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Adults with chronic low back pain, disability, moderate to severe pain, and high fear of movement and re-injury were recruited into a trial of a novel, automated, digital therapeutics, virtual reality, psychological intervention for pain (DTxP). We conducted a three-arm, prospective, double-blind, pilot, randomized controlled trial comparing DTxP with a sham placebo comparator, and an open label standard care. Participants were enrolled for 6-8 weeks, after which, the standard care control arm were re-randomized to receive either the DTxP or sham placebo. Forty-two participants completed assessments at baseline, immediately post-treatment (6-8 weeks), 9-week, and 5-month follow-up. We found participants in the DTxP group reported greater reductions in fear of movement and better global impression of change when compared with sham placebo and standard care post-treatment. No other group differences were noted at post-treatment or follow-up. When compared to baseline, participants in the DTxP group reported lower disability at 5-month follow-up, lower pain interference and fear of movement post-treatment and follow-up, and lower pain intensity at post-treatment. The sham placebo group also reported lower disability and fear of movement at 5-month follow-up compared to baseline. Standard care did not report any significant changes. There were a number of adverse events, with one participant reporting a serious adverse event in the sham placebo which was not related to treatment. No substantial changes in medications were noted, and participants in the DTxP group reported positive gaming experiences.
Learn More >The main aim of this systematic review and meta-analysis (MA) was to assess the effectiveness of online behavior modification techniques (e-BMT) in the management of chronic musculoskeletal pain.
Learn More >Transcranial focused ultrasound (tFUS) is regarded as a promising non-invasive stimulation tool for modulating brain circuits. The aim of this study is to explore the feasibility of tFUS stimulation for analgesia application.
Learn More >To evaluate the impact of virtual reality on pain management during normal labor.
Learn More >Trafficking and activation of N-methyl-D-aspartate (NMDA) receptors play an important role in initiating and maintaining postoperative remifentanil-induced hyperalgesia (RIH). Activation of the NOD-like receptor protein 3 (NLRP3) inflammasome has been linked to the development of inflammatory and neuropathic pain. We hypothesized that activation of NLRP3 inflammasome mediates IL-1β release and contributes to RIH in rats by increasing NMDA receptor NR1 (NR1) subunit phosphorylation and decreasing glutamate transporter-1 (GLT-1) expression.
Learn More >Resistance training-based exercise is commonly prescribed in the clinic for the treatment of chronic pain. Mechanisms of aerobic exercise for analgesia are frequently studied, while little is known regarding resistance training mechanisms. We developed a resistance training model in mice and hypothesized resistance training would protect against development of muscle pain, mediated through the activation of androgen receptors. Activity induced muscle hyperalgesia was produced by two injections of pH 5.0 stimuli with fatiguing muscle contractions. Resistance training was performed by having mice climb a ladder with attached weights, 3x per week. Resistance training acutely increased blood lactate and prolonged training increased strength measured via forepaw grip strength and 1 repetition maximum, validating the exercise program as a resistance training model. Eight weeks of resistance training prior to induction of the pain model blocked the development of muscle hyperalgesia in both sexes. Resistance training initiated after induction of the pain model reversed muscle hyperalgesia in males only. A single resistance training bout acutely increased testosterone in male but not female mice. Administration of the androgen receptor antagonist flutamide (200mg pellets) throughout the eight-week training program blocked the exercise induced protection against muscle pain in both sexes. However, single administration of flutamide (1, 3, 10mg/kg) in resistance trained animals had no effect on existing exercise induced protection against muscle pain. Therefore, resistance training acutely increases lactate and testosterone and strength overtime. Eight weeks of resistance training prevents development of hyperalgesia through activation of androgen receptors in an animal model of muscle pain.
