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Abstract. Introduction:. Prior research suggests that African Americans (AAs) have more frequent, intense, and debilitating pain and functional disability compared with non-Hispanic Whites (NHWs). Potential contributing factors to this disparity are physical activity and sedentary behavior, given that AAs are less physically active, and physical activity is associated with antinociception (whereas sedentary behavior is linked to pronociception). However, impact of these factors on pain processing has largely been unexplored in AAs, especially before chronic pain onset. Objective:. This study examined relationships between physical activity, sedentary behavior (sitting time), and laboratory measures of pain and pain modulation in adult AAs. These included heat pain threshold and tolerance, temporal summation of pain (TSP, a marker of central sensitization), and conditioned pain modulation (CPM, a marker of descending pain inhibition). Methods:. Multiple regressions were conducted to examine the effects of physical activity and sitting time on heat threshold and tolerance. Multilevel models were conducted to assess the relationship between physical activity, sitting time, and temporal summation of pain. Additional multilevel models were conducted to assess the relationship between physical activity, sitting time, and conditioned pain modulation. Results:. Higher level of physical activity, but not sitting time, was associated with reduced TSP slopes. Neither physical activity nor sitting time was associated with CPM slopes. No significant relationships between physical activity or sitting time and heat pain threshold or tolerance were detected. Conclusions:. These findings suggest that physical activity is associated with reduced TSP, an effect which may be driven by reduced spinal hyperexcitability in more active individuals. Thus, structural and individual interventions designed to increase physical activity in healthy, young AAs may be able to promote antinociceptive processes (ie, reduced TSP/reduced pain facilitation) potentially protective against chronic pain.

Abstract. To systematically identify and summarize possible subtypes of complex regional pain syndrome (CRPS), we searched MEDLINE, Embase, Cochrane, Scopus, and Web of Science for original studies reporting or investigating at least one subtype within a group of patients with CRPS. The search retrieved 4239 potentially relevant references. Twenty-five studies met our inclusion criteria and were included in the analysis. Complex regional pain syndrome phenotypes were investigated based on the following variables: clinical presentation/sensory disturbances, dystonia, skin temperature, disease duration, onset type, CRPS outcome, and neuropsychological test performance. Support was found for the following CRPS subtypes: CRPS type I, CRPS type II, acute CRPS, chronic CRPS, centralized CRPS, cold CRPS, warm CRPS, inflammatory CRPS, dystonic CRPS, nondystonic CRPS, familial CRPS, and nonfamilial CRPS. It is unclear whether these are distinct or overlapping subtypes. The results of this comprehensive review can facilitate the formulation of well-defined CRPS subtypes based on presumed underlying mechanisms. Our findings provide a foundation for establishing and defining clinically meaningful CRPS subtypes, with the ultimate goal of developing targeted and enhanced treatments for CRPS.

Objectives Accurately assessing the probability of significant respiratory depression following opioid administration can potentially enhance perioperative risk assessment and pain management. We developed and validated a risk prediction tool to estimate the probability of significant respiratory depression (indexed by naloxone administration) in patients undergoing noncardiac surgery.Design Retrospective cohort study.Setting Single academic centre.Participants We studied n=63 084 patients (mean age 47.1±18.2 years; 50% men) who underwent emergency or elective non-cardiac surgery between 1 January 2007 and 30 October 2017.Interventions A derivation subsample reflecting two-thirds of available patients (n=42 082) was randomly selected for model development, and associations were identified between predictor variables and naloxone administration occurring within 5 days following surgery. The resulting probability model for predicting naloxone administration was then cross-validated in a separate validation cohort reflecting the remaining one-third of patients (n=21 002).Results The rate of naloxone administration was identical in the derivation (n=2720 (6.5%)) and validation (n=1360 (6.5%)) cohorts. The risk prediction model identified female sex (OR: 3.01; 95% CI: 2.73 to 3.32), high-risk surgical procedures (OR: 4.16; 95% CI: 3.78 to 4.58), history of drug abuse (OR: 1.81; 95% CI: 1.52 to 2.16) and any opioids being administered on a scheduled rather than as-needed basis (OR: 8.31; 95% CI: 7.26 to 9.51) as risk factors for naloxone administration. Advanced age (OR: 0.971; 95% CI: 0.968 to 0.973), opioids administered via patient-controlled analgesia pump (OR: 0.55; 95% CI: 0.49 to 0.62) and any scheduled non-opioids (OR: 0.63; 95% CI: 0.58 to 0.69) were associated with decreased risk of naloxone administration. An overall risk prediction model incorporating the common clinically available variables above displayed excellent discriminative ability in both the derivation and validation cohorts (c-index=0.820 and 0.814, respectively).Conclusion Our cross-validated clinical predictive model accurately estimates the risk of serious opioid-related respiratory depression requiring naloxone administration in postoperative patients.

