Pain
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We describe here the development and validation of the Osteoarthritis Symptom Inventory Scale (OASIS), a new self-administered questionnaire specifically designed to evaluate the various osteoarthritis (OA) pain symptoms with different dimensions related to OA pain mechanisms. The initial development phase and qualitative study generated a list of 17 descriptors reflecting OA pain and other associated symptoms, leading to the first version of the questionnaire (OASIS17). Each item was quantified on a 0 to 10 Numerical Scale. ⋯ The final OASIS version includes 9 items discriminating and quantifying 3 distinct, clinically relevant OA pain dimensions sensitive to treatment. OASIS9 psychometric properties suggest that it could improve the characterization of OA pain profiles for 3 clinically relevant domains: localized, neuropathic-like, and deep pain. The OASIS9 questionnaire could be used to phenotype OA pain patients and identify responders to various therapeutic interventions as a function of OA pain dimensions.
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Mounting evidence indicates that microRNAs (miRNAs) play critical roles in various pathophysiological conditions and diseases, but the physiological roles of extracellular miRNAs on the disease-related ion channels remain largely unknown. Here, we showed that miR-1306-3p evoked action potentials and induced inward currents of the acutely isolated rat dorsal root ganglion (DRG) neurons. The miR-1306-3p-induced effects were significantly inhibited by A317491, a potent inhibitor of the P2X3 receptor (P2X3R), or disappeared after the knockdown of P2X3Rs in DRG neurons. ⋯ Intrathecal injection of miR-1306-3p produced visceral pain but not somatic pain in normal control rats. Conversely, intrathecal application of a miR-1306-3p antagomir and A317491 significantly alleviated visceral pain in a rat model of chronic visceral pain. Together, our findings suggest that miR-1306-3p might function as an endogenous ligand to activate P2X3Rs, eventually leading to chronic visceral pain.
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Chronic pain is a significant health problem associated with disability and reduced quality of life. Current management of chronic pain is inadequate with only modest effects of pharmacological interventions. Thus, there is a need for the generation of analgesics for treating chronic pain. ⋯ Sustained release of SARM, from the microparticle formulation, was observed both in vitro and in vivo for 4 weeks. Selective androgen receptor modulator treatment produced no cardiac or liver toxicity and did not produce rewarding behaviors. These studies demonstrate that SARM-loaded microparticles, which release drug for a sustained period, alleviate muscle pain, are safe, and may serve as a potential therapeutic for chronic muscle pain.
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Targeting the vascular endothelial growth factor A/neuropilin 1 axis for relief of neuropathic pain.
Vascular endothelial growth factor A (VEGF-A) is a pronociceptive factor that causes neuronal sensitization and pain. We reported that blocking the interaction between the membrane receptor neuropilin 1 (NRP1) and VEGF-A-blocked VEGF-A-mediated sensory neuron hyperexcitability and reduced mechanical hypersensitivity in a rodent chronic neuropathic pain model. These findings identified the NRP1-VEGF-A signaling axis for therapeutic targeting of chronic pain. ⋯ In rats with spared nerve injury-induced neuropathic pain, intrathecal administration of NRP1-4 significantly attenuated mechanical allodynia. Intravenous treatment with NRP1-4 reversed both mechanical allodynia and thermal hyperalgesia in rats with L5/L6 spinal nerve ligation-induced neuropathic pain. Collectively, our findings show that NRP1-4 is a first-in-class compound targeting the NRP1-VEGF-A signaling axis to control voltage-gated ion channel function, neuronal excitability, and synaptic activity that curb chronic pain.
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Identifying nonspecific low back pain (LBP) in medico-administrative databases is a major challenge because of the number and heterogeneity of existing diagnostic codes and the absence of standard definitions to use as reference. The objective of this study was to evaluate the sensitivity and specificity of algorithms for the identification of nonspecific LBP from medico-administrative data using self-report information as the reference standard. Self-report data came from the PROspective Québec Study on Work and Health , a 24-year prospective cohort study of white-collar workers. ⋯ An algorithm that included at least 1 diagnostic code for nonspecific LBP was best to identify cases of LBP in medico-administrative data with sensitivity varying between 8.9% (95% confidence interval [CI] 7.9-10.0) for a 1-year window and 21.5% (95% CI 20.0-23.0) for a 3-year window. Specificity varied from 97.1% (95% CI 96.5-97.7) for a 1-year window to 90.4% (95% CI 89.4-91.5) for a 3-year window. The low sensitivity we found reveals that the identification of nonspecific cases of LBP in administrative data is limited, possibly due to the lack of traditional medical consultation.