The journal of pain : official journal of the American Pain Society
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Orofacial pain is characterized by its easy spread to adjacent areas, thus presenting with primary hyperalgesia (hypersensitivity at the site of injury) and secondary hyperalgesia (extraterritorial hypersensitivity outside the injured zone). However, the mechanisms behind the secondary hyperalgesia are poorly understood. In the present study, we used a mouse model of partial transection of the infraorbital nerve (pT-ION) to study whether calcium channel subunit α2δ1 (Cavα2δ1) and its downstream signaling contributes to the development of secondary hyperalgesia in the orofacial area. pT-ION caused primary (V2 skin) and secondary (V3 skin) hyperalgesia, which was reversed by the Cavα2δ1 antagonist gabapentin and by the expression of Cavα2δ1-targeting interfering RNA in trigeminal ganglion (TG)-V3 neurons. pT-ION induced increased expression of PKC and TRPA1, which was reversed by Cavα2δ1-targeting interfering RNA, and PKC inhibition reversed the upregulation of TRPA1 and gap junction (GJ) proteins induced by pT-ION. ⋯ Thus, we conclude that Cavα2δ1 contributes to the development of secondary hyperalgesia through its downstream PKC-TRPA1/GJ signaling pathways. PERSPECTIVE: This study demonstrates that the activation of Cavα2δ1 and the downstream PKC-TRPA1/GJ signaling pathway contributes greatly to trigeminal nerve injury-induced secondary mechanical and cold hyperalgesia. This suggests that inhibitors of Cavα2δ1, TRPA1, or GJs might be effective treatments for nerve injury-induced spreading of orofacial pain.
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Review Meta Analysis
Systematic review and meta-analysis of genetic risk of developing chronic postsurgical pain.
Chronic postsurgical pain (CPSP) is a significant detriment to postsurgical recovery and a risk factor for prolonged opioid use. Emerging evidence suggests the estimated heritability for chronic pain is 45% and that genetic factors partially explain individual susceptibility to CPSP. The aim of this study was to systematically review, assess quality, and summarize the studies in humans that have investigated genetic factors associated with CPSP. ⋯ PERSPECTIVE: Our systematic review comprehensively describes 21 studies evaluating genetic association with CPSP, and limitations thereof. A meta-analysis of 6 variants (5 genes) found marginally increased risk for CPSP associated with rs734784 A>G of the potassium voltage-gated channel gene (KCNS1). Understanding genetic predisposition for CPSP will enable prediction and personalized management.
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This study determined the predictive capabilities of pain intensity and disability on health care utilization (number of condition-specific health care visits, incident, and chronic opioid use) and costs (total condition-specific and overall medical costs) in the year following an initial evaluation for musculoskeletal pain. We explored pain catastrophizing and spatial distribution of symptoms (ie, body diagram symptom score) as mediators of these relationships. Two hundred eighty-three military service members receiving initial care for a musculoskeletal injury completed a region-specific disability measure, numeric pain rating scale, Pain Catastrophizing Scale, and body pain diagram. ⋯ Higher pain intensity may drive more condition-specific health care utilization and use of opioids, while higher catastrophizing and larger spatial distribution of symptoms may drive higher costs for services received. PERSPECTIVE: This article examines underlying characteristics that help explain relationships between pain intensity and disability, and the outcomes of health care utilization and costs. Health care systems can use these findings to refine value-based prediction models by considering factors that differentially influence outcomes for health care use and cost of services.
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A growing pediatric and adult literature highlights the role of injustice appraisals in adjustment to pain. However, interpersonal injustice dynamics have remained largely unexplored. The present study investigated the factor structure and criterion validity of parentally adjusted versions of the Injustice Experience Questionnaire, assessing child-oriented (IEQ-Pc) and self-oriented appraisals (IEQ-Ps) in the context of child pain. ⋯ Current findings support the unique role of parental injustice appraisals, assessed by the IEQ-Pc and IEQ-Ps, in understanding child pain, but also suggest these may only partially capture the phenomenology of parental injustice appraisals in the context of child pain. PERSPECTIVE: This manuscript presents an examination of the construct and criterion validity of 2 parentally adjusted versions of the Injustice Experience Questionnaire. These measures could be valuable tools for clinicians in examining how parents respond to their child's pain as it impacts both the child's life and the parents'.