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Despite decades of research on the identification of specific characteristics of situations that trigger a physiological stress response (novelty, unpredictability, threat to the ego, and sense of low control [NUTS]), no integrative research has examined the validity of this framework applied to pain experiences. This study aimed to 1) explore the stressful characteristics of pain among individuals living with chronic pain and 2) examine whether the NUTS framework comprehensively captures the stressful nature of pain.
Learn More >The worldwide diabetes epidemic is estimated to currently afflict almost 500 million persons. Long-term diabetes damages multiple organ systems with the blood vessels, eyes, kidneys and nervous systems being particularly vulnerable. These complications of diabetes reduce lifespan, impede quality of life and impose a huge social and economic burden on both the individual and society. Peripheral neuropathy is a debilitating complication that will impact over half of all persons with diabetes. There is no treatment for diabetic neuropathy and a disturbingly long history of therapeutic approaches showing promise in preclinical studies but failing to translate to the clinic. These failures have prompted re-examination of both the animal models and clinical trial design. This review focuses on the functional and structural parameters used as indices of peripheral neuropathy in preclinical and clinical studies and the extent to which they share a common pathogenesis and presentation. Nerve conduction studies in large myelinated fibers have long been the mainstay of preclinical efficacy screening programs and clinical trials, supplemented by quantitative sensory tests. However, a more refined approach is emerging that incorporates measures of small fiber density in the skin and cornea alongside these traditional assays at both preclinical and clinical phases.
Learn More >To investigate whether illness perceptions, measured with the Brief Illness Perception Questionnaire, are an independent predictor of chronic low back pain and pain-related disability at 12 weeks.
Learn More >We tested whether aerobic exercise training altered morphine analgesic responses or reduced morphine dosages necessary for adequate analgesia. Chronic back pain patients were randomized to an 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 45). Before and after the intervention, participants underwent three laboratory sessions (double-blinded, crossover) to assess effects of saline placebo, i.v. morphine (0.09 mg/kg), and i.v. naloxone (12 mg) on low back pain and evoked heat pain responses. Differences in evoked and back pain measures between the placebo and morphine conditions indexed morphine analgesia, with pre-post intervention changes the primary outcome. Endogenous opioid (EO) analgesia was indexed by differences in evoked and low back pain measures between the naloxone and placebo conditions. A Sex X Intervention interaction on the analgesic effects of morphine on VAS back pain intensity was observed (p = .046), with a similar trend for evoked pain threshold (p = .093). Male exercisers showed reduced morphine analgesia pre-post intervention whereas male controls showed increased analgesia (with no differences in females). Of clinical significance were findings that relative to the control group, aerobic exercise produced analgesia more similar to that observed after receiving ≈7 mg morphine pre-intervention (p's < .045). Greater pre-post intervention increases in EO function (from any source) were significantly associated with larger pre-post intervention decreases in morphine analgesia (p's < .046). The overall pattern of findings suggest that regular aerobic exercise has limited direct effects on morphine responsiveness, reducing morphine analgesia in males only.
Learn More >Conditioned pain modulation (CPM) is a centrally processed measure of the net effect of the descending pain pathway. This comprises both the facilitatory as well as the inhibitory effect. In the past, CPM or similar effects have been previously described using different terminologies such as diffuse noxious inhibitory control (DNIC), heterotopic noxious conditioning stimulation (HNCS) or endogenous analgesia (EA). A variety of patient-related factors such as age, gender, hormones, race, genetic and psychological factors have been thought to influence the CPM paradigms. CPM paradigms have also been associated with a wide range of methodological variables including the mode of application of the 'test' as well as the 'conditioning' stimuli. Despite all these variabilities, CPM seems to reliably lend itself to the pain modulation profile concept and could in future become one of the phenotypic biomarkers for pain and also a guide for mechanism-based treatment in chronic pain. Future research should focus on establishing consistent methodologies for measuring CPM and thereby enhancing the robustness of this emerging biomarker for pain.
