Pain
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Spinal high mobility group box 1 protein (HMGB1) plays crucial roles in arthritis-induced pain; however, the involvement of peripheral HMGB1 has not been examined previously. In this study, we addressed the role of peripheral HMGB1 and explored if sex contributes differentially to nociception in arthritis. We found Hmgb1 expression to be elevated in the ankle joints of male and female mice subjected to collagen antibody-induced arthritis. ⋯ We found that inhibition of resident macrophages attenuated HMGB1-induced pain-like behavior only in male mice. Interestingly, although the contribution of TLR4 on myeloid cells to nociception was minimal in females compared to males, TLR4 on nociceptors are important for HMGB1-induced pain in both sexes. Collectively, our work highlights sex- and cellular location-dependent roles of HMGB1 and TLR4 in peripheral pain mechanisms.
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Cognitive behavioral therapy (CBT) is a psychological intervention that involves development of coping strategies to reduce the experience of pain. Although CBT is a promising intervention to reduce headache days in patients with migraine, it may not be effective for all patients. Thus, there is a need to identify markers that could predict which patients will respond to CBT. ⋯ Greater reduction in headache days after CBT was related with less efficient CPM response before CBT at the trapezius (r = -0.492, P = 0.028) but not at the leg. This study found that headache reduction after CBT was related to right amygdala connectivity with frontal and sensorimotor regions at baseline as well as baseline pain modulation capacities. These findings suggest that individual differences in brain function and pain modulation can be associated with clinical improvements and help with determination of CBT responsiveness.
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Parents with chronic pain have a higher likelihood of having depression and anxiety and more often have children with these conditions. Depressive and anxious symptoms in children worsen pain-related disability and may be derived from exposure to their parents' symptoms. We assessed a model of intergenerational chronic pain-related disability that relies upon depressive and anxious symptoms of a mother and their child. ⋯ Worse maternal pain-related disability was associated with worse offspring pain-related disability (β = 0.20, 95% CI = 0.06-0.34). The mediation model indicated maternal and adolescent offspring symptoms of depression explained 36% of the relationship between maternal and offspring pain-related disability, with 11% explained by the intergenerational transmission of depression (serial mediation). We conclude that worse pain-related disability is associated between parent and child, and that depressive symptoms common to both mother and child play a key role in this relationship.
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Chronic neuropathic pain is frequently accompanied by memory impairment, yet the underlying mechanisms remain unclear. Here, we showed that mice displayed memory impairment starting at 14 days and lasting for at least 21 days after chronic constriction injury (CCI) of unilateral sciatic nerve in mice. Systemic administration of the pan histone deacetylase (HDAC) inhibitor sodium butyrate attenuated this memory impairment. ⋯ In addition, HDAC3 overexpression in the hippocampus led to memory impairment without affecting basal nociceptive responses in naive mice. Our findings suggest that HDAC3 contributes to memory impairment after CCI by impairing synaptic plasticity in hippocampus. Histone deacetylase 3 might serve as a potential molecular target for therapeutic treatment of memory impairment under neuropathic pain conditions.
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Frequent exposure to patient distress is associated with a higher prevalence of clinician distress and burnout. Patients with chronic pain often present with high levels of emotional distress. The current study examined the prevalence of burnout symptoms among a multidisciplinary sample of pain clinicians in Australia, the relationship between clinician confidence managing emotions and symptoms of burnout, and clinicians' perspectives on sources of stress and wellbeing at work. ⋯ Working with a multidisciplinary team and supportive relationships with colleagues were commonly reported sources of clinician wellbeing. The results of this study are discussed in light of previous reports of burnout in pain medicine physicians. Implications for clinician training in pain management and the prevention of burnout in pain clinicians are discussed.