The journal of pain : official journal of the American Pain Society
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Despite promising preliminary results in treating fibromyalgia (FM) pain, no neuromodulation technique has been adopted in clinical practice because of limited efficacy, low response rate, or poor tolerability. This phase II open-label trial aims to define a methodology for a clinically effective treatment of pain in FM by establishing treatment protocols and screening procedures to maximize efficacy and response rate. High-definition transcranial direct current stimulation (HD-tDCS) provides targeted subthreshold brain stimulation, combining tolerability with specificity. We aimed to establish the number of HD-tDCS sessions required to achieve a 50% FM pain reduction, and to characterize the biometrics of the response, including brain network activation pain scores of contact heat-evoked potentials. We report a clinically significant benefit of a 50% pain reduction in half (n = 7) of the patients (N = 14), with responders and nonresponders alike benefiting from a cumulative effect of treatment, reflected in significant pain reduction (P = .035) as well as improved quality of life (P = .001) over time. We also report an aggregate 6-week response rate of 50% of patients and estimate 15 as the median number of HD-tDCS sessions to reach clinically meaningful outcomes. The methodology for a pivotal FM neuromodulation clinical trial with individualized treatment is thus supported. ⋯ In this article, an optimized protocol for the treatment of fibromyalgia pain with targeted subthreshold brain stimulation using high-definition transcranial direct current stimulation is outlined.
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It has long been known that the bedding type on which animals are housed can affect breeding behavior and cage environment, yet little is known about its effects on evoked behavior responses or nonreflexive behaviors. C57BL/6 mice were housed for 2 weeks on 1 of 5 bedding types: aspen Sani-Chips (standard bedding for our institute), ALPHA-Dri, Cellu-Dri, Pure-o'Cel, or TEK-Fresh. Mice housed on aspen exhibited the lowest (most sensitive) mechanical thresholds and those on TEK-Fresh exhibited 3-fold higher thresholds. Although bedding type had no effect on responses to punctate or dynamic light touch stimuli, TEK-Fresh-housed animals exhibited greater responsiveness in a noxious needle assay than did those housed on the other bedding types. Heat sensitivity was also affected by bedding because animals housed on aspen exhibited the shortest (most sensitive) latencies to withdrawal, whereas those housed on TEK-Fresh had the longest (least sensitive) latencies to response. Slight differences between bedding types were also seen in a moderate cold temperature preference assay. A modified tactile conditioned place preference chamber assay revealed that animals preferred TEK-Fresh to aspen bedding. Bedding type had no effect in a nonreflexive wheel running assay. In both acute (2 day) and chronic (5 week) inflammation induced by injection of complete Freund's adjuvant in the hindpaw, mechanical thresholds were reduced in all groups regardless of bedding type, but TEK-Fresh and Pure-o'Cel groups exhibited a greater dynamic range between controls and inflamed cohorts than aspen-housed mice. ⋯ These findings indicate that the bedding type routinely used to house animals can markedly affect the dynamic range of mechanical and heat behavior assays under normal and tissue injury conditions. Among beddings tested, TEK-Fresh bedding resulted in the least sensitive baseline thresholds for mechanical and thermal stimuli and the greatest dynamic range after tissue injury. Therefore, selection of routine cage bedding material should be carefully considered for animals that will be tested in behavioral somatosensory assays.