Learn More >Brief psychological interventions (BPIs) have demonstrated effectiveness in reducing substance use and related harm. No systematic review has examined their potential to reduce or prevent prescription opioid use or related harm, and/or pain intensity in opioid-using patients with chronic non-cancer pain (CNCP). Recognizing the importance of patient preferences in evidence-based practice, we also sought to assess patient interest in BPIs.
Learn More >In this study of 154 community-dwelling older adults with chronic non-cancer pain, we sought to assess participants' beliefs about pain as well as pain management treatments and determined the influence of those beliefs on participants' willingness to undertake three physician-recommended pain treatments, i.e., a pharmacologic, physical, and psychological therapy.
Learn More >There has been a long-standing debate regarding the role of peripheral afferents in mediating rapid-onset anorexia among other responses elicited by peripheral inflammatory insults. Thus, the current study assessed the sufficiency of peripheral afferents expressing toll-like receptor 4 (TLR4) to the initiation of the anorexia caused by peripheral bacterial lipopolysaccharide (LPS). We generated a Tlr4 null (Tlr4) mouse in which Tlr4 expression is globally disrupted by a loxP-flanked transcription blocking cassette. This novel mouse model allowed us to restore the endogenous TLR4 expression in specific cell types. Using Zp3-Cre and Na1.8-Cre mice, we produced mice that express TLR4 in all cells (Tlr4 X Zp3-Cre) and in peripheral afferents (Tlr4 X Na1.8-Cre), respectively. We validated the Tlr4 mice, which were phenotypically identical to previously reported global TLR4 knock-out mice. Contrary to our expectations, the administration of LPS did not cause rapid-onset anorexia in mice with Na1.8-restricted TLR4. The later result prompted us to identify Tlr4-expressing vagal afferents using hybridization. , we found that Tlr4 mRNA was primarily enriched in vagal Na1.8 afferents located in the jugular ganglion that co-expressed Calcitonin gene-related peptide (CGRP). , the application of LPS to cultured Na1.8-restricted TLR4 afferents was sufficient to stimulate the release and expression of CGRP. In summary, we demonstrated using a new mouse model that vagally-expressed TLR4 is selectively involved in stimulating the release of CGRP, but not in causing anorexia. Using a new transgenic mouse model, our data establish that TLR4 is both sufficient and required for the release of CGRP from a subset of vagal afferents. This finding may be relevant to the understanding of how bacterial infections modulate nerves.
Learn More >Engineered human mini-brains, made possible by knowledge from the convergence of precision microengineering and cell biology, permit systematic studies of complex neurological processes and of pathogenesis beyond what can be done with animal models. By culturing human brain cells with physiological microenvironmental cues, human mini-brain models reconstitute the arrangement of structural tissues and some of the complex biological functions of the human brain. In this Review, we highlight the most significant developments that have led to microphysiological human mini-brain models. We introduce the history of mini-brain development, review methods for creating mini-brain models in static conditions, and discuss relevant state-of-the-art dynamic cell-culture systems. We also review human mini-brain models that reconstruct aspects of major neurological disorders under static or dynamic conditions. Engineered human mini-brains will contribute to advancing the study of the physiology and aetiology of neurological disorders, and to the development of personalized medicines for them.
Learn More >The risk constructs based on psychological risk factors (e.g. pain catastrophizing, PC) and sensitization risk factors (e.g. pressure pain threshold, PPT) are important in research and clinical practice. While most research looks at individual constructs, but doesn't consider how different constructs might interact within the same individual. A cumulative impact evaluation of psychological and sensitization risk factors on pain-related outcomes may help guide us in the risk assessment of patients with pain conditions. The aim of this study is to evaluate the cumulative impact of these psychological PC and sensitization PPT risk factors on pain-related outcomes (activity avoidance, pain severity and disability) considering covariates.
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