Pain
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Pain disparities based on race, sex, age, and socioeconomic status have been well documented. This study aimed to examine interactions among these sociodemographic factors on self-reported bodily pain in an urban community sample to assess whether membership in multiple at-risk groups confers greater risk for pain independent of depressive symptomatology. Participants (N = 1173) were enrolled in the epidemiological Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, and reported experiences of pain in various body sites. ⋯ Among those above the poverty line, African American (AA) men were less likely to report pain than White men (P = 0.024) and AA women (P = 0.019), potentially due to greater stoicism or coping skills and sources of resilience. Consistent with prior research, significant main effects revealed that older age (OR = 2.16, 95% CI [1.28-3.64], P = 0.004) and higher depressive symptoms (OR = 1.03, 95% CI [1.02-1.04], P < 0.001) were associated independently with increased likelihood of reporting pain. This study demonstrates that in an urban population, intersecting sociodemographic factors create unique social identities that impact pain, and emphasizes the need for identification of relevant mediational pathways.
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Pain and hypersensitivity months after peripheral injury reflect abnormal input from peripheral afferents likely in conjunction with central sensitization. We hypothesize that peripheral changes occur in defined sensory afferents and resolve as behavioral response to injury resolves. Male Sprague-Dawley rats underwent sham or partial L5 spinal nerve ligation, and paw withdrawal threshold (PWT) was sequentially measured during recovery. ⋯ After resolution of behavioral changes, several electrical abnormalities persisted in both neuronal subtypes. These data extend previous findings that mechanically sensitive nociceptors are sensitized, whereas tactile, largely Aβ afferents are desensitized after nerve injury by showing that the time course of resolution of these changes mirrors that of behavioral hypersensitivity in a surgical injury including neural damage. These data support a role of abnormal peripheral input, from both nociceptor and tactile afferents, during recovery from peripheral injury and underscore the potential importance of both classes of afferents as potential targets for pain treatment.
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Functional dyspepsia is a common functional gastrointestinal disorder. Gastric hypersensitivity (GHS) is a hallmark of this disorder, but the cellular mechanisms remain largely unknown. Stressors during gestational period could have effects on the offspring's tissue structure and function, which may predispose to gastrointestinal diseases. ⋯ A chromatin immunoprecipitation assay showed that PMS also enhanced the ability of NF-κBp65 to bind the promoter of Asic1 gene. Blockade of NF-κB using lentiviral-p65shRNA reversed upregulation of ASIC1 expression, GHS, and the hyperexcitability of DRG neurons. These data suggest that upregulation of ASIC1 expression is attributed to Asic1 promoter DNA demethylation and NF-κB activation, and that the enhanced interaction of the Asic1 and NF-κBp65 contributes to GHS induced by PMS.
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Mechanical allodynia is a cardinal sign of several inflammatory pain disorders where nerve growth factor, a prototypic neurotrophin, plays a crucial role by binding to TrkA receptors. Here, we took the advantage of our generated knock-in mouse model expressing a chimeric TrkA/TrkC receptor that seems to not specifically develop mechanical allodynia after inflammation, to identify the TrkA downstream pathways involved in this phenomenon. ⋯ Inflammatory reaction (oedema, IL-6 content), pain behaviours after intraplantar capsaicin, as well as TRPV1 calcium imaging response of dorsal root ganglion neurons were similar between TrkAC and WT mice. This deficiency in mechanical allodynia development in TrkAC mice is likely due to the alteration of the expression of different TrkA transduction pathways (ie, Akt, p38 MAPK, and c-Jun) especially p38 MAPK, in the dorsal root ganglion cell bodies, ultimately leading to an alteration of at least, ASIC3 channel overexpression, known to participate in nociceptor mechanosensory function.
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Randomized Controlled Trial Multicenter Study
Efficacy and safety of linaclotide for opioid-induced constipation in patients with chronic noncancer pain syndromes from a phase 2 randomized study.
Constipation is the most common adverse event (AE) of opioid therapy. This multicenter, phase 2 study evaluated the efficacy and safety of linaclotide in treating opioid-induced constipation (OIC) in patients with chronic noncancer pain syndromes (NCT02270983). Adults with OIC (<3 spontaneous bowel movements [SBMs]/week) related to chronic noncancer pain were randomized 1:1:1 to receive linaclotide 145 µg, linaclotide 290 µg, or placebo once daily for 8 weeks. ⋯ No serious AEs related to diarrhea were reported in any treatment group. Compared with placebo, linaclotide-treated patients had significant improvements in stool consistency, straining, abdominal bloating, and treatment satisfaction scores (P < 0.05). Linaclotide significantly improved OIC symptoms and was well tolerated in patients with chronic noncancer pain.