Pain
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Metabolic dysfunction has been suggested to be involved in musculoskeletal pain; however, few studies have identified metabolic markers associated with multisite musculoskeletal pain (MSMP). This study sought to identify metabolic marker(s) for MSMP by metabolomic analysis. The Tasmanian Older Adult Cohort Study (TASOAC) provided the discovery cohort with the Newfoundland Osteoarthritis Study (NFOAS) providing the replication cohort. ⋯ The significance remained in multivariable analysis (OR per log µM increase = 2.70, 95% confidence interval, 1.25-5.95). A total of 610 participants were included in the NFOAS, and the association with SM C18:1 was successfully replicated with 3 MSMP definitions (OR ranging from 1.89 to 2.82; all P < 0.03). Our findings suggest that sphingomyelin metabolism is involved in the pathogenesis of MSMP, and the circulating level of SM C18:1 could serve as a potential marker in the management of MSMP.
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Observational Study
Phenotyping peripheral neuropathic pain in male and female adolescents: pain descriptors, somatosensory profiles, conditioned pain modulation and child-parent reported disability.
Neuropathic pain (NeuP) can be difficult to diagnose and manage in children. Data regarding prevalence and sex-dependent differences are limited, and more detailed phenotyping is needed. This observational cohort study recruited adolescents (10-17 years) with NeuP or complex regional pain syndrome (CRPS). ⋯ Child-parent QoL scores correlated, but catastrophizing scores were discordant when parents or adolescents reported higher anxiety/depression. NeuP in adolescents is associated with significant pain, physical impairment, and psychosocial impairment. Quantifying alterations in somatosensory profiles, descending modulation, child and parent psychological function will inform individualized therapy and stratification for future clinical trials.
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Efficacy of treatment is heavily dependent on experience and expectations. Moreover, humans can generalize from one experience to a perceptually similar but novel situation. We investigated whether and how this applies to pain relief, using ecologically valid tonic pain stimuli treated by surreptitiously lowering the applied temperature. ⋯ Our data from 2 independent samples (N = 18 and N = 39) show a treatment experience effect, ie, for physically identical treatments, the initially superior physician was reported to deliver stronger pain relief. More importantly, the other faces on the perceptual continuum showed a graded effect of pain relief, indicating placebo generalization. Introducing a paradigm feasible to induce placebo pain relief, we show that the generic learning principle of generalization can explain carryover effects between learned and novel treatment situations.
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Adults are more likely to suffer from chronic pain than minors, and its underlying mechanism remains unclear. SIRT1 an important age-related protein with function of lifespan extension; whether SIRT1 plays a role in the different pain vulnerability of adult and juvenile remains unclear. Here, we found that the expression level of SIRT1 in dorsal root ganglia (DRG) was related to the pain vulnerability. ⋯ The different anti-inflammatory ability determined the different change trends of SIRT1 and ClC-3 trafficking contributed to the different pain vulnerability in adult and juvenile rodents. In addition, the serum SIRT1 level was negatively correlated with the pain score in patients with chronic pain. These findings revealed the mechanism of the difference in pain vulnerability between adult and juvenile rodents and provided evidence for age-specific treatment of chronic pain.
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Lateral and ventral lateral subregions of the periaqueductal gray (l/vlPAG) have been proved to be pivotal components in descending circuitry of itch processing, and their effects are related to the subclassification of neurons that were meditated. In this study, lateral parabrachial nucleus (LPB), one of the most crucial relay stations in the ascending pathway, was taken as the input nucleus to examine the modulatory effect of l/vlPAG neurons that received LPB projections. Anatomical tracing, chemogenetic, optogenetic, and local pharmacological approaches were used to investigate the participation of the LPB-l/vlPAG pathway in itch and pain sensation in mice. ⋯ Furthermore, chemogenetic and optogenetic activation of the LPB-l/vlPAG pathway resulted in both antipruritic effect and analgesic effect, whereas pharmacogenetic inhibition strengthened nociceptive perception without affecting spontaneous scratching behavior. Finally, in vivo pharmacology was combined with optogenetics which revealed that AMPA receptor-expressing neurons in l/vlPAG might play a more essential role in pathway modulation. These findings provide a novel insight about the connections between 2 prominent transmit nuclei, LPB and l/vlPAG, in both pruriceptive and nociceptive sensations and deepen the understanding of l/vlPAG modulatory roles in itch sensation by chosen LPB as source of ascending efferent projections.