Pain
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Randomized Controlled Trial
Cognitive functional therapy compared with core exercise and manual therapy in patients with chronic low back pain: randomised controlled trial.
Cognitive functional therapy (CFT) is a physiotherapy-led intervention that has evolved from an integration of foundational behavioral psychology and neuroscience within the physiotherapist practice directed at the multidimensional nature of chronic low back pain (CLBP). The current evidence about the comparative effectiveness of CFT for CLBP is still scarce. We aimed to investigate whether CFT is more effective than core training exercise and manual therapy (CORE-MT) in pain and disability in patients with CLBP. ⋯ Cognitive functional therapy was more effective than CORE-MT in disability at 8 weeks (MD = -4.75; 95% CI -8.38 to -1.11; P = 0.011, effect size= 0.55) but not in pain intensity (MD = -0.04; 95% CI -0.79 to 0.71; P = 0.916). Treatment with CFT reduced disability, but the difference was not clinically important compared with CORE-MT postintervention (short term) in patients with CLBP. There was no difference in pain intensity between interventions, and the treatment effect was not maintained in the mid-term and long-term follow-ups.
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Ample data support a prominent role of peripheral T-type calcium channels 3.2 (Ca V 3.2) in generating pain states. Development of primary sensory neuron-specific inhibitors of Ca V 3.2 channels is an opportunity for achieving effective analgesic therapeutics, but success has been elusive. Small peptides, especially those derived from natural proteins as inhibitory peptide aptamers (iPAs), can produce highly effective and selective blockade of specific nociceptive molecular pathways to reduce pain with minimal off-target effects. ⋯ Two prototype Ca V 3.2iPAs (iPA1 and iPA2) derived from the IDRs of Ca V 3.2 intracellular loops 2 and 3, respectively, were expressed selectively in the primary sensory neurons of dorsal root ganglia in vivo using recombinant adeno-associated virus (AAV), which produced sustained inhibition of calcium current conducted by Ca V 3.2/T-type channels and significantly attenuated both evoked and spontaneous pain behavior in rats with neuropathic pain after tibial nerve injury. Recordings from dissociated sensory neurons showed that AAV-mediated Ca V 3.2iPA expression suppressed neuronal excitability, suggesting that Ca V 3.2iPA treatment attenuated pain by reversal of injury-induced neuronal hypersensitivity. Collectively, our results indicate that Ca V 3.2iPAs are promising analgesic leads that, combined with AAV-mediated delivery in anatomically targeted sensory ganglia, have the potential to be a selective peripheral Ca V 3.2-targeting strategy for clinical treatment of pain.
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Observational Study
Post-acute sensory neurological sequelae in patients with SARS-CoV-2 infection: the COVID-PN observational cohort study.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause neurological sequelae after the resolution of symptomatic COVID-19 illness, but the occurrence of peripheral neuropathy symptoms and cranial nerve dysfunction is unknown. This study aimed to characterize the occurrence and severity of pain and peripheral neuropathy symptoms in patients with SARS-CoV-2 infection. An observational cohort study included adults tested for a SARS-CoV-2 infection at an academic medical center (assigned as CV+ or control, based on test results). ⋯ The occurrence of pain in the extremities was higher in the CV+ group (24.2% vs 9.8%, OR = 2.95 [2.21-3.91]). SARS-CoV-2 infection was also associated with higher occurrence of peripheral neuropathy symptoms, after adjusting for the history of chronic pain and neuropathy (OR = 3.19 [2.37-4.29]). The results suggest that SARS-CoV-2 infection was independently associated with an increased risk of pain and peripheral neuropathy symptoms.
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Response to analgesic therapy is influenced by several factors including genetics and drug-drug interactions. Pharmacogenetic (PGx) variants in the CYP2D6 gene modify response to opioids by altering drug metabolism. We sought to determine the potential impact of PGx testing on the care of Veterans with noncancer pain prescribed opioids metabolized by CYP2D6 (codeine, hydrocodone, or tramadol). ⋯ An estimated 21.6% (n = 526,905) of these patients are at an elevated risk of an undesirable response to their opioid medication based on predicted phenotypes and drug-drug interactions: 3.5% are predicted CYP2D6 ultrarapid metabolizers and at increased risk for toxicity, 5.4% are poor metabolizers at higher risk for nonresponse, and 12.8% are normal or intermediate metabolizers coprescribed a CYP2D6 inhibitor leading to phenoconversion into poor metabolizer. Despite the high rate of coprescription of opioids and interacting drugs, CYP2D6 testing was infrequent in the sample (0.02%), and chart review suggests that test results were used to optimize antidepressant treatments rather than pain medications. Using PGx testing combined with consideration of phenoconversion may allow for an enhanced precision medicine approach to pain management in Veterans.