Articles: neuropathic-pain.
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Recent evidence of neuropathic pain among adults with sickle cell disease (SCD) reveals a need for adjuvant analgesic treatments for these patients. Ca(2+)/calmodulin protein kinase IIα (CaMKIIα) has a known role in neuropathic pain and trifluoperazine is a potent CaMKIIα inhibitor. The study aim was to determine trifluoperazine's acute effects, primarily on adverse effects and secondarily on pain intensity reduction, in adults with SCD. ⋯ Sedation resolved with caffeine and dystonia resolved with diphenhydramine. Adults with SCD experienced minimal adverse effects at doses under 10mg. In this molecular mechanism-driven translational study, trifluoperazine shows promise as an analgesic drug that is worthy of further testing in a randomized controlled study of adults with SCD starting at a dose of 1mg in repeated doses to determine long-term adverse and analgesic effects.
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SIP30 (SNAP25 interacting protein of 30) is a SNAP25 interaction protein of 30 kDa that functions in neurotransmitter release. Using a chronic constriction injury (CCI) model of neuropathic pain, we profiled gene expression in the rat spinal cord and brain and identified sip30, which was upregulated after CCI. Here, we show that CCI induced a bilateral increase of SIP30 in the rostral anterior cingulate cortex (rACC), a key brain region that has been implicated in pain affect. ⋯ Intra-rACC administration of PKA or ERK inhibitors suppressed CCI-induced SIP30 upregulation and blocked the induction of PEAP. Additionally, knockdown of SIP30 suppressed the frequency of mEPSCs and increased paired-pulse ratios in rACC slices and decreased extracellular glutamate concentrations. Together, our results highlight SIP30 as a target of PKA and ERK in the rACC to mediate neuropathic pain-evoked negative emotion via modulation of glutamate release and excitatory synaptic transmission.
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Progesterone (PROG) is promising as an important protective agent against various injuries to the nervous system. The present study was designed to investigate whether starting PROG administration, when symptomatology is already established, would alleviate the expression of nociceptive behaviors (mechanical allodynia and thermal hyperalgesia) and electrophysiological changes in a chronic constriction injury (CCI) model of neuropathic pain in rats. Male rats were given PROG (1.5, 3, 6 and 12 mg/kg, i.p.) 12 days after CCI induction, and dosing continued daily until day 26. ⋯ PROG at doses of 6 or 12 mg/kg induced a significant recovery of all electrophysiological changes. Our data indicated that starting PROG therapy when symptomatology is already established, and continuing it for a sufficient period of time, may have a therapeutic effect. This suggests that PROG may offer new strategies for the treatment of neuropathic pain.
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Transcranial magnetic stimulation (TMS) is a non-invasive method for activating specific areas of the brain. There are two variants, repetitive TMS (rTMS) and direct TMS. Rapid changes in an electrical current induce a magnetic field, which in turn induces an electrical current in a nearby conductor. ⋯ French physicians have shown a high level of interest in rTMS, and the first French recommendations for using this method were issued in 2011. Further research is needed to determine the optimal stimulation parameters, session frequency, and session duration, as well as the best indications. Physicians who see many patients with chronic pain, such as rheumatologists, should be aware of this developing non-pharmacological and safe treatment modality, which can be of considerable help to their patients.
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Journal of pain research · Jan 2014
Scientometric assessment of drugs for chronic pain, 1979-2013: rapid growth of publications, paucity of successful drugs.
The aim of this study was to find signs of progress in the pharmacotherapy of chronic pain over the past 35 years using scientometric analysis. The following scientometric indices were used: 1) popularity index, representing the share of articles on a specific drug(s) relative to all articles in the field of chronic pain; 2) index of change, representing the degree of growth in publications on a topic from one period to the next; 3) index of expectations, representing the ratio of the number of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed; and 4) index of ultimate success, representing a publication outcome when a new drug takes the place of a common drug previously used for the same purpose. Publications on 55 drugs used in the treatment of chronic pain were assessed during seven 5-year periods, from 1979 to 2013. ⋯ None of the drugs had a high index of expectations in 2009-2013. The index of ultimate success was positive only with triptans in the relatively limited area of acute treatment of migraine. As a result, despite rapid growth in the number of publications, our scientometric analysis did not reveal signs of substantial progress in the field of pharmacotherapy for chronic pain.