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Blood nerve barrier (BNB) disruption and edema are common in neuropathic pain as well as complex regional pain syndrome (CRPS). MicroRNAs (miRNA) are epigenetic multitarget switches controlling neuronal and non-neuronal cells in pain. The miR-183 complex attenuates hyperexcitability in nociceptors, but additional non-neuronal effects via transcription factors could contribute as well. This study explored exosomal miR-183 in CRPS and murine neuropathy, its effect on the microvascular barrier via transcription factor FoxO1 and tight junction protein claudin-5, and its antihyperalgesic potential. Sciatic miR-183 decreased after CCI. Substitution with perineural miR-183 mimic attenuated mechanical hypersensitivity and restored BNB function. In vitro, serum from CCI mice und CRPS patients weakened the microvascular barrier of murine cerebellar endothelial cells, increased active FoxO1 and reduced claudin-5, concomitant with a lack of exosomal miR-183 in CRPS patients. Cellular stress also compromised the microvascular barrier which was rescued either by miR-183 mimic via FoxO1 repression or by prior silencing of Foxo1. Perspective: Low miR-183 leading to barrier impairment via FoxO1 and subsequent claudin-5 suppression is a new aspect in the pathophysiology of CRPS and neuropathic pain. This pathway might help untangle the wide symptomatic range of CRPS and nurture further research into miRNA mimics or FoxO1 inhibitors.
Learn More >People with chronic pain engage in various strategies, such as pain catastrophizing and pain acceptance, to regulate the difficult emotional aspects of living with pain. Engagement in these strategies is known to influence pain severity and pain interference. However, less research has examined the extent to which general emotion regulation, the ability to identify emotions and engage in strategies to alter emotions, relates to pain-related outcomes. The current study, a large (N = 1453) online prospective study of adults with chronic pain, employed theory-driven assessment of emotion regulation to determine the extent to which general difficulties with emotion regulation at baseline relate to pain severity and pain interference at three-month follow-up, above and beyond pain catastrophizing and pain acceptance. We conducted a series of path models, controlling for demographic covariates and baseline pain severity and pain interference. Pain catastrophizing and pain acceptance at baseline significantly predicted pain interference at three-month follow-up. However, when indices of general emotion regulation were entered into the model, the associations between pain catastrophizing and pain interference (B = .009, p = .153) were no longer statistically significant. Alexithymia emerged as a significant predictor of pain severity (B = .012, p = .032) and pain interference (B = .026, p < .001). These findings highlight the value of considering the role of general emotion regulation (particularly identifying and describing emotions), in addition to pain-specific experiences, in understanding risk for poor pain-related outcomes. PERSPECTIVE: : In addition to pain catastrophizing and pain acceptance, difficulties regulating emotions in general (particularly elevated alexithymia) relates to pain outcomes three months later. These findings shed light on risk for poor pain outcomes and point to general emotion regulation as a potentially important target of chronic pain intervention.
Learn More >Studies have identified high rates of chronic postsurgical pain in adolescents. Characterizing patterns of pain in the transition from acute to chronic following major surgery may pinpoint critical periods of recovery. This observational study modelled pain trajectories over 1-year following surgery to attempt replication of prior work and evaluate baseline psychosocial factors and 12-month health outcomes. Adolescents 10-18 years completed electronic daily pain reporting for 7 days and self-reported health outcomes, at 5 assessment timepoints. Group-based trajectory modelling identified two trajectories with similar starting points in-hospital but distinct recovery courses at home. Pain declined steadily in one group across the study period ("Declining Pain"; estimated probability,18.9%), but pain increased after hospital discharge and remained high through 12-months in the other group ("High and Persistent Pain"; estimated probability,81.1%). Pre-surgery pain (aOR=1.86,p=0.001) and sleep quality (aOR=0.49,p=0.029) were associated with the High and Persistent pain trajectory in multivariate regressions. This trajectory was associated with lower total quality of life (B=-9.79,p=0.002), physical health (B=-15.93,p<0.001), psychosocial health (B=-6.73,p=0.06), and greater fatigue (B=-13.61,p=0.001). This study replicated prior findings identifying two post-surgical pain trajectories with diverging pain in the first two weeks. Clinical detection of those with increasing pain and early intervention may interrupt persistence of pain. PERSPECTIVE: . This article replicates a prior study identifying distinct post-surgical pain trajectories, Declining Pain and High and Persistent Pain. The High and Persistent pain trajectory is associated with pre-surgery pain, pre-surgery sleep quality, and lower quality of life (total, physical, and psychosocial health as well as fatigue) at 12-month follow-up.
