Pain
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Randomized Controlled Trial
Extended-release gabapentin for failed back surgery syndrome: results from a randomized double-blind cross-over study.
Extended-release gabapentin does not improve persistent pain after unsuccessful lumbar spine surgery.
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Randomized Controlled Trial Multicenter Study
Mirogabalin for the management of postherpetic neuralgia: a randomized, double-blind, placebo-controlled phase 3 study in Asian patients.
This study investigated the safety and efficacy of mirogabalin, a novel, potent, selective ligand of the α2δ subunit of voltage-dependent Ca channels, for the treatment of postherpetic neuralgia (PHN). In this multicenter, double-blind, placebo-controlled phase 3 study, Asian patients ≥20 years with PHN were randomized 2:1:1:1 to placebo or mirogabalin 15, 20, or 30 mg/day for up to 14 weeks (NCT02318719). The primary efficacy endpoint was the change from baseline in average daily pain score at week 14, defined as a weekly average of daily pain (0 = "no pain" to 10 = "worst possible pain," for the last 24 hours). ⋯ At week 14, the difference in average daily pain score least squares mean vs placebo was -0.41, -0.47, and -0.77, respectively; all mirogabalin groups showed statistical significance. The most common treatment-emergent adverse events were somnolence, nasopharyngitis, dizziness, weight increase, and edema, and all of them were mild or moderate in severity. Mirogabalin was superior to placebo in all groups for relieving PHN and appeared well tolerated.
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Mechanical allodynia is pain caused by normally innocuous mechanical stimuli and is a cardinal and intractable symptom of neuropathic pain. Roles of low-threshold mechanoreceptors (LTMRs), including Aβ fibers, in mechanical allodynia have previously been proposed, but the necessity and sufficiency of LTMRs in allodynia have not been fully determined. Recent technological advances have made it possible to achieve subpopulation-specific ablation, silencing or stimulation, and to dissect and elucidate complex neuronal circuitry. ⋯ Whole-cell recording has revealed that optical Aβ stimulation after nerve injury causes excitation of lamina I dorsal horn neurons, which are normally silent by this stimulation. Moreover, Aβ stimulation after nerve injury results in activation of central amygdaloid neurons and produces aversive behaviors. In summary, these findings indicate that optogenetics is a powerful approach for investigating LTMR-derived pain (resembling mechanical allodynia) with sensory and emotional features after nerve injury and for discovering novel and effective drugs to treat neuropathic pain.
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Randomized Controlled Trial
Effectiveness and safety of 5% lidocaine-medicated plaster on localized neuropathic pain after knee surgery: a randomized, double-blind controlled trial.
Localized neuropathic pain symptoms are reported after knee surgery in 30% to 50% of patients. 5% lidocaine plaster (LP5) is recommended for localized neuropathic pain, but evidence in postsurgery neuropathic pain is missing. This study focuses on the effectiveness of LP5 on allodynia, hyperalgesia, and thermal stimuli in postsurgery knee localized neuropathic pain. A randomized double-blind, 2 parallel groups, controlled trial (NCT02763592) took place in 36 patients (age, 69.4 ± 7.3 years) at the Clinical Pharmacology Center, University Hospital Clermont-Ferrand, France. ⋯ Cold pain and maximal mechanical pain thresholds improved over 3 months (P = 0.001 and P = 0.007, respectively). This study shows for the first time the effectiveness of LP5 on dynamic mechanical allodynia, pain, pressure, and cold thresholds over 3 months in knee localized neuropathic pain. Beyond the inhibition of sodium channels by LP5, these findings suggest the involvement of cold and mechanical receptors that participate to pain chronicisation and also of the non-negligible placebo effect of the patch, items that need to be explored further and challenged in other etiologies of localized neuropathic pain.
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Inhibitory pain modulation has been reported to be deficient in adults across different types of chronic pain, including migraine. To determine whether a similar phenomenon occurs in youth, we performed a quantitative sensory testing investigation in adolescents with migraine (N = 19). These patients were compared to healthy adolescents with (Fam-His; N = 20) or without (Healthy; N = 29) a family history of migraine (eg, first-degree relative with migraine). ⋯ For heat and pressure CPM, there was no significant group difference in the magnitude of CPM responses. Thus, adolescents with migraine and healthy adolescents have similar inhibitory pain modulation capability, despite having marked differences in pain sensitivity. Although Fam-His participants are asymptomatic, they demonstrate alterations in pain processing, which may serve as markers for prediction of migraine development.