Abstract Migraine headache is a pain condition characterized by severe and recurrent unilateral head pain. Among other mechanisms, central pain sensitization processes seem to be involved in the disorder. An experimental protocol based on slowly repeated evoked pain (SREP) has been shown to indicate pain sensitization in fibromyalgia patients and differentiate these patients from healthy individuals and rheumatoid arthritis patients. This study examined SREP sensitization in migraine patients and explored its potential usefulness as a central sensitization marker. The SREP protocol was administered to 40 episodic migraine (EM) patients not currently experiencing a headache and 40 healthy controls. SREP consisted of a series of 9 suprathreshold painful pressure stimuli of 5 s duration and a 30 s interstimulus interval. SREP sensitization was indexed by the increase in pain ratings across the stimuli. Pain threshold, pain tolerance and temporal summation of pain were also assessed. SREP sensitization was observed in EM, but not in healthy individuals (p

Abstract. Introduction:. Chronic pain (CP) patients often display lower heart rate variability (HRV) and baroreceptor sensitivity (BRS), which are associated with increased evoked pain intensity and decreased pain tolerance. Objective:. The purpose of this study was to test whether the association between low levels of HRV and BRS and increased evoked pain responsiveness in individuals with CP is mediated by psychological distress and whether this mediation is sex dependent. Methods:. The sample consisted of 877 participants in Wave 6 of the Tromsø population study who reported clinically meaningful CP. Resting HRV and BRS parameters were derived from continuous beat-to-beat blood pressure recordings. Psychological distress was assessed using the Hopkins Symptom Checklist-10. After cardiovascular assessment, participants completed a 106-second cold pressor task (3°C bath), which assessed cold pressor pain intensity (CPI) and cold pressor pain tolerance (CPT). Results:. In the full CP sample, mediation analyses showed significant indirect effects, without direct effects, of HRV and BRS on both CPT and CPI via psychological distress. When stratified by sex, significant indirect effects via psychological distress were only found in males for the impact of rMSSD on CPT, the impact of SDNN on CPT, and the impact of BRS on CPT via psychological distress. Moderated mediation analyses revealed that there were no significant sex differences in the indirect effects of HRV and BRS on both CPT and CPI via psychological distress. Conclusions:. The hypoalgesic impact of cardiovascular regulatory systems on evoked pain responses is conveyed via the indirect effects of psychological distress.

Abstract. Introduction:. Acute stress reduces responses to static evoked pain stimuli (stress-induced analgesia [SIA]). Whether SIA inhibits temporal summation of pain, a dynamic evoked pain measure indexing central sensitization, has been little studied and mechanisms were not evaluated. Objectives:. We tested whether acute laboratory stressors reduce temporal summation and whether endogenous opioid (EO) mechanisms contributed. Methods:. Participants were 72 healthy individuals who attended 2 laboratory sessions, receiving either oral naltrexone (50 mg; opioid antagonist) or placebo (randomized, counterbalanced order). In each session, participants underwent a temporal summation protocol with evoked heat pain stimuli, once after extended rest and once after experiencing 2 acute stressors (public speaking and mental arithmetic challenge). Reduced temporal summation in the stress/pain relative to rest/pain condition indexed SIA. Results:. Analyses in the placebo condition indicated significant SIA on initial pain ratings but not temporal summation slope (index of central sensitization). This SIA effect was moderated by stress reactivity, with SIA only observed in high stress responders. Analyses comparing SIA across the drug conditions did not reveal any evidence of stress-related EO inhibition of temporal summation outcomes. Moderation analyses revealed that high, but not low, stress responders exhibited paradoxical analgesic effects of naltrexone on initial pain ratings but not temporal summation slopes. Independent of stress effects, significant EO inhibition of temporal summation slopes was observed, but only in females. Conclusions:. Results suggest that acute stress may reduce initial ratings in temporal summation protocols via nonopioid mechanisms but does not alter the temporal summation slope commonly used to index central sensitization.

