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Disparities in the experience of chronic musculoskeletal pain in the United States stem from a confluence of a broad array of factors. Organized within the National Institute on Aging Health Disparity Research Framework, a literature review was completed to evaluate what is known and what is needed to move chronic musculoskeletal pain research specific to disproportionately affected populations forward. Peer-reviewed studies published in English, on human adults, from 2000-2019, and conducted in the United States were extracted from PubMed and Web of Science. Articles were reviewed for key words that focused on underrepresented ethnic/race groups with chronic musculoskeletal pain applying health factor terms identified in the NIA Framework's four levels of analysis: 1) environmental, 2) sociocultural, 3) behavioral, and 4) biological. A total of 52 articles met inclusion criteria. There were limited publications specific to underrepresented ethnic/race groups with chronic musculoskeletal pain across all levels with particular research gaps under sociocultural and biological categories. Current limitations in evidence may be supplemented by a foundation of findings specific to the broader topic of "chronic pain" which provides guidance for future investigations. Study designs including a focus on protective factors and multiple levels of analyses would be particularly meritorious. PERSPECTIVE: Chronic musculoskeletal pain unequally burdens underrepresented ethnic/race groups. In order to move research forward and to systematically investigate the complex array of factors contributing toward health disparities, an organized approach is necessary. Applying the NIA Health Disparities Research Framework, an overview of the current state of evidence specific to chronic musculoskeletal pain and underrepresented ethnic/race groups is provided with future directions identified.
Learn More >Complex Regional Pain Syndrome (CRPS) is a musculoskeletal pain condition that often develops after limb injury and/or immobilization. Although the exact mechanisms underlying CRPS are unknown, the syndrome is associated with central and autonomic nervous system dysregulation and peripheral hyperalgesia symptoms. These symptoms also manifest in alcoholic neuropathy, suggesting that the two conditions may be pathophysiologically accretive. Interestingly, people assigned female at birth (AFAB) appear to be more sensitive to both CRPS and alcoholic neuropathy. To better understand the biobehavioral mechanisms underlying these conditions, we investigated a model of combined CRPS and alcoholic neuropathy in female rats. Animals were pair-fed either a Lieber-DeCarli alcohol liquid diet or a control diet for ten weeks. CRPS was modeled via unilateral hind limb cast immobilization for seven days, allowing for the other limb to serve as a within-subject control for hyperalgesia measures. To investigate the role of circulating ovarian hormones on pain-related behaviors, half of the animals underwent ovariectomy (OVX). Using the von Frey procedure to record mechanical paw withdrawal thresholds, we found that cast immobilization and chronic alcohol drinking separately and additively produced mechanical hyperalgesia observed 3 days after cast removal. We then examined neuroadaptations in AMPA GluR1 and NMDA NR1 glutamate channel subunits, extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) in bilateral motor and cingulate cortex across all groups. Consistent with increased pain-related behavior, chronic alcohol drinking increased GluR1, NR1, ERK, and CREB phosphorylation in the cingulate cortex. OVX did not alter any of the observed effects. Our results suggest accretive relationships between CRPS and alcoholic neuropathy symptoms and point to novel therapeutic targets for these conditions.
Learn More >Head-to-head comparator trials between first-line oral migraine preventatives and the new monoclonal antibodies (mAbs) blocking the calcitonin gene-related peptide (CGRP) pathway have not been published to date.
Learn More >Comorbid anxiety and depressive symptoms in chronic pain are a common health problem, but the underlying mechanisms remain unclear. Previously, we have demonstrated that sensitization of the central nucleus of the amygdala (CeA) neurons via decreased GABAergic inhibition contributes to anxiety-like behaviors in neuropathic pain rats. In this study, by using male Sprague-Dawley rats, we reported that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain. Bilateral electrolytic lesions of CeA but not lateral/basolateral nucleus of the amygdala (LA/BLA) abrogated both pain hypersensitivity and aversive and depressive symptoms of neuropathic rats induced by spinal nerve ligation (SNL). Moreover, SNL rats showed structural and functional neuroplasticity manifested as reduced dendritic spines on the CeA neurons and enhanced long-term depression (LTD) at the LA/BLA-CeA synapse. Disruption of GluA2-containing AMPARs trafficking and endocytosis from synapses using synthetic peptides, either pep2-EVKI or Tat-GluA2, restored the enhanced LTD at the LA/BLA-CeA synapse, and alleviated the mechanical allodynia and comorbid aversive and depressive symptoms in neuropathic rats, indicating that the endocytosis of GluA2-containing AMPARs from synapses is probably involved in the LTD at the LA/BLA-CeA synapse and the comorbid aversive and depressive symptoms in neuropathic pain in SNL-operated rats. These data provide a novel mechanism for elucidating comorbid aversive and depressive symptoms in neuropathic pain and highlight that structural and functional neuroplasticity in the amygdala may be important as a promising therapeutic target for comorbid negative emotional-affective disorders in chronic pain.Several studies have demonstrated the high comorbidity of negative affective disorders in patients with chronic pain. Understanding the affective aspects related to chronic pain may facilitate the development of novel therapies for more effective management. Here, we unravel that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain, and LTD at the amygdaloid LA/BLA-CeA synapse mediated by GluA2-containing AMPARs endocytosis underlies the comorbid aversive and depressive symptoms in neuropathic pain. This study provides a novel mechanism for elucidating comorbid aversive and depressive symptoms in neuropathic pain and highlights that structural and functional neuroplasticity in the amygdala may be important as a promising therapeutic target for comorbid negative emotional-affective disorders in chronic pain.
