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Synthesis of clinical practice guideline recommendations for the primary health care of chronic musculoskeletal pain.

The prevalence of chronic musculoskeletal pain (CMSP) is high and rising. The multidimensional impact of CMSP on individuals necessitates multidisciplinary evidence-based strategies to prevent and manage chronic pain. Primary health care (PHC) is the first point of care in many healthcare systems and evidence implementation at this point is important. We aim to describe the process of development of a comprehensive list of evidence-based recommendations derived from different high-quality clinical practice guidelines (CPGs) to inform the PHC healthcare of adults with CMSP.

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Establishing consensus on key elements and implementation enablers of community-based pain programs to support primary health network decision making: an eDelphi study.

To address the growing burden of chronic pain, there is a need for national scale-up of community-based pain programs. Primary health networks (PHNs) are best placed to support this scale-up as commissioning bodies of health services. The aim of this eDelphi study was to establish expert consensus on best practice key elements of community-based pain programs and enablers important for program implementation and sustainability to support PHN decision making. A panel of experts was invited to complete three online survey rounds as part of a reactive eDelphi approach to provide feedback on the relevance and importance of proposed key elements and implementation enablers of community-based pain programs. Consensus of 70% agreement by experts was required for each survey round for items to remain, with comments from experts considered by the research team to agree on wording changes and the addition of new items. Ten experts (62.5%) completed all three survey rounds. Expert feedback resulted in a list of 18 best practice key elements of community-based pain program design and 14 program implementation enablers. Changes suggested by experts included the moving of items between lists, rephrasing of items and the addition of new items. The eDelphi results will serve as a resource for PHNs considering the commissioning of community-based pain programs and inform future research to assess the suitability and scalability of existing programs.

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The Role of the Locus Coeruleus in Pain and Associated Stress-Related Disorders.

The locus coeruleus (LC)-noradrenergic system is the main source of noradrenaline in the central nervous system and is involved intensively in modulating pain and stress-related disorders (e.g., major depressive disorder and anxiety) and in their comorbidity. However, the mechanisms involving the LC that underlie these effects have not been fully elucidated, in part owing to the technical difficulties inherent in exploring such a tiny nucleus. However, novel research tools are now available that have helped redefine the LC system, moving away from the traditional view of LC as a homogeneous structure that exerts a uniform influence on neural activity. Indeed, innovative techniques such as DREADDs (designer receptors exclusively activated by designer drugs) and optogenetics have demonstrated the functional heterogeneity of LC, and novel magnetic resonance imaging applications combined with pupillometry have opened the way to evaluate LC activity in vivo. This review aims to bring together the data available on the efferent activity of the LC-noradrenergic system in relation to pain and its comorbidity with anxiodepressive disorders. Acute pain triggers a robust LC stress response, producing spinal cord-mediated endogenous analgesia while promoting aversion, vigilance, and threat detection through its ascending efferents. However, this protective biological system fails in chronic pain, and LC activity produces pain facilitation, anxiety, increased aversive memory, and behavioral despair, acting at the medulla, prefrontal cortex, and amygdala levels. Thus, the activation/deactivation of specific LC projections contributes to different behavioral outcomes in the shift from acute to chronic pain.

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Well-described exercises for chronic low back pain in Life Science Literature: A systematic review.

Therapeutic exercise (TE) is recommended in multimodal treatment for patients with non-specific chronic back pain (cLBP).

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Reliability of a self-administrated musculoskeletal questionnaire: The fourth Trøndelag health study.

The reliability of the Nordic Musculoskeletal Questionnaire (NMQ) has not been evaluated in an unselected general population. The aim of this population-based follow-up study was to estimate the reliability between a self-administered NMQ-based questionnaire and a face-to-face interview performed approximately two months later. To interpret the results, we assessed the 1-year prevalence of various pain musculoskeletal pain locations.

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Beating Pain with Psychedelics: Matter over Mind?

Basic pain research has shed light on key cellular and molecular mechanisms underlying nociceptive and phenomenological aspects of pain. Despite these advances, [[we still yearn for] the discovery of novel therapeutic strategies to address the unmet needs of about 70% of chronic neuropathic pain patients whose pain fails to respond to opioids as well as to other conventional analgesic agents. Importantly, a substantial body of clinical observations over the past decade cumulatively suggests that the psychedelic class of drugs may possess heuristic value for understanding and treating chronic pain conditions. The present review presents a theoretical framework for hitherto insufficiently understood neuroscience-based mechanisms of psychedelics' potential analgesic effects. To that end, searches of PubMed-indexed journals were performed using the following Medical Subject Headings' terms: pain, analgesia, inflammatory, brain connectivity, ketamine, psilocybin, functional imaging, and dendrites. Recursive sets of scientific and clinical evidence extracted from this literature review were summarized within the following key areas: (1) studies employing psychedelics for alleviation of physical and emotional pain; (2) potential neuro-restorative effects of psychedelics to remediate the impaired connectivity underlying the dissociation between pain-related conscious states/cognitions and the subcortical activity/function leading to the eventual chronicity through immediate and long-term effects on dentritic plasticity; (3) anti-neuroinflammatory and pro-immunomodulatory actions of psychedelics as the may pertain to the role of these factors in the pathogenesis of neuropathic pain; (4) safety, legal, and ethical consideration inherent in psychedelics' pharmacotherapy. In addition to direct beneficial effects in terms of reduction of pain and suffering, psychedelics' inclusion in the analgesic armamentarium will contribute to deeper and more sophisticated insights not only into pain syndromes but also into frequently comorbid psychiatric condition associated with emotional pain, e.g., depressive and anxiety disorders. Further inquiry is clearly warranted into the above areas that have potential to evolve into further elucidate the mechanisms of chronic pain and affective disorders, and lead to the development of innovative, safe, and more efficacious neurobiologically-based therapeutic approaches.

