Pain
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Adolescent pain is common and continues into adulthood, leading to negative long-term outcomes including substance-related morbidity: an empirical definition of its construct may inform the early detection of persistent pain trajectories. These secondary analyses of a classical twin study assessed whether headaches, back pains, abdominal pain, chest pains, stabbing/throbbing pain, and gastric pain/nausea, measured in 501 pairs across 5 waves between age 12 and 17 years, fit a unitary construct or constitute independent manifestations. We then assessed which symptoms were associated with a steady, "frequent pain" trajectory that is associated with risk for early opioid prescriptions. ⋯ The highest area under the curve was attained by "back pain" at age 14 years (0.835); for multiple cut-off thresholds of symptom frequency, "back pain" showed good sensitivity/false alarm probability trade-offs, predominantly in the 13 to 15 years age range, to predict the "frequent pain" trajectory. These data support a unitary conceptualization and assessment of adolescent pain, which is advantageous for epidemiological, clinical, and translational purposes. Persistent back pain constitutes a sensitive indicator of a steady trajectory of adolescent pain.
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We deployed an online pain sensitivity questionnaire (PSQ) and an at-home version of the cold pressor test (CPT) in a large genotyped cohort. We performed genome-wide association studies on the PSQ score (25,321 participants) and CPT duration (6853). ⋯ Gene-based analysis followed by pathway analysis showed that genome-wide association studies results were enriched for genes expressed in the brain and involved in neuronal development and glutamatergic synapse signaling pathways. Finally, we confirmed that females with red hair were more sensitive to pain and found that genetic variation in the MC1R gene was associated with an increase in self-perceived pain sensitivity as assessed by the PSQ.
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High-molecular-weight hyaluronan (HMWH) is an agonist at cluster of differentiation (CD)44, the cognate hyaluronan receptor, on nociceptors, where it acts to induce antihyperalgesia in preclinical models of inflammatory and neuropathic pain. In the present experiments, we studied the CD44 second messengers that mediate HMWH-induced attenuation of pain associated with oxaliplatin and paclitaxel chemotherapy-induced peripheral neuropathy (CIPN). ⋯ Intradermal administration of inhibitors of CD44 second messengers, RhoA (member of the Rho family of GTPases), phospholipase C, and phosphatidylinositol (PI) 3-kinase gamma (PI3Kγ), attenuated HMWH-induced antihyperalgesia as does intrathecal administration of an ODN antisense to PI3Kγ. Our results demonstrated that HMWH induced antihyperalgesia in CIPN, mediated by its action at CD44 and downstream signaling by RhoA, phospholipase C, and PI3Kγ.
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The experience of pain and pain behaviors is not only determined by physiological but also psychosocial factors. In this context, the learning history of the individual and specifically operant reinforcement related to spouse responses might play an important role. We investigated the effect of a solicitous and habitually pain-reinforcing spouse for the processing of pain in patients with chronic pain. ⋯ This was specific for the painful stimulation at the back and occurred only in the presence but not the absence of the spouse. Pain ratings of intensity and unpleasantness were also higher in the patients with solicitous spouses when the spouse was present during painful stimulation. These data suggest that significant other responses indicative of operant reinforcement may have a direct effect on the cerebral processing of pain and related pain perception.
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