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The impact of anxiety on chronic musculoskeletal pain and the role of astrocyte activation.

ABSTRACT: Anxiety and depression are associated with increased pain responses in chronic pain states. The extent to which anxiety drives chronic pain, or vice versa, remains an important question that has implications for analgesic treatment strategies. Here, the effect of existing anxiety on future osteoarthritis (OA) pain was investigated, and potential mechanisms were studied in an animal model. Pressure pain detection thresholds, anxiety, and depression were assessed in people with (n = 130) or without (n = 100) painful knee OA. Separately, knee pain and anxiety scores were also measured twice over 12 months in 4730 individuals recruited from the general population. A preclinical investigation of a model of OA pain in normo-anxiety Sprague-Dawley (SD) and high-anxiety Wistar Kyoto (WKY) rats assessed underlying neurobiological mechanisms. Higher anxiety, independently from depression, was associated with significantly lower pressure pain detection thresholds at sites local to (P < 0.01) and distant from (P < 0.05) the painful knee in patients with OA. Separately, high anxiety scores predicted increased risk of knee pain onset in 3274 originally pain-free people over the 1-year period (odds ratio = 1.71; 95% confidence interval = 1.25-2.34, P < 0.00083). Similarly, WKY rats developed significantly lower ipsilateral and contralateral hind paw withdrawal thresholds in the monosodium iodoacetate model of OA pain, compared with SD rats (P = 0.0005). Linear regressions revealed that baseline anxiety-like behaviour was predictive of lowered paw withdrawal thresholds in WKY rats, mirroring the human data. This augmented pain phenotype was significantly associated with increased glial fibrillary acidic protein immunofluorescence in pain-associated brain regions, identifying supraspinal astrocyte activation as a significant mechanism underlying anxiety-augmented pain behaviour.

SUBMITTER: Burston JJ

PROVIDER: S-EPMC6407811 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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The impact of anxiety on chronic musculoskeletal pain and the role of astrocyte activation.

Burston James J JJ Valdes Ana M AM Woodhams Stephen G SG Mapp Paul I PI Stocks Joanne J Watson David J G DJG Gowler Peter R W PRW Xu Luting L Sagar Devi R DR Fernandes Gwen G Frowd Nadia N Marshall Laura L Zhang Weiya W Doherty Michael M Walsh David A DA Chapman Victoria V

Pain 20190301 3

Anxiety and depression are associated with increased pain responses in chronic pain states. The extent to which anxiety drives chronic pain, or vice versa, remains an important question that has implications for analgesic treatment strategies. Here, the effect of existing anxiety on future osteoarthritis (OA) pain was investigated, and potential mechanisms were studied in an animal model. Pressure pain detection thresholds, anxiety, and depression were assessed in people with (n = 130) or withou ...[more]

PMID: 30779717

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Project description:BackgroundMobile technologies are increasingly being used in health care and public health practice for patient communication, monitoring, and education. Mobile health (mHealth) tools have also been used to facilitate adherence to chronic musculoskeletal pain (CMP) management, which is critical to achieving improved pain outcomes, quality of life, and cost-effective health care.ObjectiveThe aim of this systematic review was to evaluate the 25-year trend of the literature on the adherence, usability, feasibility, and acceptability of mHealth interventions in CMP management among patients and health care providers.MethodsWe searched the PubMed, Cochrane CENTRAL, MEDLINE, EMBASE, and Web of Science databases for studies assessing the role of mHealth in CMP management from January 1999 to December 2023. Outcomes of interest included the effect of mHealth interventions on patient adherence; pain-specific clinical outcomes after the intervention; and the usability, feasibility, and acceptability of mHealth tools and platforms in chronic pain management among target end users.ResultsA total of 89 articles (26,429 participants) were included in the systematic review. Mobile apps were the most commonly used mHealth tools (78/89, 88%) among the included studies, followed by mobile app plus monitor (5/89, 6%), mobile app plus wearable sensor (4/89, 4%), and web-based mobile app plus monitor (1/89, 1%). Usability, feasibility, and acceptability or patient preferences for mHealth interventions were assessed in 26% (23/89) of the studies and observed to be generally high. Overall, 30% (27/89) of the studies used a randomized controlled trial (RCT), cohort, or pilot design to assess the impact of the mHealth intervention on patients' adherence, with significant improvements (all P<.05) observed in 93% (25/27) of these studies. Significant (judged at P<.05) between-group differences were reported in 27 of the 29 (93%) RCTs that measured the effect of mHealth on CMP-specific clinical outcomes.ConclusionsThere is great potential for mHealth tools to better facilitate adherence to CMP management, and the current evidence supporting their effectiveness is generally high. Further research should focus on the cost-effectiveness of mHealth interventions for better incorporating these tools into health care practices.Trial registrationInternational Prospective Register of Systematic Reviews (PROSPERO) CRD42024524634; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=524634.