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Purinergic signaling between neurons and satellite glial cells of mouse dorsal root ganglia modulates neuronal excitability in vivo.

Primary sensory neurons in dorsal root ganglia (DRG) are wrapped by satellite glial cells (SGCs), and neuron-SGC interaction may affect somatosensation, especially nociceptive transmission. P2-purinergic receptors (P2Rs) are key elements in the two-way interactions between DRG neurons and SGCs. However, because the cell types are in such close proximity, conventional approaches such as in vitro culture and electrophysiologic recordings are not adequate to investigate the physiologically relevant responses of these cells at a population level. Here, we performed in vivo calcium imaging to survey the activation of hundreds of DRG neurons in Pirt-GCaMP6s mice and to assess SGC activation in GFAP-GCaMP6s mice in situ. By combining pharmacologic and electrophysiologic techniques, we investigated how ganglionic purinergic signaling initiated by α,β-methyleneadenosine 5'-triphosphate (α,β-MeATP) modulates neuronal activity and excitability at a population level. We found that α,β-MeATP induced robust activation of small neurons-likely nociceptors-through activation of P2X3R. Large neurons, which are likely non-nociceptive, were also activated by α,β-MeATP, but with a delay. Blocking pannexin 1 channels attenuated the late phase response of DRG neurons, indicating that P2R stimulation may subsequently induce paracrine ATP release, which could further activate cells in the ganglion. Moreover, ganglionic α,β-MeATP treatment in vivo sensitized small neurons and enhanced responses of spinal wide-dynamic-range neurons to subsequent C-fiber inputs, suggesting that modulation via ganglionic P2R signaling could significantly affect nociceptive neuron excitability and pain transmission. Therefore, targeting functional P2Rs within ganglia may represent an important new strategy for pain modulation.

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When shared pain is not half the pain: enhanced central nervous system processing and verbal reports of pain in the presence of a solicitous spouse.

The experience of pain and pain behaviors is not only determined by physiological but also psychosocial factors. In this context, the learning history of the individual and specifically operant reinforcement related to spouse responses might play an important role. We investigated the effect of a solicitous and habitually pain-reinforcing spouse for the processing of pain in patients with chronic pain. Using multichannel electroencephalography, pain behaviors, and self-reports of pain, we examined 20 patients with chronic back pain (10 with solicitous and 10 with nonsolicitous spouses) and 10 matched healthy controls. The participants received a series of painful and nonpainful electrical stimuli applied to the site of pain (back) and a control area (finger) in the presence vs absence of the spouse. The global field power of the electroencephalogram with a focus in the frontal region was enhanced in patients with chronic back pain who had a solicitous spouse compared to those with a nonsolicitous spouse and the healthy controls. This was specific for the painful stimulation at the back and occurred only in the presence but not the absence of the spouse. Pain ratings of intensity and unpleasantness were also higher in the patients with solicitous spouses when the spouse was present during painful stimulation. These data suggest that significant other responses indicative of operant reinforcement may have a direct effect on the cerebral processing of pain and related pain perception.

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Immunity and pain in the eye: focus on the ocular surface.

Most ocular diseases are associated with pain. While pain has been generally considered a mere (deleterious) additional symptom, it is now emerging that it is a key modulator of innate/adaptive immunity. Because the cornea receives the highest nerve density of the entire body, it is an ideal site to demonstrate interactions between pain and the immune response. Indeed, most neuropeptides involved in pain generation are also potent regulators of innate and adaptive leukocyte physiology. On the other hand, most inflammatory cells can modulate the generation of ocular pain through release of specific mediators (cytokines, chemokines, growth factors, lipid mediators). This review will discuss the reciprocal role(s) of ocular surface (and specifically: corneal) pain on the immune response of the eye. Finally, we will discuss clinical implications of such reciprocal interactions in the context of highly prevalent corneal diseases.

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Procedure-Related Outcomes Including Readmission Following Spinal Cord Stimulator Implant Procedures: A Retrospective Cohort Study.

Spinal cord stimulation (SCS) has been shown to reduce opioid consumption, reduce pain, improve quality of life compared to conventional therapy, and be more effective than spine reoperation in carefully selected patients. In this study, we evaluate readmissions after SCS implantation procedures, costs, predictors, and etiologies for readmission following implantation procedures.

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