European journal of pain : EJP
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Randomized Controlled Trial
Minocycline reduces experimental muscle hyperalgesia induced by repeated nerve growth factor injections in humans: A placebo-controlled double-blind drug-crossover study.
Hyperalgesia is a heightened pain response to a noxious stimulus and is a hallmark of many common neuropathic and chronic pain conditions. In a double-blind placebo-controlled drug-crossover trial, the effects of concomitant and delayed minocycline treatment on the initiation and resolution of muscle hyperalgesia were tested. ⋯ In a double-blind placebo-controlled drug-crossover study, the common antibiotic minocycline was found to reduce the muscle hyperalgesia induced by intramuscular injection of nerve growth factor. The results of the study showed that both concomitant (pre-emptive) and delayed administration of minocycline can ameliorate the onset and facilitate the resolution of experimentally induced muscle hyperalgesia.
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Randomized Controlled Trial
GABAergic modulation of Secondary hyperalgesia: A randomized controlled 4-way crossover trial with the α2-subunit preferring GABA positive allosteric modulator, N-Desmethyl-Clobazam in healthy volunteers.
The antihyperalgesic and sedative effects of the α2-subunit preferring GABAA positive allosteric modulator (GAM), N-desmethyl-clobazam (NDMC), 20 and 60 mg, were assessed in a randomized, placebo and active-controlled (clonazepam 1,5 mg), 4-way crossover study, in healthy volunteers, using the ultraviolet B-induced experimental pain model. Single (20, 40, 60 mg) and repeated doses (20 mg over 15 days) of NDMC pharmacokinetics were evaluated. Thirty-two subjects participated in the study. ⋯ NDMC absence of sedative effect and its overall well-characterized safety coming from years of utilization as a metabolite from clobazam, raise the prospect of dose escalating trials in patients to quantify its clinical utility. SIGNIFICANCE: This article, presenting the Phase I data of the new antihyperalgesic compound, α2-subunit GABAA positive allosteric modulator, N-desmethyl-clobazam (NDMC) is exploring the modulation of a new target in the treatment of neuropathic pain. Based on these results and on its preclinical properties NDMC would qualify as a good tool compound to seek confirmation of the clinical utility of selective GABA allosteric modulators in neuropathic pain patients.
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Randomized Controlled Trial
Anodal transcranial direct current stimulation over the primary motor cortex attenuates capsaicin-induced dynamic mechanical allodynia and mechanical pain sensitivity in humans.
Anodal transcranial direct current stimulation over the primary cortex has been shown to activate regions of the brain involved in the descending modulation of pain sensitivity. However, more research is required to dissect the spinal cord analgesic mechanisms associated with the development of central sensitization. ⋯ This research shows new evidence that anodal tDCS over the primary motor cortex can reduce dynamic and static forms of mechanical pain sensitivity in the capsaicin model of ongoing pain. By using this approach, it may be possible to provide mechanism-driven analgesia in chronic pain patients who have dynamic mechanical allodynia and/or secondary mechanical hyperalgesia.
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Spontaneous pain after surgical incision is a significant problem for most post-operative patients. Pain management that relies on opioids is hindered by numerous side effects, fuelling interest in non-opioid alternatives and multimodal approaches. Subcutaneous capsaicin infiltration has shown potential for reducing post-operative pain, but there are unanswered questions about safety and possible side effects. In adult rats, we characterized the analgesic effects of pre-operative capsaicin infiltration into the skin prior to plantar incision and assessed wound healing and epidermal innervation. ⋯ Pre-operative capsaicin infiltration attenuated spontaneous pain-like behaviour and prevented the development of heat hyperalgesia following plantar skin incision. While capsaicin caused long-lasting and widespread loss of epidermal and dermal nerve fibres, there was no measurable impact on the rate of wound healing. Pre- or intra-operative infiltration of capsaicin into surgical sites could act as a safe prophylactic for post-operative pain and reduce the need for opioids during recovery.
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There are various approaches to the psychological management of chronic pain and it is difficult to know which components of psychological therapies are necessary or desirable for the effective management of chronic pain. ⋯ The expert consensus indicated that psycho-education, strategies to increase activity and cognitive therapy strategies were necessary for effective psychological treatment of patients with chronic pain. While other strategies were deemed desirable, psychological treatments should include at least those three components.