Pain
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Drugs that inhibit reuptake of monoamines are frequently used to treat pain syndromes, e.g. neuropathy or fibromyalgia, where mechanical allodynia is present. Several lines of evidence suggest the involvement of supraspinal sites of action of these drugs. However, a direct study of supraspinal serotonin (5-HT) or norepinephrine (NE) release in an animal model in which allodynia is expressed, e.g. neuropathy, has not been done. ⋯ This study is the first to demonstrate changes in monoamine release supraspinally in NP rats. The differential effect between VB thalamus and hypothalamus suggests that a terminal field change may be involved. Putative mechanisms for mediating this change include alterations of GABA-ergic systems and/or plasticity related to alterations in N-methyl-D-aspartate receptor activation and nitric oxide release related to afferent hyperactivity induced by neuropathic pain.
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A systematic review and subset meta-analysis of published randomised controlled trials of psychological therapies for children and adolescents with chronic pain is reported. A search of four computerised abstracting services recovered 123 papers from which 28 potential trials were identified. Eighteen met the criteria for inclusion in the review. ⋯ Meta-analysis was applicable for 12 headache trials and one trial of recurrent abdominal pain using the Pain Index. The odds-ratio for a 50% reduction in pain was 9.62 and the number needed to treat was 2.32, indicating that the psychological treatments examined are effective in reducing the pain of headache. The quality of the 18 trials retrieved is narratively reviewed and suggestions for the development of trials in this field are made.
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Randomized Controlled Trial Clinical Trial
Sensory stimulation (TENS): effects of parameter manipulation on mechanical pain thresholds in healthy human subjects.
Transcutaneous electrical nerve stimulation (TENS) is a popular form of electrostimulation. Despite an extensive research base, there remains no consensus regarding the parameter selection required to achieve maximal hypoalgesic effects. The aim of this double blind, sham-controlled study was to investigate the relative hypoalgesic effects of different TENS parameters (frequency, intensity and stimulation site) upon experimentally induced mechanical pain. ⋯ Whilst high frequency, 'strong but comfortable' intensity, segmental stimulation produced comparable hypoalgesic levels during stimulation, this effect was not sustained post-stimulation. Stimulation at a combination of the two sites did not produce any greater hypoalgesic effects. These results may have implications for the clinical use of sensory stimulation.
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The pain modulatory role of dopamine D2 receptors of the human forebrain was studied by determining the association between dopamine D2 receptor binding potential and the response to experimental pain. Nineteen healthy male volunteers participated in a dopamine D2 receptor positron emission tomography study. The extrastriatal regions of interest studied with [11C]FLB 457 as radioligand (n = 11) were the anterior cingulum, the medial and lateral thalamus, the medial and lateral frontal cortex, and the medial and lateral temporal cortex. ⋯ A psychophysical control study (n = 10) showed that cold pain responses were identical in the right and left hand. The results indicate that dopamine D2 receptor binding potential in the human forebrain, particularly in the striatum, may be an important parameter in determining the individual cold pain response and the potential for central pain modulation. Accordingly, an individual with only few available D2 receptors in the forebrain is likely to have a high tonic level of pain suppression, combined with a low capacity to recruit more (dopaminergic) central pain inhibition by noxious conditioning stimulation.
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Comparative Study
Micromolar lidocaine selectively blocks propagating ectopic impulses at a distance from their site of origin.
Abnormal impulses caused by very slowly inactivating Na channels of peripheral nerve have been proposed to play a critical role in neuropathic pain. Low concentrations of local anesthetics, often effective in treating experimental and clinical neuropathic pain, are also known to potently suppress the long after-depolarizations induced by these persistently open Na channels. However, these drug actions on impulses that have propagated away from such sites are undetermined. ⋯ Tetrodotoxin also inhibited the induced spontaneous activity, but only at concentrations that also depressed the compound action potential spike. These findings show that low concentrations of lidocaine can restore normal firing patterns in nerve where hyperexcitability has been caused by delayed Na-channel inactivation, without acting directly at the site where ectopic impulses are generated. Thus, it appears that the pattern of abnormal activity rather than an abnormally gating Na channel per se can be a target for lidocaine's therapeutic action.