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There is evidence that people with persistent shoulder pain exhibit findings consistent with the presence of sensorimotor dysfunction. Sensorimotor impairments can manifest in a variety of ways, and further developing our understanding of sensorimotor dysfunction in shoulder pain may improve current models of care. The Fremantle Back Awareness Questionnaire (FreBAQ) has been developed to assess disturbed body perception specific to the back. The purpose of the present study was to develop a shoulder-specific self-perception questionnaire and evaluate the questionnaire in people with persistent shoulder pain.
Learn More >Nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) are essential for neuronal development and survival in embryo. However, after birth they play pivotal roles in generation of hyperalgesia in many painful conditions. Both factors are believed to act on different groups of primary afferents, and no interaction has been studied. Here we show a synergism of both factors. Intramuscular injection of a mixture of both factors of low concentration, each of which alone had no effect, induced a significant muscular mechanical hyperalgesia in rats. We show synergism occurs in the primary afferent neurons and find about 25 % primary afferents innervating the muscle express both TrkA (NGF receptor) and GFRα1 (GDNF receptor). We show by pharmacological means that afferent neurons with TrkA and GFRα1 express both TRPV1 and ASICs. Our data establish a basis for synergism of NGF and GDNF.
Learn More >Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) are common drug targets and canonically couple to specific G protein subtypes and β-arrestin adaptor proteins. G protein- and β-arrestin-mediated signaling have been considered separable. We show GPCRs promote a direct interaction between G protein subtype family members and β-arrestins, regardless of their canonical G protein subtype coupling. G:β-arrestin complexes bound extracellular signal-regulated kinase (ERK) and their disruption impaired both ERK activation and cell migration, consistent with β-arrestins requiring a functional interaction with G for certain signaling events. These results introduce a GPCR signaling mechanism distinct from canonical G protein activation in which GPCRs cause the formation of G:β-arrestin signaling complexes.
Learn More >The aim of the present study was to investigate the analgesic effects of repetitive transcranial magnetic stimulation over the primary motor cortex (M1-rTMS) using different stimulation parameters to explore the optimal stimulus condition for treating neuropathic pain.
Learn More >Although evidence-based psychological treatments for chronic pain have been demonstrated to be effective for a variety of outcomes, modest effects observed in recent reviews indicate scope for improvement. Self-compassion promotes a proactive attitude towards self-care and actively seeking relief from suffering. Consequently, more compassionate people experience better physical, psychological, and interpersonal wellbeing.
Learn More >Studies have reported relief of chronic shoulder pain with non-ablative pulsed neuromodulatory [pRF] or ablative radiofrequency [aRF] procedures on innervation of the shoulder joint but interpretation of these reports is hampered by inconsistent indications, anatomic targets, and follow-up. This systematic review was conducted to synthesize the existing literature on procedures employing pRF or aRF for treating chronic shoulder pain.
Learn More >We investigated patients with chronic pain seeking medical cannabis. We assessed their demographics, patterns of cannabis use, and the long-term effectiveness of cannabis on their pain and functional domains.
Learn More >This study examined the prevalence of chronic pain alone, posttraumatic stress disorder (PTSD) alone, and both chronic pain and PTSD among U.S. Army soldiers during the postdeployment year.
Learn More >The three peripheral sensory neuron (SN) subtypes, nociceptors, mechanoreceptors, and proprioceptors, localize to dorsal root ganglia and convey sensations such as pain, temperature, pressure, and limb movement/position. Despite previous reports, to date no protocol is available allowing the generation of all three SN subtypes at high efficiency and purity from human pluripotent stem cells (hPSCs). We describe a chemically defined differentiation protocol that generates all three SN subtypes from the same starting population, as well as methods to enrich for each individual subtype. The protocol yields high efficiency and purity cultures that are electrically active and respond to specific stimuli. We describe their molecular character and maturity stage and provide evidence for their use as an axotomy model; we show disease phenotypes in hPSCs derived from patients with familial dysautonomia. Our protocol will allow the modeling of human disorders affecting SNs, the search for treatments, and the study of human development.
Learn More >After surgery, acute pain is still managed insufficiently and may lead to short- and long-term complications including chronic postsurgical pain and an increased prescription of opioids. Thus, identifying new targets specifically implicated in postoperative pain is of utmost importance to develop effective and non-addictive analgesics. Here, we employed an integrated and multimethod workflow to reveal unprecedented insights into proteome dynamics in dorsal root ganglia (DRG) of mice after plantar incision (INC). Based on a detailed characterization of INC-associated pain-related behavior profiles, including a novel paradigm for non-evoked pain (NEP), we performed quantitative mass-spectrometry-based proteomics in DRG 1 day after INC. Our data revealed a hitherto unknown INC-regulated protein signature in DRG with changes in distinct proteins and cellular signaling pathways. In particular, we show the differential regulation of 44 protein candidates, many of which are annotated with pathways related to immune and inflammatory responses such as MAPK/ERK signaling. Subsequent orthogonal assays comprised multiplex western blotting, bioinformatic protein network analysis, and immunolabeling in independent mouse cohorts to validate (i) the INC-induced regulation of immune/inflammatory pathways and (ii) the high priority candidate Annexin A1 (Anxa1). Taken together, our results propose novel potential targets in the context of incision and, therefore, represent a highly valuable resource for further mechanistic and translational studies of postoperative pain.
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