Learn More >Low back pain (LBP) is a very common health problem worldwide, and has a major impact on quality of life. This is a cross-sectional study using data obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) to investigate the health and nutritional status of Korean people, conducted in 2013, 2014, and 2015. The total of 8,473 patients included in the analysis. A 357 (19.34%) subjects in the chronic LBP group and 1,697 (25.61%) subjects in the no chronic LBP group reported no stress (P < 0.001). The numbers of subjects reporting mild, moderate, and severe stress in the two groups were 934 (50.6%) vs. 3,785 (57.11%), 432 (23.4%) vs. 910 (13.73%), and 123 (6.66%) and 235 (3.55%), respectively (all P < 0.001). Multiple logistic regression analysis with full adjustment for other variables indicated higher OR for severe stress (OR 2.82, P < 0.001) than moderate (OR 2.54, P < 0.001) and mild (OR 1.55, P < 0.001) stress. We confirmed that there was a significant association between chronic LBP and degree of stress. Therefore, the degree of stress should be assessed in clinical treatment of chronic LBP patients.
Learn More >: Identifying patients at risk for chronic musculoskeletal pain can inform evaluation and treatment decisions. The ability of physical therapists to assess patients' risk for chronic pain without use of validated tools has been questioned. The Ӧrebro Musculoskeletal Pain Questionnaire (OMPQ) is used to determine risk for chronic pain. The aim of this pragmatic study was to prospectively quantify the agreement between physical therapists' assessment of patients' risk for chronic symptoms compared to the OMPQ. Patients were asked to complete the OMPQ during the initial visit. Physical therapists, blinded to OMPQ risk classification, carried out their usual patient assessment procedures. The physical therapists rated patients as either high or low risk for chronic pain based on their clinical assessment. Agreement between therapist and OMPQ was determined using Cohen's Kappa (κ) and screening accuracy compared clinician risk to the OMPQ risk classification (reference standard) by way of contingency table analysis. Ninety-six (96) patients' risk classifications and 15 corresponding physical therapists' risk estimates were available for analysis. The OMPQ identified a 47% prevalence for high risk of chronic pain. Agreement (κ and 95% confidence interval) between physical therapist rating and OMPQ was slight, κ = 0.272 (0.033-0.421), = .026. Therapists' sensitivity and specificity (95% CI) for determining risk classifications were 60.0% (44.3-74.3) and 62.8% (48.1-75.6), respectively. The positive and negative likelihood ratios (95% CI) were 1.61 (1.05-2.47) and 0.64 (0.42-0.97). The use of validated self-report questionnaires are recommended to supplement clinician prognosis for patients at risk of chronic musculoskeletal pain.
Learn More >Neuropathic pain is a chronic condition with little specific treatment. Insulin-like growth factor 1 (IGF1), interacting with its receptor, IGF1R, serves a vital role in neuronal and brain functions such as autophagy and neuroinflammation. Yet, the function of spinal IGF1/IGF1R in neuropathic pain is unclear. Here, we examined whether and how spinal IGF1 signaling affects pain-like behaviors in mice with chronic constriction injury (CCI) of the sciatic nerve. To corroborate the role of IGF1, we injected intrathecally IGF1R inhibitor (nvp-aew541) or anti-IGF1 neutralizing antibodies. We found that IGF1 (derived from astrocytes) in the lumbar cord increased along with the neuropathic pain induced by CCI. IGF1R was predominantly expressed on neurons. IGF1R antagonism or IGF1 neutralization attenuated pain behaviors induced by CCI, relieved mTOR-related suppression of autophagy, and mitigated neuroinflammation in the spinal cord. These findings reveal that the abnormal IGF1/IGF1R signaling contributes to neuropathic pain by exacerbating autophagy dysfunction and neuroinflammation.
Learn More >Subcutaneous galcanezumab was an effective, well-tolerated preventive treatment for adults with episodic (EM) or chronic migraine (CM) in 4 phase 3 randomized controlled trials: EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER. Number needed to treat (NNT) and to harm (NNH) are metrics of effect size used to evaluate benefit-risk profiles. This study evaluated NNT, NNH, and benefit-risk profiles (measured as likelihood to be helped or harmed, LHH) of galcanezumab 120 mg versus placebo in patients with EM or CM.
Learn More >Interleukin-1β (IL-1β) plays a critical role in the development of neuropathic pain through activation of Schwann cells (SCs) after nerve injury. Here, we applied an RNA sequencing (RNA-seq) approach to identify the effect of IL-1β on gene signatures of a rat SC line (RSC96) and the potential molecular mechanisms underlying the development of neuropathic pain. RNA-seq data demonstrated a total of 57 significantly differentially expressed genes (DEGs) with 35 up-regulated and 22 down-regulated between SCs treated with IL-1β, and control SCs without treatment. Bioinformatics analysis showed that key upregulated DEGs included those associated with immune and inflammation-related processes, neurotrophin production and SC proliferation. Five proteins encoded by key upregulated DEGs (Ceacam1, Hap1, Irs3, Lgi4 and Mif) were further verified by Western blot. Consistent with the RNA-Seq results, the expression of key genes was confirmed in SCs by immunofluorescence of the chronic constriction injury (CCI) sciatic nerve in rats. Furthermore, we demonstrated that treatment with IL-1β resulted in an increase in p38/ERK phosphorylation, and activators of p38/ERK enhanced the effect of IL-1β on the expression some of the key genes, whereas p38/ERK inhibitors reversed these effects. In conclusion, the present study highlights key genes involved in the development of neuropathic pain through activation of SCs after nerve injury. Identification of these genes and subsequent evidence of their mediation by IL-1β treatment promote our understanding of molecular mechanisms of nerve injury induced neuropathic pain, and highlight potential molecular targets for the treatment of neuropathic pain.
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