Pain
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Randomized Controlled Trial
Baroreflex sensitivity associated hypoalgesia in healthy states is altered by chronic pain.
While experimental baroreceptor stimulation is known to elicit hypoalgesia in healthy individuals, the impact of spontaneous baroreflex sensitivity (BRS) on acute pain responses is not known. We tested for associations between BRS and pain responses in healthy individuals, whether these associations are altered in chronic low back pain (CLBP), and the role of alpha-2 adrenergic (ADRA2) mechanisms in these effects. Twenty-five healthy controls and 21 CLBP subjects completed three acute pain tasks after receiving placebo or an intravenous ADRA2 antagonist (yohimbine hydrochloride, 0.4 mg/kg) across two sessions in counterbalanced order. ⋯ In contrast, CLBP subjects displayed a nonsignificant positive BRS/pain association under placebo, with yohimbine producing an inverse association similar to controls (significant for MPQ-Sensory). Results suggest presence of spontaneous BRS-related hypoalgesia in healthy individuals that is partially mediated by ADRA2 mechanisms, and that CLBP blunts BRS-related hypoalgesia. As a group, the CLBP subjects do not manifest baroreceptor-induced antinociception.
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The mechanisms of nociception in the low back are poorly understood, partly because systematic recordings from dorsal horn neurons with input from the low back are largely missing. The purpose of this investigation was to (1) identify spinal segments and dorsal horn neurons receiving input from the low back, (2) test the effect of nerve growth factor (NGF) injected into the multifidus muscle (MF) on the neurons' responsiveness, and (3) study the influence of a chronic MF inflammation on the responses. In rats, microelectrode recordings were made in the segments L2, L3, and L5 to find dorsal horn neurons having input from the low back (LB neurons). ⋯ The centers of the neurons' receptive fields (RFs) were consistently located 2-3 segments caudally relative to their recording site. The results show that (1) input convergence from various tissues is common for LB neurons, (2) the input from structures of the low back is processed 2-3 segments cranially relative to the vertebral level of the RFs, and (3) the responsiveness of LB neurons is increased during a pathologic alteration of the MF. The above findings may be relevant for some cases of chronic low back pain in patients.
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The vast majority of the experimental pain studies have used acute, phasic heat stimuli to investigate the neurobiological mechanisms of pain. However, the validity of these models for understanding clinical forms of pain is questionable. We here describe the characteristics of a model of prolonged tonic heat pain stimulation and compared the responses on this test with other measures of pain. ⋯ Tonic heat pain ratings only correlated moderately with the pain threshold while stronger correlations were observed with pain tolerance and ratings of suprathreshold phasic heat pain. We conclude that the tonic heat model is a suitable model that can be applied without excessive discomfort in the majority of subjects and offers a valuable addition to the armamentarium of experimental pain models. The model can be particularly suitable for brain imaging receptor binding studies which require long stimulation periods.
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Review Meta Analysis
Hypoalgesia in schizophrenia is independent of antipsychotic drugs: a systematic quantitative review of experimental studies.
Diminished sensitivity to pain in schizophrenia has been reported since the early works of Bleuler [Bleuler E. Textbook of psychiatry (trans. Brill HA, 1951). ⋯ This meta-analysis substantiates the hypothesis of a diminished pain response in schizophrenia. The study also suggests that hypoalgesia in schizophrenia cannot be solely explained by the effects of antipsychotic drugs, and that it may not be a pain-specific blunted response. Further studies are warranted to determine the clinical and biological correlates, and the social and health consequences, of hypoalgesia in schizophrenia.
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Randomized Controlled Trial Multicenter Study
Exposure in vivo versus operant graded activity in chronic low back pain patients: results of a randomized controlled trial.
Since pain-related fear may contribute to the development and maintenance of chronic low back pain (CLBP), an exposure in vivo treatment (EXP) was developed for CLBP patients. We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant graded activity (GA) directly and 6 months post-treatment in a multi-centre randomized controlled trial. In total, 85 patients suffering from disabling non-specific CLBP reporting at least moderate pain-related fear were randomly allocated to EXP or GA. ⋯ Furthermore, the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities. In sum, this study demonstrates that up to 6 months after treatment EXP is an effective treatment, but not more effective than GA, in moderately to highly fearful CLBP patients, although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established. Possible explanations for these findings are discussed.