Pain
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Proof-of-concept (POC) clinical trials play an important role in developing novel treatments and determining whether existing treatments may be efficacious in broader populations of patients. The goal of most POC trials is to determine whether a treatment is likely to be efficacious for a given indication and thus whether it is worth investing the financial resources and participant exposure necessary for a confirmatory trial of that intervention. A challenge in designing POC trials is obtaining sufficient information to make this important go/no-go decision in a cost-effective manner. ⋯ The trade-off between parallel-group and crossover designs with respect to overall sample sizes, trial duration, and applicability is summarized. The advantages and disadvantages of more recent trial designs, including N-of-1 designs, enriched designs, adaptive designs, and sequential parallel comparison designs, are summarized, and recommendations for consideration are provided. More attention to identifying efficient yet powerful designs for POC clinical trials of chronic pain treatments may increase the percentage of truly efficacious pain treatments that are advanced to confirmatory trials while decreasing the percentage of ineffective treatments that continue to be evaluated rather than abandoned.
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Multicenter Study
Pain Location and Duration Impact Life Function Interference During the Year Following Motor Vehicle Collision.
Persistent musculoskeletal pain is common after motor vehicle collision (MVC) and often results in substantial disability. The objective of this study was to identify distributions of post-MVC pain that most interfere with specific life functions and that have the greatest interference with aggregate life function. Study data were obtained from a prospective longitudinal multicenter emergency department-based cohort of 948 European Americans experiencing MVC. ⋯ Moderate or severe low back pain was as common as neck pain at week 6 (prevalence 37% for each) and overlapped with neck pain in only 23% of patients. Further, pain across all body regions accounted for nearly twice as much of the variance in pain interference as neck pain alone (60% vs 34%). These findings suggest that studies of post-MVC pain should not focus on neck pain alone.
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Testicular pain syndrome (TPS), defined as an intermittent or constant pain in one or both testicles for at least 3 months, resulting in significant reduction of daily activities, is common. Microsurgical denervation of the spermatic cord (MDSC) has been suggested as an effective treatment option. The study population comprised 180 TPS patients admitted to our outpatient urology clinic between 1999 and 2011. ⋯ At mean follow-up of 42.8 months, 86.2% had a ≥ 50% reduction of pain and 51.7% were completely pain free. MDSC is a valuable treatment option for TPS patients because in this study 86.2% experienced a ≥ 50% reduction of pain. To prevent superfluous diagnostics and treatment, it is mandatory to follow a systematic protocol in the treatment of TPS.
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Itch is a common experience. It can occur in the course of systemic diseases and can be a manifestation of allergies or a consequence of diseases affecting the somatosensory pathway. We describe a kindred characterized by paroxysmal itch caused by a variant in SCN9A gene encoding for the Nav1.7 sodium channel. ⋯ All affected members harbored the 2215A>G I739V substitution in exon 13 of SCN9A gene. Pregabalin treatment reduced itch intensity and attack frequency in all patients. The co-segregation of the I739V variant in the affected members of the family provides evidence, for the first time, that paroxysmal itch can be related to a mutation in sodium channel gene.
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The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear, and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-sex matched control subjects before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared with control subjects, with differences predominantly in the left amygdala in the pretreated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy control subjects from time 1 to time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores; and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity after an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response.