Pain
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Alpha-1 adrenoceptors are overexpressed in the epidermis of a subgroup of patients with complex regional pain syndrome (CRPS). Activating α 1 -adrenoceptors in epidermal cells increases production of the proinflammatory cytokine interleukin-6 (IL-6), a mediator of inflammation. To investigate whether this might exacerbate inflammation in CRPS, primary keratinocytes or dermal fibroblasts were cultured from skin biopsies obtained from the affected limb of 25 patients and a similar site in 28 controls. ⋯ After α 1 -adrenoceptor stimulation of keratinocytes, increases in IL-6 mRNA but not protein were proportional to basal α 1 -adrenoceptor protein levels. Skin cells play an important role in persistent inflammation in CRPS. Potentially, a positive feedback loop between α 1 -adrenoceptors and IL-6 production in skin cells contributes to this inflammatory state.
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Epidemiological literature on the relationship between physical activity and chronic pain is scarce and inconsistent. Hence, our aim was to assess the relationship applying comprehensive methodology, including self-reported and accelerometer measures of physical activity and different severity levels of chronic pain. We used data from the Tromsø Study (2015-2016). ⋯ Robustness analyses gave similar results as the main analyses. We conclude that an inverse dose-response association between physical activity and chronic pain is consistent across measures. To summarize, higher levels of physical activity is associated with less chronic pain and moderate-to-severe chronic pain.
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Indifference or hypersensitivity? Solving the riddle of the pain profile in individuals with autism.
Excitatory-inhibitory (E/I) imbalance is a mechanism that underlies autism spectrum disorder, but it is not systematically tested for pain processing. We hypothesized that the pain modulation profile (PMP) in autistic individuals is characterized by less efficient inhibitory processes together with a facilitative state, indicative of a pronociceptive PMP. Fifty-two adults diagnosed with autism and 52 healthy subjects, age matched and sex matched, underwent quantitative sensory testing to assess the function of the (1) pain facilitatory responses to phasic, repetitive, and tonic heat pain stimuli and (2) pain inhibitory processes of habituation and conditioned pain modulation. ⋯ In conclusion, in line with the E/I imbalance mechanism, autism is associated with a pronociceptive PMP expressed by hypersensitivity to daily stimuli and experimental pain and less-efficient inhibition of tonic pain. The latter is an experimental pain model resembling clinical pain. These results challenge the widely held belief that individuals with autism are indifferent to pain and should raise caregivers' awareness of pain sensitivity in autism.
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The anterior cingulate cortex (ACC) processes the affective component of pain, whereas the primary somatosensory cortex (S1) is involved in its sensory-discriminative component. Injection of morphine in the ACC has been reported to be analgesic, and endogenous opioids in this area are required for pain relief. Mu opioid receptors (MORs) are expressed in both ACC and S1; however, the identity of MOR-expressing cortical neurons remains unknown. ⋯ Our results suggest a differential contribution of MOR-mediated modulation to ACC and S1 outputs. We also found that females had a greater density of MOR+ neurons compared with males in both areas. In summary, we conclude that MOR-dependent opioidergic signaling in the cortex displays sexual dimorphisms and likely evolved to meet the distinct function of pain-processing circuits in limbic and sensory cortical areas.
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Pain syndromes are often accompanied by complex molecular and cellular changes in dorsal root ganglia (DRG). However, the evaluation of cellular plasticity in the DRG is often performed by heuristic manual analysis of a small number of representative microscopy image fields. In this study, we introduce a deep learning-based strategy for objective and unbiased analysis of neurons and satellite glial cells (SGCs) in the DRG. ⋯ Changes in GS and GFAP levels could be linked to specific DRG neuron subgroups of different size. Hence, we could not detect gliosis but plasticity changes in the SGC marker expression. Our objective analysis of DRG tissue after peripheral nerve injury shows cellular plasticity responses of SGCs in the whole DRG but neither injury-induced neuronal death nor gliosis.