Project description:ImportanceTick-borne diseases (TBDs) other than Lyme disease, such as spotted fever group rickettsiosis, ehrlichiosis, and galactose-α-1,3-galactose (α-gal) syndrome, are an emerging public health issue. Long-term sequelae secondary to Ehrlichia or Rickettsia infection are uncommon; however, musculoskeletal symptoms are often attributed to prior tick exposure.ObjectiveTo evaluate the potential associations between prior exposure to TBDs and musculoskeletal symptoms, including radiographic osteoarthritis.Design, setting, and participantsThis cross-sectional study analyzed serum samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing longitudinal, population-based study in Johnston County, North Carolina. Biospecimen testing and analysis were performed between May 2022 and November 2023. Participants in the JoCo OA project are noninstitutionalized White and Black Johnston County residents 45 years or older.Main outcome and measuresThe primary outcome was seropositivity with Ehrlichia IgG, Rickettsia IgG, and/or α-gal IgE and musculoskeletal symptoms. Secondary outcomes included risk factors associated with elevated α-gal IgE and weighted population point prevalence rates. Participants completed questionnaires, underwent physical assessments, and provided biospecimens for serological testing. Multivariable models were used to estimate associations of interest.ResultsOf the 605 participants who completed the fourth visit of the JoCo OA project, 488 (80.7%) had serum samples available for testing. The 488 participants had a median (IQR) age of 72 (68-78) years and included 336 females (68.9%) and 161 Black (33.0%) and 327 White (67.0%) individuals. The overall weighted point prevalence was 8.6% (95% CI, 5.9%-11.3%) for Ehrlichia IgG, 17.1% (95% CI, 12.6%-21.5%) for Rickettsia IgG, and 19.6% (95% CI, 15.3%-23.8%) for α-gal IgE level greater than 0.1 IU/mL. Only α-gal IgE was associated with knee pain, aching or stiffness (mean ratio, 1.30; 95% CI, 1.09-1.56). Antibodies to Rickettsia, Ehrlichia, and α-gal were not associated with symptomatic radiographic knee osteoarthritis. Male sex (odds ratio [OR], 2.63; 95% CI, 1.55-4.47), current smoker status (OR, 3.55; 95% CI, 1.38-9.18), and an attached tick bite in the past 5 years (OR, 3.99; 95% CI, 2.22-7.15) were all risk factors that were associated with α-gal IgE level greater than 0.1 IU/mL. Despite only 84 individuals (17.2%) recalling a tick bite in the past 5 years, 178 (36.5%) had evidence of prior tick-borne exposure, suggesting frequent human-tick interactions.Conclusions and relevanceResults of this cross-sectional study indicate no association between Ehrlichia or Rickettsia seropositivity and chronic musculoskeletal symptoms or osteoarthritis. Further investigation is needed into the pathogenesis of α-gal syndrome and interventions to reduce human-tick interactions.

Project description:BACKGROUND:Chronic musculoskeletal pain (MSP) is frequent in adolescents and has major medical and social consequences. In many cases, when no cause has been clearly established, this pain may be considered to be chronic idiopathic MSP. Our study seeks to identify general criteria for this type of pain through the experience of professionals from tertiary care centers with expertise in pediatric and adolescent chronic MSP. METHODS:Cross-sectional multicenter qualitative study. Semi-structured interviews of 25 professionals at a rheumatology reference center and in its network for pain management, including diverse specialists and professions. Interpretative Phenomenological Analysis is used to explore the data. RESULTS:This approach led us to identify 10 themes organized around three superordinate themes covering different stages of the diagnostic process: 1) the medical pain history up to the consultation at the reference center; 2) the professional's subjective feelings about the clinical presentation; 3) from the clinical examination to diagnosis and treatment of chronic idiopathic MSP. The main elements guiding this diagnosis do not come from the physical examination but from the medical history and the professionals' subjective feelings, that is, their clinical judgment. The professionals' impression of uneasiness and frustration, induced by patients and their parents, is of major importance. CONCLUSION:The principal elements guiding the diagnosis of chronic idiopathic MSP do not come primarily from the physical examination but rather from the pain history and the health professional's subjective feelings. Our results suggest that the concept of Juvenile Fibromyalgia (JFM) does not appear to cover all situations of chronic idiopathic MSP in adolescence. A constellation of non-organic criteria enables diagnosis of the latter; these criteria should be validated to avoid medical nomadism and multiple investigations and to shorten the interval until patients receive optimal pain management. CLINICAL TRIAL REGISTRATION:clinicaltrials.gov, NCT03171792, https://clinicaltrials.gov/ct2/show/NCT03171792?term=LACHAL&cntry=FR&city=paris&rank=1.

