Pain
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The social determinants of health (SDH) are known to differentially impact outcomes from many noncommunicable diseases; however, their potential role in low back pain (LBP) is poorly defined. This review endeavours to comprehensively inform the field of their relevance. Our research question was: "How do the broad range of SDH and chronic LBP (CLBP) relate?" The primary aim of this review was to synthesise evidence of relationships between SDH and the frequency or severity of CLBP. ⋯ We reported 166 relationships representing the majority of the PROGRESS domains. An array of independent and interdependent relationships between the SDH and CLBP were identified with the strongest evidence for associations related to educational attainment and socioeconomic status. Our findings suggest that greater recognition of the contribution of SDH to disparities in LBP outcomes is warranted and this has the potential to usefully inform strategies to impact burden.
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Children diagnosed with Christianson syndrome (CS), a rare X-linked neurodevelopmental disorder characterized by intellectual disability, epilepsy, ataxia, and mutism, also suffer from hyposensitivity to pain. This places them at risk of sustaining serious injuries that often go unattended. Christianson syndrome is caused by mutations in the alkali cation/proton exchanger SLC9A6/NHE6 that regulates recycling endosomal pH homeostasis and trafficking. ⋯ Behaviourally, Nhe6 KO mice have decreased nocifensive responses to acute noxious thermal, mechanical, and chemical (ie, capsaicin) stimuli. The reduced capsaicin sensitivity in the KO mice correlates with a decreased expression of the transient receptor potential channel TRPV1 at the plasma membrane and capsaicin-induced Ca influx in primary cultures of nociceptors. These data indicate that NHE6 is a significant determinant of nociceptor function and pain behaviours, vital sensory processes that are impaired in CS.
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Because treatment for postsurgical pain (PSP) remains a major unmet medical need, the emergence of safe and innovative nonopioid drugs has been strongly coveted. Tetrahydrobiopterin (BH4) is an interesting molecule for gaining a better understanding the pathological mechanism of neuropathic pain. However, whether BH4 and its pathway are involved in the pathogenesis of PSP remains unclear. ⋯ Furthermore, QM385, the SPR inhibitor, showed a significant dose-dependent, antinociceptive effect, which was supported by a reduction in BH4 levels in incised skin tissues, with no apparent adverse effects. Immunohistochemical analysis demonstrated that macrophages expressing GTPCH protein were increased around the injury site in the rat paw incision model. These results indicate that BH4 is involved in the pathogenesis of PSP, and that inhibition of the BH4 pathway could provide a new strategy for the treatment of acute PSP.