Abstract Background US opioid prescribing and use escalated over the last two decades, with parallel increases in opioid misuse, opioid-related deaths, and concerns about diversion. Postoperatively prescribed opioids contribute to these problems. Policy makers have addressed this issue by limiting postoperative opioid prescribing. However, until recently, little data existed to guide prescribers on opioid needs postoperatively. This meta-analysis quantitatively integrated the growing literature regarding extent of opioids leftover after surgery and identified factors associated with leftover opioid proportions. Methods We conducted a meta-analysis of observational studies quantifying postoperative opioid consumption in North American adults, and evaluated effect size moderators using robust variance estimation meta-regression. Medline, EMBASE, Cumulative Index of Nursing and Allied Health Literature, and Cochrane Database of Systematic Reviews were searched for relevant articles published January 1, 2000 to November 10, 2018. The Methodological Index for Non-Randomized Studies (MINORS) tool assessed risk of study bias. The proportion effect size quantified the primary outcome: proportion of prescribed postoperative opioids leftover at the time of follow-up. Primary meta-regression analyses tested surgical type, amount of opioids prescribed, and study publication year as possible moderators. Secondary meta-regression models included surgical invasiveness, age, race, gender, postoperative day of data collection, and preoperative opioid use. Results We screened 911 citations and included 44 studies (13,068 patients). The mean weighted effect size for proportion of postoperative opioid prescriptions leftover was 61% (95% CI, 56-67%). Meta-regression models revealed type of surgical procedure and level of invasiveness had a statistically significant effect on proportion of opioids leftover. Proportion of opioids leftover was greater for “other soft tissue” surgeries than abdominal/pelvic surgeries, but did not differ significantly between orthopedic and abdominal/pelvic surgeries. Minimally invasive compared to open surgeries resulted in a greater proportion of opioids leftover. Limitations include predominance of studies from academic settings, inconsistent reporting of confounders, and a possible publication bias toward studies reporting smaller leftover opioid proportions. Conclusions and implications of key findings A significant proportion of opioids are leftover postoperatively. Surgery type and level of invasiveness affect postoperative opioid consumption. Integration of such factors into prescribing guidelines may help minimize opioid overprescribing while adequately meeting analgesic needs.

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition carrying substantial psychosocial burden. Psychological treatment for IC/BPS is little studied, and there are barriers to its use in clinical management. Whether psychological treatments benefit patients with IC/BPS is unclear and we do not know whether such treatments would meet patient needs. Aims: Incorporating patient-reported needs and acknowledging diversity in pain experiences can inform patient-centered interventions for IC/BPS. This project characterized the experience of living with IC/BPS and patient perceptions of needs in its treatment, with the goal of informing patient-centered treatment for IC/BPS. Methods: Using both quantitative and qualitative methods, 27 females with IC/BPS participated in a focus group and completed validated self-report assessments evaluating urinary symptoms, pain, and emotional functioning. Focus groups were audio recorded and transcribed and then coded and analyzed using an iterative inductive/deductive approach. Linear regression models evaluated the relationship between psychological functioning and symptom severity. Results: We conducted six focus groups between August and December 2017. Five major themes emerged from qualitative analysis: managing physical symptoms, emotional symptoms, impact on daily life and socio-contextual factors, responding to illness, and addressing needs in treatment. The physiological and emotional consequences of IC/BPS were reported, highlighting their impact on interpersonal relationships and challenges in obtaining appropriate treatment for IC/BPS. Quantitative analysis showed that depression levels were significantly associated with worsened IC/BPS symptomology, after controlling for known confounding factors. Conclusion: Individuals with IC/BPS could benefit from tailored psychological interventions focusing on pain management, emotion regulation, communications skills, along with sexual dysfunction and intimacy fears.

