Pain
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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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This study examined gender differences in the effect of experimental muscle pain on changes in the relative activation of regions of the upper trapezius muscle during a sustained contraction. Surface electromyographic (EMG) signals were recorded from multiple locations over the upper trapezius muscle with a 10 x 5 grid of electrodes from nine women and nine men during 90 degrees shoulder abduction sustained for 60s. Measurements were performed before and after the injection of 0.4 ml hypertonic (painful) and isotonic (control) saline into the cranial region of the upper trapezius muscle. ⋯ During the non-painful sustained contractions, the EMG RMS progressively increased more in the cranial than the caudal region, for both men and women, due to fatigue. This mechanism was maintained in men but not in women during the painful condition. The results demonstrate that muscle pain alters the normal adaptation of upper trapezius muscle activity to fatigue in women but not in men.
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Peripheral nerve injuries that provoke neuropathic pain are associated with microglial activation in the spinal cord. We have investigated the characteristics of spinal microglial activation in three distinct models of peripheral neuropathic pain in the rat: spared nerve injury (SNI), chronic constriction injury, and spinal nerve ligation. In all models, dense clusters of cells immunoreactive for the microglial marker CD11b formed in the ipsilateral dorsal horn 7 days after injury. ⋯ Early intrathecal treatment with low-dose methotrexate, beginning at the time of injury, decreased microglial activation, reduced p38 phosphorylation, and attenuated pain-like behavior after SNI. In contrast, systemic or intrathecal delivery of the glucocorticoid dexamethasone did not inhibit the activation of microglia or reduce pain-like behavior. We confirm that microglial activation is crucial for the development of pain after nerve injury, and demonstrates that suppression of this cellular immune response is a promising approach for preventing neuropathic pain.
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Preclinical drug development for visceral pain has largely relied on quantifying pseudoaffective responses to colorectal distension (CRD) in restrained rodents. However, the predictive value of changes in simple reflex responses in rodents for the complex human pain experience is not known. Male rats were implanted with venous cannulas and with telemetry transmitters for abdominal electromyographic (EMG) recordings. [(14)C]-iodoantipyrine was injected during noxious CRD (60 mmHg) in the awake, nonrestrained animal. ⋯ Our findings support the validity of measurements of cerebral perfusion during CRD in the freely moving rat as a model of functional brain changes in human visceral pain. However, not all regions demonstrating significant group differences correlated with EMG or behavioral measures. This suggests that functional brain imaging captures more extensive responses of the central nervous system to noxious visceral distension than those identified by traditional measures.
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HIV associated sensory neuropathy is a common neurological disorder with reported prevalence of 53%. When only small fibers are involved, the diagnosis of neuropathy remains difficult since standard nerve conduction studies generally are unremarkable. We assessed a method to identify small-fiber neuropathy using electrically evoked pain-related potentials and correlated the electrophysiological results with intraepidermal nerve fiber density in patients with HIV associated sensory neuropathy. ⋯ Pain-related evoked potentials revealed abnormalities in all HIV positive neuropathy patients, while standard nerve conduction testing was abnormal in eight patients only. Pain-related evoked potential latencies and amplitudes strongly correlated with intraepidermal nerve fiber density. The method of pain-related evoked potential conduction appears to be a sensitive, fast, non-invasive technique for the detection of small-fiber neuropathy and may prove to become a valuable diagnostic asset.