Learn More >To address the ongoing opioid epidemic, there has been an increased focus on the treatment and evaluation of opioid use disorder (OUD). OUD and chronic pain (CP) frequently co-occur; however, little is known about the additional comorbidities that present when they occur together as compared to when either condition presents alone. Using data from Fiscal Year 2012 Veteran's Health Administration, all veterans diagnosed with both OUD + CP were compared to those diagnosed with OUD or CP alone on socioenvironmental characteristics, medical and mental health diagnoses, and Veterans Affairs (VA) clinical service use. Veterans with OUD + CP ( = 33,166), compared to those with OUD only (n = 12,517), had higher numbers of medical conditions. Compared to those with CP only ( = 2,015,368), veterans with OUD + CP had higher rates of homelessness and substance use diagnoses. Most mental health diagnoses, numbers of psychotropic medication fills, opioid prescriptions, and use of all other services were higher in the OUD + CP group than in either single disorder group. Multinomial regression analysis revealed stronger effects for medical disorders and medical-surgical outpatient service use in the comparison of OUD + CP with OUD only and stronger effects for substance use and mental health disorders and use of prescription opiates in the comparison with CP only. These findings suggest that concurrent OUD + CP imposes exceptional disease and clinical service burdens that likely require the development of simultaneous, integrated approaches to treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Learn More >To investigate the effects of a group-based cognitive behavioural intervention for patients with persistent low back pain (LBP) and psychological risk factors referred to secondary care.
Learn More >Evidence suggests insulin centrally activates the sympathetic nervous system, and a chemical stimulus to tissues activates the sympathetic nervous system via thin fibre muscle afferents. Insulin is reported to modulate putative chemical sensitive channels in the dorsal root ganglion neurons of these afferents. In the present study, we demonstrate that insulin potentiates the responsiveness of thin fibre afferents to capsaicin at muscle tissue levels as well as at the level of dorsal root ganglion neurons. In addition, we demonstrate that insulin augments the sympathetic nerve activity response to capsaicin in vivo. These data suggests that sympathoexcitation is peripherally mediated via insulin-induced chemical sensitization. The present study proposes a possible physiological role of insulin in the regulation of chemical sensitivity in somatosensory thin fibre muscle afferents.
Learn More >In addition to diurnal rhythms in physiology and behavior, a variety of pathological conditions also exhibit marked day-night changes in symptom intensity, exemplified by allergic rhinitis, arthritis, asthma, myocardial infarction, congestive heart failure, stroke, and chronic pain disorders. Currently, novel therapeutic approaches are facilitated by the development of chemical compounds targeted to key proteins that cause diurnal exacerbation of pathological events. Neuropathic pain is a chronic condition that occurs by tumor-induced nerve compression, cancer cell infiltration into the nerve, diabetes, and herpes virus infection. One troublesome hallmark symptom of neuropathic pain is hypersensitivity to normally innocuous stimuli known as "mechanical allodynia" that is often refractory to common analgesic therapies. Millions of patients worldwide presently endure neuropathic pain. We summarize the recent insights gained into the mechanism of diurnal exacerbation of neuropathic pain hypersensitivity and introduce the strategy of circadian clock-based drug development.
Learn More >Chronic pain (CP) commonly presents alongside psychiatric conditions such as depression, PTSD, and generalized anxiety. The current study sought to better understand this complex relationship by determining whether anxiety and depression symptom severity mediated the relationship between DSM-5 PTSD symptom clusters and pain symptoms in a sample of 663 Canadian Armed Forces (CAF) personnel and veterans seeking treatment for mental health conditions.
Learn More >The evaluation and treatment of patients with epilepsy is not limited to the type of epilepsy, but it must incorporate the common comorbid neurologic, psychiatric, and medical disorders, as the latter can bare an impact on the course and response to treatment of the seizure disorder and vice versa. In this article we review the bidirectional relations among epilepsy and two of its most common comorbidities, mood disorders and migraine and examine the implications of these relations on the selection of therapies of these three disorders and their response to treatment. We also review the most salient common pathogenic mechanisms that may explain such relations.
Learn More >This review discusses chronic pain, multiple modifiable lifestyle factors, such as stress, insomnia, diet, obesity, smoking, alcohol consumption and physical activity, and the relationship between these lifestyle factors and pain after cancer. Chronic pain is known to be a common consequence of cancer treatments, which considerably impacts cancer survivors' quality of life when it remains untreated. Improvements in lifestyle behaviour are known to reduce mortality, comorbid conditions (i.e., cardiovascular diseases, other cancer, and recurrence) and cancer-related side-effects (i.e., fatigue and psychological issues). An inadequate stress response plays an important role in dysregulating the body's autonomic, endocrine, and immune responses, creating a problematic back loop with pain. Next, given the high vulnerability of cancer survivors to insomnia, addressing and treating those sleep problems should be another target in pain management due to its capacity to increase hyperalgesia. Furthermore, adherence to a healthy diet holds great anti-inflammatory potential for relieving pain after cancer. Additionally, a healthy diet might go hand in hand with weight reduction in the case of obesity. Consuming alcohol and smoking have an acute analgesic effect in the short-term, with evidence lacking in the long-term. However, this acute effect is outweighed by other harms on cancer survivors' general health. Last, informing patients about the benefits of an active lifestyle and reducing a sedentary lifestyle after cancer treatment must be emphasised when considering the proven benefits of physical activity in this population. A multimodal approach addressing all relevant lifestyle factors together seems appropriate for managing comorbid conditions, side-effects, and chronic pain after cancer. Further research is needed to evaluate whether modifiable lifestyle factors have a beneficial influence on chronic pain among cancer survivors.
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