ObjectiveComplex regional pain syndrome (CRPS) is usually triggered by trauma or a surgical procedure, and it typically becomes an established one after an intense inflammatory process with chronic pain and edema as the main symptoms. Available treatments for CRPS have low efficacy. This study aimed to evaluate the clinical and immunoregulatory effects of omega-3 polyunsaturated fatty acid (PUFA) supplementation on paw edema and anti- and pro-inflammatory cytokines and macrophage phenotypes in the chronic post-ischemia pain (CPIP) preclinical model of CRPS-Type I.MethodsFemale Swiss mice were supplemented with omega-3, corn oil, or saline and then submitted to the CPIP model of ischemia/reperfusion (I/R) injury. Supplementation was carried out for 30 days prior to and up to 2 or 15 days after the induction of CPIP, according to experimental protocols. The supplementation protocol included 1,500 mg/kg of omega-3 or corn oil through an intragastric route (gavage). Paw edema, interleukin- (IL-) 4, IL-10, transforming growth factor-β1 (TGF-β1), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor (TNF) were then measured in the paw skin and muscle by enzyme-linked immunosorbent assay (ELISA), and macrophage phenotypes (M1 and M2) assessed in the paw muscle by Western blotting.ResultsThe CPIP model induced an increase in paw thickness up to 72 h post-I/R. Mice supplemented with omega-3 compared to the saline group displayed reduced edema but neither altered skin IL-4 or skin and muscle TGF-β1, TNF, and MCP-1 concentrations, nor did they exhibit significantly altered muscle macrophage phenotype on the 2nd-day post-CPIP. However, omega-3 supplementation reversed the I/R-related reduction in IL-4 in the paw muscle compared to groups supplemented with saline and corn oil. Furthermore, omega-3 promoted the reduction of IL-10 levels in the paw skin, compared to animals with lesions supplemented with saline, until the 2nd-day post-CPIP. On the 15th day post-CPIP, IL-10 was significantly increased in the muscle of animals supplemented with omega-3 compared to the saline group.ConclusionThe results suggest that omega-3 PUFA supplementation has anti-inflammatory effects in the CPIP model of CRPS-Type I, significantly reducing paw edema and regulating concentrations of anti-inflammatory cytokines, including IL-4 and IL-10.

Parental attitudes regarding pain interventions and perceptions of their child’s pain intensity likely influence the decision to administer postoperative analgesics. Our study examined the impact of daily fluctuations in child pain intensity and parental attitudes regarding complementary and alternative medicine (CAM) on analgesic administration following pediatric tonsillectomy. Parents of children undergoing tonsillectomy (n = 33) completed a survey assessing CAM attitudes and a 7-day postoperative electronic daily diary to record their child’s daily pain intensity and analgesic medications (acetaminophen, ibuprofen, or oxycodone). Generalized linear mixed models with Poisson distributions evaluated the effects of within-person (child’s daily pain intensity) and between-person (average postoperative pain, parental CAM attitudes) components on the number of medication doses administered. Higher daily pain intensity was associated with more oxycodone doses administered on a given day, but not acetaminophen or ibuprofen. Positive parental CAM attitudes were associated with less oxycodone use, beyond the variations accounted for by the child’s daily pain intensity and average postoperative pain. Both parental CAM attitudes and their child’s daily pain intensity were independently associated with parental decisions to administer opioids following tonsillectomy. Understanding factors influencing individual variability in analgesic use could help optimize children’s postoperative pain management.

BACKGROUND: Historically, in both adult and pediatric populations, a lack of knowledge regarding complex regional pain syndrome (CRPS) and absence of clear diagnostic criteria have contributed to the view that this is a primarily psychiatric condition.

Con el objetivo de explicar el estado de salud en el síndrome fibromiálgico (SFM) se exploran las relaciones entre cogniciones, afrontamiento centrado en la enfermedad y emociones. Asimismo, en este estudio ex post facto, se investiga el papel mediador del afrontamiento y las emociones entre las creencias de control (CC) y los resultados de salud. Se utilizó un modelo de ecuaciones estructurales. Participaron 315 pacientes con SFM de atención primaria y reumatología, que completaron medidas del estado de salud, creencias de control, afrontamiento, ansiedad y depresión. Los resultados mostraron que las CC que contienen el elemento de competencia (autoeficacia y competencia percibida en salud) tienen un efecto directo sobre todas las áreas del estado de salud; además, apoyaron el papel mediador de las emociones entre las creencias de competencia y el impacto físico y psicosocial, mientras que el afrontamiento únicamente medió la relación entre la autoeficacia y el impacto físico. Las CC y las emociones son elementos centrales en la explicación del impacto del SFM. Los esfuerzos terapéuticos deberían incrementar las creencias de competencia para mejorar significativamente los resultados de salud y el distrés emocional de la SFM. Estos hallazgos contribuyen al entendimiento sobre cómo los factores psicosociales influyen en la adaptación de pacientes con SFM.