Articles: neuralgia.
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Randomized Controlled Trial Multicenter Study
Perioperative Pregabalin and Intraoperative Lidocaine Infusion to Reduce Persistent Neuropathic Pain After Breast Cancer Surgery: A Multicenter, Factorial, Randomized, Controlled Pilot Trial.
Persistent postsurgical pain is defined as pain localized to the area of surgery of a duration of ≥2 months and is, unfortunately, a common complication after breast cancer surgery. Although there is insufficient evidence to support any preventative strategy, prior literature suggests the possible efficacy of intravenous lidocaine and perioperative pregabalin in preventing persistent pain after surgery. To determine feasibility of conducting a larger definitive trial, we conducted a multicenter 2 × 2 factorial, randomized, placebo-controlled pilot trial of 100 female patients undergoing breast cancer surgery. ⋯ Our pilot trial successfully demonstrated feasibility and provided promising data for conducting further trials of intraoperative lidocaine infusions during breast cancer surgeries. Clinical trial number: NCT02240199 PERSPECTIVE: This article reports the findings of a pilot randomized, controlled trial evaluating the effects of perioperative pregabalin and intraoperative lidocaine infusions in patients undergoing breast cancer surgery. This trial demonstrated the feasibility of conducting a larger trial and provided promising data that these interventions may decrease the development of persistent pain.
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Anesthesia and analgesia · Aug 2019
Inhibition of Fatty Acid Amide Hydrolase Improves Depressive-Like Behaviors Independent of Its Peripheral Antinociceptive Effects in a Rat Model of Neuropathic Pain.
Neuropathic pain is often associated with depression. Enhancing endocannabinoids by fatty acid amide hydrolase (FAAH) inhibitors relieves neuropathic pain and stress-induced depressive-like behaviors in animal models. However, it is unclear whether FAAH inhibitor can relieve neuropathic pain-induced depression by or not by its antinociceptive effects. ⋯ Inhibition of FAAH can improve depressive-like behaviors induced by neuropathic pain independent of its peripheral antinociceptive action. Enhanced neurogenesis in hippocampus might contribute to the antidepressive effects of URB597.
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Anesthesia and analgesia · Aug 2019
Spinal Activation of Tropomyosin Receptor Kinase-B Recovers the Impaired Endogenous Analgesia in Neuropathic Pain Rats.
Although endogenous analgesia plays an important role in controlling pain states, chronic pain patients exhibit decreased endogenous analgesia compared to healthy individuals. In rats, noxious stimulus-induced analgesia (NSIA), which is an indicator of endogenous analgesia, diminished 6 weeks after spinal nerve ligation (SNL6W). A recent study in rats with deleted noradrenergic fibers demonstrated that the noradrenergic fibers were essential to NSIA. It has also been reported that brain-derived neurotrophic factor increased spinal noradrenergic fibers. Therefore, this study examined the effect of TrkB activation, which is the receptor for brain-derived neurotrophic factor, on impaired NSIA in SNL6W rats. In addition, we also examined the effect of endogenous analgesia on acute incisional pain. ⋯ Spinal activation of TrkB may recover the attenuated endogenous analgesia by improving the adrenergic plasticity, thereby leading to prevention of pain prolongation after surgery.
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Transmission of pain signals from primary sensory neurons to secondary neurons of the central nervous system is critically dependent on presynaptic voltage-gated calcium channels. Calcium channel-binding domain 3 (CBD3), derived from the collapsin response mediator protein 2 (CRMP2), is a peptide aptamer that is effective in blocking N-type voltage-gated calcium channel (CaV2.2) activity. We previously reported that recombinant adeno-associated virus (AAV)-mediated restricted expression of CBD3 affixed to enhanced green fluorescent protein (EGFP) in primary sensory neurons prevents the development of cutaneous mechanical hypersensitivity in a rat neuropathic pain model. ⋯ We additionally observed that the increased CaV2.2α1b immunoreactivity in the ipsilateral spinal cord dorsal horn and DRG following TNI was significantly normalized by AAV6-CBD3A6K treatment. Finally, the increased neuronal activity in the ipsilateral dorsal horn that developed after TNI was reduced by AAV6-CBD3A6K treatment. Collectively, these results indicate that DRG-restricted AAV6 delivery of CBD3A6K is an effective analgesic molecular strategy for the treatment of established neuropathic pain.
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Data from preclinical research have been suggested to suffer from a lack of inherent reproducibility across laboratories. The goal of our study was to replicate findings from a previous report that demonstrated positive effects of Meteorin, a novel neurotrophic factor, in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Notably, 5 to 6 intermittent subcutaneous (s.c.) injections of Meteorin had been reported to produce reversal of mechanical allodynia/thermal hyperalgesia after injury, wherein maximum efficacy of Meteorin was reached slowly and outlasted the elimination of the compound from the blood by several weeks. ⋯ Systemic administration of recombinant mouse Meteorin (0.5 and 1.8 mg/kg, s.c.) at days 10, 12, 14, 17, and 19 after CCI produced a prolonged reversal of neuropathic hypersensitivity with efficacy comparable with that obtained with gabapentin (100 mg/kg, orally). Despite some protocol deviations (eg, nociceptive endpoint, animal vendor, testing laboratory, investigator, etc.) being incurred, these did not affect study outcome. By paying careful attention to key facets of study design, using bioactive material, and confirming drug exposure, the current data have replicated the salient findings of the previous study, promoting confidence in further advancement of this novel molecule as a potential therapy for neuropathic pain.