Project description:Study objectiveTo determine if baseline cytokines and their changes over postoperative days 0-2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery.DesignProspective, observational, longitudinal nested study.SettingUniversity-affiliated quaternary children's hospital.PatientsSubjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure.MeasurementsDemographics, surgical, psychosocial measures, pain scores, and opioid use over POD0-2 were collected. Cytokine concentrations were analyzed in serial blood samples collected before and after (up to two weeks) surgery, using Luminex bead arrays. After data preparation, relationships between pre- and post-surgical cytokine concentrations with acute (% time in moderate-severe pain over POD0-2) and chronic (pain score>3/10 beyond 3 months post-surgery) pain were analyzed. After adjusting for covariates, univariate/multivariate regression analyses were conducted to associate baseline cytokine concentrations with postoperative pain, and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes.Main resultsAnalyses included 3,164 measures of 16 cytokines from 112 subjects (median age 15.3, IQR 13.5-17.0, 54.5% female, 59.8% pectus). Acute postsurgical pain was associated with higher baseline concentrations of GM-CSF (β=0.95, SE 0.31; p=.003), IL-1β (β=0.84, SE 0.36; p=.02), IL-2 (β=0.78, SE 0.34; p=.03), and IL-12 p70 (β=0.88, SE 0.40; p=.03) and longitudinal postoperative elevations in GM-CSF (β=1.38, SE 0.57; p=.03), IFNγ (β=1.36, SE 0.6; p=.03), IL-1β (β=1.25, SE 0.59; p=.03), IL-7 (β=1.65, SE 0.7, p=.02), and IL-12 p70 (β=1.17, SE 0.58; p=.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (β= -0.39, SE 0.17; p=.02), and the risk of developing CPSP was elevated in patients with lower longitudinal postoperative concentrations of IL-6 (β= -0.57, SE 0.26; p=.03), IL-8 (β= -0.68, SE 0.24; p=.006), and IL-13 (β= -0.48, SE 0.22; p=.03). Furthermore, higher odds for CPSP were found for females (vs. males) for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNFα, and for pectus (vs. spine) surgery for IL-8 and IL-10.ConclusionWe identified pro-inflammatory cytokines associated with increased acute postoperative pain and anti-inflammatory cytokines associated with lower CPSP risk, with potential to serve as predictive and prognostic biomarkers.

Project description:BACKGROUND:In early autoimmune neuroinflammation, interferon (IFN)? and its upregulation of the immunoproteasome (iP) is pathologic. However, during chronic multiple sclerosis (MS), IFN? has protective properties. Although dysregulation of the iP has been implicated in neurodegeneration, its function remains to be fully elucidated. Here, we demonstrate that IFN? signaling in regional astrocytes induces the iP and promotes protection of the CNS during chronic autoimmunity. METHODS:In a multiple sclerosis (MS) brain, we evaluated mRNA expression and labeled postmortem MS brainstem and spinal cord for iP subunits and indicators of oxidative stress. Primary regional human astrocytes were analyzed for iP regulation and function by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, OxyBlot, and reactive oxygen species and caspase activity detection assays. Following immunization with myelin oligodendrocyte glycoprotein (MOG)35-55, the role of IFN? signaling and the iP during chronic experimental autoimmune encephalomyelitis (EAE) were assessed using pharmacologic inhibition of the iP and genetic interruption of IFN? signaling specifically in astrocytes. Central nervous system (CNS) tissues were analyzed by immunohistochemistry (IHC) and immunofluorescence, and cell-specific colocalization was quantified. RESULTS:In MS tissue, iP expression was enhanced in the spinal cord compared to brainstem lesions, which correlated with a decrease in oxidative stress. In vitro, IFN? stimulation enhanced iP expression, reduced reactive oxygen species burden, and decreased oxidatively damaged and poly-ubiquitinated protein accumulation preferentially in human spinal cord astrocytes, which was abrogated with the use of the iP inhibitor, ONX 0914. During the chronic phase of an MS animal model, EAE, ONX 0914 treatment exacerbated the disease and led to increased oxidative stress and poly-ubiquitinated protein buildup. Finally, mice with astrocyte-specific loss of the IFN? receptor exhibited worsened chronic EAE associated with reduced iP expression, enhanced lesion size and oxidative stress, and poly-ubiquitinated protein accumulation in astrocytes. CONCLUSIONS:Taken together, our data reveal a protective role for IFN? in chronic neuroinflammation and identify a novel function of the iP in astrocytes during CNS autoimmunity.

Dataset Information

The impact of anxiety on chronic musculoskeletal pain and the role of astrocyte activation.

Publications

The impact of anxiety on chronic musculoskeletal pain and the role of astrocyte activation.

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