Learn More >Pain-related avoidance of movements that are actually safe (i.e., overprotective behavior) plays a key role in chronic pain disability. Avoidance is reinforced through operant learning: after learning that a certain movement elicits pain, movements that prevent pain are more likely to be performed. Proprioceptive accuracy importantly contributes to motor learning and memory. Interestingly, reduced accuracy has been documented in various chronic pain conditions, prompting the question whether this relates to avoidance becoming excessive. Using robotic arm-reaching movements, we tested the hypothesis that poor proprioceptive accuracy is associated with excessive pain-related avoidance in pain-free participants. Participants first performed a task to assess proprioceptive accuracy, followed by an operant avoidance training during which a pain stimulus was presented when they performed one movement trajectory, but not when they performed another trajectory. During a test phase, movements were no longer restricted to two trajectories, but participants were instructed to avoid pain. Unbeknownst to the participants, the pain stimulus was never presented during this phase. Results supported our hypothesis. Furthermore, exploratory analyses indicated a reduction in proprioceptive accuracy after avoidance learning, which was associated with excessive avoidance and higher trait fear of pain. Perspective: This study is the first to show that poorer proprioceptive accuracy is associated with excessive pain-related avoidance. This finding is especially relevant for chronic pain conditions, as reduced accuracy has been documented in these populations, and points toward the need for research on training accuracy to tackle excessive avoidance.
Learn More >Inclinicalpractice, high-voltage, long-duration pulsed radiofrequency (HL-PRF) is effective for several types of intractable neuropathic pain (NP), but the mechanisms have not been well explored. Cav2.2 channels could increase neuronal excitability and neurotransmission accompanying NP. This study investigated the relationship of the efficacy of HL-PRF on NP with the levels of Cav2.2 in the spinal dorsal horn (SDH) and dorsal root ganglions (DRGs) of chronic constriction injury (CCI) in rats. Sham HL-PRF, GVIA (a specific Cav2.2 channel blocker), HL-PRF, or GVIA + HL-PRF was applied to CCI rats. The results showed: compared with the sham group, the PWT and PWL of CCI rats decreased significantly (P < 0.05), and Cav2.2 expression was elevated significantly in the SDH and DRGs (P < 0.05). Compared with the CCI group, both HL-PRF and ω-conotoxin GVIA treatment reversed the increased PWT and PWL (P < 0.05) and downregulated the overexpression of Cav2.2 in the SDH and DRGs (P < 0.05). Furthermore, PWT, PWL, and the expression of Cav2.2 in the SDH and DRGs were not significantly different among the 3 treatment groups. HL-PRF on L DRG reversed the hyperalgesia behavior of NP and reduced the levels of Cav2.2 in the ipsilateral SDH and DRGs in CCI rats. Moreover, the underlying mechanism may be related to the downregulation of CaV2.2 protein levels in both SDH and DRG.
Learn More >NO, or nitric oxide, is produced by a family of enzymes called nitric oxide synthase (NOS) from L-arginine. NO regulates many physiological functions such as smooth muscle relaxation, immune defense, and memory function. The overproduction of NO by the neuronal isoform of nitric oxide synthase (nNOS) is implicated in neurodegeneration and neuropathic pain, making nNOS inhibition a promising therapeutic approach. Many developed nNOS inhibitors, generally L-arginine mimetics, have some issues in selectivity and bioavailability. According to earlier studies, targeting nNOS has the advantage of decreasing excess NO in the brain while avoiding the negative consequences of inhibiting the two isozymes: endothelial NOS (eNOS) and inducible NOS (iNOS). This study applied structure-based virtual screening, molecular docking, and molecular dynamics simulations to design potent and selective inhibitors against nNOS over related isoforms (eNOS and iNOS) using human X-ray crystal structures of the NOS isoforms. It was discovered that some compounds displayed a very good inhibitory potency for hnNOS and moderate selectivity for the other isozymes, eNOS and iNOS, in addition to good solubility and desirable physiochemical properties. The compounds which showed good stability and selectivity with nNOS, such as ZINC000013485422, can be interesting and informative guidance for designing more potent human nNOS inhibitors.Communicated by Ramaswamy H. Sarma.
Learn More >Experimental pain during gait has been shown to interfere with learning a new locomotor task. However, very few studies have investigated the impact of clinical pain on motor learning due to the challenges associated with clinical populations.
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