Pain
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Review
Emerging therapies for neuropathic pain: new molecules or new indications for old treatments?
Neuropathic pain represents a highly unmet medical need because most of the available treatments have a modest efficacy or dose-limiting side effects. Hence, novel therapeutic perspectives are warranted. Many compounds acting on new pain targets are in preclinical or early clinical development. ⋯ Another type of emerging drug therapy in neuropathic pain is represented by drugs largely used for other indications, such as botulinum toxin A and the antiepileptic oxcarbazepine, which have recently found to be effective in peripheral neuropathic pain. Emerging nondrug medical therapy with promising results in neuropathic pain also encompasses noninvasive brain neurostimulation techniques, such as repetitive transcranial magnetic stimulation and transcranial direct electrical stimulation. In this article, we review emerging medical treatments for neuropathic pain that are clinically available or with promising results from clinical trials.
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A strong link between histone deacetylases (HDACs) and nociceptive hypersensitivity has been indicated in different pain models. However, the underlying molecular and cellular mechanisms remain elusive. Here, we discovered that partial sciatic nerve ligation-induced mechanical allodynia and thermal hyperalgesia in mice were associated with increased mRNA and protein expressions of HDAC5 (a member of class IIa HDACs) and SRY-related HMG-box 10 (SOX10) in the ipsilateral lumbar dorsal horn. ⋯ Chromatin-immunoprecipitation assay further confirmed a novel nonhistone modulation function of HDACs on SOX10 expression, that is, HDAC5 regulates SOX10 by binding to the promoter region of Sox10 gene. In conclusion, this study for the first time demonstrates that HDAC5 regulates spinal neuronal sensitization in neuropathic pain by upregulating modulating SOX10 expression. Thus, interventions that reduce HDAC5/SOX10 expression may represent promising avenues in the treatment of neuropathic pain.
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Global burden of disease studies measure the impact of disability and premature death resulting from specific diseases and injuries. Recently, these studies have highlighted the leading contribution of regional pain conditions (low back pain and neck pain in particular) to the global burden of disability. However, to date, there has not been a systematic approach to measuring the global burden of disease attributable to neuropathic pain (NP) conditions. This article gives a brief overview of the concept of burden of disease, the underlying drivers, and dynamics of disease burden at a population level and proposes an agenda in relation to NP for developing the conceptual and empirical evidence base necessary for estimating the global burden of NP.
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Air pollution is linked to increased emergency department visits for headache and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well understood. We previously reported that chronic environmental irritant exposure sensitizes the trigeminovascular system response to nasal administration of environmental irritants. Here, we examine whether chronic environmental irritant exposure induces migraine behavioral phenotypes. ⋯ Sumatriptan, an acute migraine treatment blocked acute blood flow changes in response to TRPA1 or transient receptor potential vanilloid receptor-1 agonists. Pretreatment with valproic acid, a prophylactic migraine treatment, attenuated the enhanced blood flow responses observed after acrolein inhalation exposures. Environmental irritant exposure yields an animal model of chronic migraine in which to study mechanisms for enhanced headache susceptibility after chemical exposure.
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Research shows that chronic pain is related to cortical alterations that can be reflected in reduced tactile acuity, but whether acute pain perception influences tactile acuity has not been tested. Considering the biological role of nociception, it was hypothesized that nociceptive pain will lead to a rapid improvement in tactile acuity and that this effect is correlated with pain intensity and pain distribution. In this randomised double-blind controlled experiment (trial no. ⋯ Other tests, point-to-point test and two-point estimation task, changed with a similar trend but did not reach significance. We concluded that acute, nociceptive pain does not improve but deteriorates tactile acuity linearly. The biological role of the observed phenomenon is unknown, and therefore, future studies should address this question.