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Major depressive disorders (MDD) and chronic pain (CP) affect significant portion of the world's population and have high comorbidity rate. Social defeat stress (SDS) model was standardized in mice and can trigger depressive-like behavior and chronic pain. Based especially on clinical trials showing an effective preventive and therapeutic effect of physical exercise on CP and symptoms associated with MDD, this study aimed to investigate if the voluntary running wheel exercise can exert these effects in mice submitted to the 10-day SDS protocol, using fluoxetine as positive control. For this, we ran two set of experiments: in the first set mice started performing voluntary running wheel exercise after submitted to SDS and, in the second set, mice performed voluntary running wheel exercise before and during SDS. Mechanical and chemical hyperalgesia was analyzed through electronic von Frey and capsaicin test, respectively. Depressive-like behavior was assessed through social interaction test. Our results showed that the voluntary running wheel exercise was more effective than fluoxetine reversing the SDS-induced persistent hyperalgesia and both, fluoxetine and voluntary running wheel exercise, was effective reversing SDS-induced social avoidance. Also, voluntary running wheel exercise is an effective tool preventing both hyperalgesia and social avoidance induced by SDS. To the best of our knowledge, this was the first study using physical exercise as a therapeutic and preventive tool for chronic pain and depressive-like behavior simultaneously induced by social stress.
Learn More >Musculoskeletal (MSK) pain is frequently reported among adolescents and children and a common reason for consultation in primary care. Our aim is to examine its prevalence in 6-year old children in a general population and to assess associations with physical and psychosocial factors. Data from the Generation R Study, a population based cohort, was used. Prevalence and characteristics of MSK pain were assessed with parent-reported questionnaires at 6-years of age (N=6200). Demographics and data on physical activity, sedentary behaviors, previous reported MSK pain and behavioral problems were extracted from questionnaires. The BMI SD score was calculated from objectively measured weight and height. A three-month prevalence of 10.0% was found for MSK pain in children, of which one third was chronic, and 44.6% experienced together with pain at other sites. Univariate analyses showed that boys and children with lower socioeconomic status (SES) reported MSK pain more frequent compared to other pain and no pain. While no associations were found between MSK pain and children's BMI and physical activity level, children with MSK pain were more likely to watch television ≥2 hours/day. Multivariable analysis showed significant associations for MSK pain at 3 years of age (OR 5.10, 95% CI 3.25 to 7.98) and behavioral problems (OR 2.10, 95% CI 1.19 to 3.72) with the presence of MSK pain. So, MSK pain is already common in young children and is often chronic or recurrent. Previous reported MSK pain and behavioral problems are independently associated with MSK pain in the studied population.
Learn More >There is a significant unmet need for novel, effective, and well-tolerated acute migraine treatments. Remote electrical neuromodulation (REN) is a non-pharmacological, non-invasive, acute migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation – an endogenous analgesic mechanism in which a conditioning stimulation inhibits pain in remote body regions. This review presents the method of action and the clinical data of REN and discusses its potential patient benefits. The clinically meaningful efficacy, together with a very favorable safety profile, suggests that REN may offer a promising alternative for the acute treatment of migraine and could be considered first-line treatment in some patients.
Learn More >To examine opioid prescribing frequency and trends to Medicare Part D enrollees from 2013 to 2017 by medical specialty and provider type.
Learn More >This study aimed to analyze the associations among depressive/anxiety and pain symptoms in patients diagnosed with chronic pain.
Learn More >Chemotherapy induced peripheral neuropathy (CIPN), a toxic side effect of some cancer treatments, negatively impacts patient outcomes and drastically reduces survivor's quality of life (QOL). Uncovering the mechanisms driving chemotherapy-induced CIPN is urgently needed to facilitate the development of effective treatments, as currently there are none. Observing that C57BL/6 (B6) and 129SvEv (129) mice are respectively sensitive and resistant to Paclitaxel-induced pain, we investigated the involvement of the gut microbiota in this extreme phenotypic response. Reciprocal gut microbiota transfers between B6 and 129 mice as well as antibiotic depletion causally linked gut microbes to Paclitaxel-induced pain sensitivity and resistance. Microglia proliferated in the spinal cords of Paclitaxel treated mice harboring the pain-sensitive B6 microbiota but not the pain-resistant 129 microbiota, which exhibited a notable absence of infiltrating immune cells. Paclitaxel decreased the abundance of Akkermansia muciniphila, which could compromise barrier integrity resulting in systemic exposure to bacterial metabolites and products – that acting via the gut-immune-brain axis – could result in altered brain function. Other bacterial taxa that consistently associated with both bacteria and pain as well as microglia and pain were identified, lending support to our hypothesis that microglia are causally involved in CIPN, and that gut bacteria are drivers of this phenotype.
Learn More >Benefits of primary care provider (PCP) participation in pain management telementoring have been reported; however, no studies have examined within-patient changes in dose or discontinuation of long-term opioid therapy (LOT). The objectives of this nonrandomized study were to evaluate the relationship between telementoring participation and 1) LOT dose reduction and 2) LOT discontinuation and to 3) explore the relationship between LOT dose changes and patient-reported outcomes.
Learn More >Group III/IV muscle afferents transduce nociceptive signals and modulate exercise pressor reflexes (EPRs). However, the mechanisms governing afferent responsiveness to dually modulate these processes are not well characterized. We and others have shown that ischemic injury can induce both nociception-related behaviors and exacerbated EPRs in the same mice. This correlated with primary muscle afferent sensitization and increased expression of glial cell line-derived neurotrophic factor (GDNF) in injured muscle and increased expression of GDNF family receptor α1 (GFRα1) in dorsal root ganglia (DRG). Here, we report that increased GDNF/GFRα1 signaling to sensory neurons from ischemia/reperfusion-affected muscle directly modulated nociceptive-like behaviors and increased exercise-mediated reflexes and group III/IV muscle afferent sensitization. This appeared to have taken effect through increased cyclic adenosine monophosphate (cAMP) response element binding (CREB)/CREB binding protein-mediated expression of the purinergic receptor P2X5 in the DRGs. Muscle GDNF signaling to neurons may, therefore, play an important dual role in nociception and sympathetic reflexes and could provide a therapeutic target for treating complications from ischemic injuries.
Learn More >The aim of this systematic review was to summarize the effects of physical exercise on neuropathic pain (NP) in animal models of SCI. The search was conducted in Medline and Science Direct to identify experimental pre-clinical studies involving animal models of SCI, physical exercise as an intervention and the assessment of NP. Fifteen articles met the eligibility criteria. The review shows that in studies of NP involving animal models of SCI, rodents are the most common species. Thoracic contusion is the most common injury and mechanical and thermal nociception are the most frequently assessed NP components. The benefits of physical exercise vary according to its starting period and total duration. In addition, there is considerable heterogeneity regarding the type and intensity of exercise capable of alleviating NP after SCI. Furthermore, physical exercise has beneficial effects on mechanical, thermal and cold nociception, and spontaneous pain. These results are weakened by the paucity of studies involving these pain outcomes. The review protocol is published for free access on the SyRF platform (http://syrf.org.uk/protocols/).
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