate cortex (p’s < 0.05). The difference in ΔSCL from typical-to-obstacle walking were associated with volumes of the midbrain segment of the brainstem and anterior segment of the circular sulcus of the insula (p’s < 0.05), with no other significant associations. The difference in ΔSCL from typical-to-dual task walking was associated with the bilateral caudal anterior cingulate cortex, and left rostral cingulate cortex (p’s < 0.05). Conclusions Sympathetic reactivity is blunted during typical and complex walking tasks in persons with chronic pain. Additionally, blunted sympathetic reactivity is associated with CAN brain structure, with direction of association dependent on brain region. These results support the idea that chronic pain may negatively impact typical autonomic responses needed for walking performance via its potential impact on the brain.

Cartilage endplate degeneration/calcification has been linked to the onset and progression of intervertebral disc degeneration and there is a critical need to understand mechanisms, such as hypertrophic differentiation, of cartilage endplate degeneration/calcification to inform treatment strategies for discogenic back pain.In vitro cell culture conditions capable of inducing hypertrophic differentiation are used to study pathophysiological mechanisms in articular chondrocytes, but culture conditions capable of inducing a hypertrophic cartilage endplate cell phenotype have yet to be explored. The goal of this study was to investigate the role of culture conditions capable of inducing hypertrophic differentiation in articular chondrocytes on hypertrophic differentiation in human cartilage endplate cells.Isolated human cartilage endplate cells were cultured as pellets for 21 days at either 5% O 2 (physiologic for cartilage) or 20.7% O 2 (hyperoxic) and treated with 10% fetal bovine serum or Wnt agonist, two stimuli used to induce hypertrophic differentiation in articular chondrocytes. Cartilage endplate cells did not exhibit a hypertrophic cell morphology in response to fetal bovine serum or Wnt agonist but did display other hallmarks of chondrocyte hypertrophy and degeneration such as hypertrophic gene and protein expression, and a decrease in healthy proteoglycans and an increase in fibrous collagen accumulation. These findings demonstrate that cartilage endplate cells take on a degenerative phenotype in response to hypertrophic stimuli in vitro, but do not undergo classical changes in morphology associated with hypertrophic differentiation regardless of oxygen levels, highlighting potential differences in the response of cartilage endplate cells versus articular chondrocytes to the same stimuli.

With age, susceptibility to osteoarthritis (OA) and OA-related pain and disability increases. Like in OA patients, gait patterns in rodent OA models shift to protect the injured limb during loading. However, unlike in OA patients, it is unknown how age affects gait changes in rodent OA models. In this study, gait compensations following meniscal injury in 3-, 6-, and 9-month-old rats were evaluated to examine ageeffects of OA-related joint dysfunction. Rats 3, 6, and 9 months received medial collateral ligament transection plus medial meniscus transection (MCLT + MMT) surgery (n = 8/age group) or a skin incision (n = 8/age group). Postsurgery, rats underwent gait testing at 2, 4, 6, and 8 weeks. Postmortem, joints were processed for histology to assess cartilage damage. MCLT + MMT rats walked with reduced vertical loading in their injured limbs immediately after injury and throughout OA progression. Compared to sham-operated limbs, 6-and 9-month MCLT + MMT animals reduced loading in their injured limbs while 3-month MCLT + MMT animals did not. MCLT + MMT rats also increased stance time on the injured limb compared to the contralateral limb. Additionally, for the MCLT + MMT animals, 6-and 9-month animals had significantly worse cartilage damage compared to 3-month animals. These data indicated age at injury onset affects how animals load the OA-affected joint, with older animals developing gait compensations that more markedly reduce weight on the injured limb during walking.

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