Pain
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Targeting proteins within the N-type voltage-gated calcium channel (CaV2.2) complex has proven to be an effective strategy for developing novel pain therapeutics. We describe a novel peptide aptamer derived from the collapsin response mediator protein 2 (CRMP2), a CaV2.2-regulatory protein. Addition of a 14-carbon myristate group to the peptide (myr-tat-CBD3) tethered it to the membrane of primary sensory neurons near surface CaV2.2. ⋯ Myr-tat-CBD3 was effective in significantly attenuating carrageenan-induced thermal hypersensitivity and reversing thermal hypersensitivity induced by a surgical incision of the plantar surface of the rat hind paw, a model of postoperative pain. These effects are compared with those of tat-CBD3-the nonmyristoylated tat-conjugated CRMP2 peptide as well as scrambled versions of CBD3 and CBD3-lacking control peptides. Our results demonstrate that the myristoyl tag enhances intracellular delivery and local concentration of the CRMP2 peptide aptamer near membrane-delimited calcium channels resulting in pronounced interference with the calcium channel complex, superior suppression of calcium influx, and better antinociceptive potential.
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Randomized Controlled Trial
Cerebral analgesic response to non-steroidal anti-inflammatory drug ibuprofen.
Nonopioid agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the antihyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in presurgical and postsurgical states and looked at the analgesic interaction between surgical state and treatment. ⋯ However, in the postsurgical state, we observed increased activation of top-down modulatory circuits, which was accompanied by decreases in the areas engaged because of ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management.
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Review Meta Analysis
THE PERIOPERATIVE USE OF PREGABALIN FOR ACUTE PAIN- A SYSTEMATIC REVIEW AND META- ANALYSIS.
Evidence supporting postoperative pain management using pregabalin as an adjunct intervention across various surgical pain models is lacking. The objective of this systematic review was to evaluate "model-specific" comparative effectiveness and harms of pregabalin following a previously published systematic review protocol. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through August 2013. ⋯ Pregabalin analgesic effectiveness is largely restricted to surgical procedures associated with pronociceptive mechanisms. The clinical significance of observed pregabalin benefits must be weighed against the uncertainties about serious harms and enhanced recovery to inform the careful selection of surgical patients. Recommendations for future research are proposed.
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Placebo and nocebo play an important role in clinical practice and medical research. Modulating placebo/nocebo responses using noninvasive brain stimulation methods, such as transcranial direct current stimulation (tDCS), has the potential to harness these effects to therapeutic benefit in a clinical setting. In this study, we assessed the effect of anodal and cathodal tDCS over the right dorsolateral prefrontal cortex (rDLPFC) on conditioned placebo/nocebo cue response to heat pain. ⋯ The duration of cue presentation varied to allow either fully conscious or subliminal processing. Significant placebo and nocebo effects in the anodal but not the cathodal group were elicited with the conditioning paradigm. This study provides evidence of a possibility to modulate the conditioned placebo and nocebo effect by changing the excitability of the rDLPFC using tDCS.