Pain
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In healthy adults, expectations can modulate the activity of inhibitory bulbo-spinal projections, and can even block the analgesic properties of counter-irritation - a phenomenon that triggers descending inhibition. Since descending inhibition is known to be deficient in fibromyalgia (FM) patients, we tested the possibility that expectancy-mediated analgesia would improve, or even kick-start, the deficient inhibitory responses of FM patients. By measuring subjective pain ratings, spinal withdrawal reflexes, and somatosensory evoked potentials (SEP), it was possible to test whether or not expectancy-mediated analgesia involved descending inhibition in FM patients. ⋯ However, even when analgesia was experienced, the spinal activity of FM patients was abnormal, showing heightened reflex responses. This demonstrates that, unlike healthy subjects, the modulation of pain by expectations in FM fails to influence spinal activity. These results indicate that FMs are capable of expectancy-induced analgesia but that, for them, this form of analgesia does not depend on the recruitment of descending inhibitory projections.
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The neural mechanisms whereby placebo conditioning leads to placebo analgesia remain unclear. In this study we aimed to identify the brain structures activated during placebo conditioning and subsequent placebo analgesia. We induced placebo analgesia by associating a sham treatment with pain reduction and used fMRI to measure brain activity associated with three stages of the placebo response: before, during and after the sham treatment, while participants anticipated and experienced brief laser pain. ⋯ However, during altered pain experience only aMCC, post-central gyrus and posterior cingulate demonstrated altered activity. The common frontal cortical areas modulated during anticipation in both the placebo conditioning and placebo analgesia phases have previously been implicated in placebo analgesia. Our results suggest that the main effect of placebo arises from the reduction of anticipation of pain during placebo conditioning that is subsequently maintained during placebo analgesia.
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Endogenous pain control is, in part, mediated by descending inhibition of spinal nociception via spinal release of noradrenaline. Antinociception by activation of descending noradrenergic fibres has partially been attributed to the direct inhibition of nociceptive spinal neurons. Here, we tested the alternative hypothesis: the direct excitation of inhibitory spinal interneurons by noradrenaline. ⋯ Hyperpolarisations of EGFP- and non-EGFP-labelled neurons were abolished by the alpha(2)-adrenoceptor antagonist yohimbine (2 microM). These results show that noradrenaline directly excites inhibitory (GABAergic) lamina II interneurons in addition to its inhibitory effect on (putatively excitatory) interneurons in superficial spinal dorsal horn. Both effects of noradrenaline constitute a synergism in descending inhibition of nociceptive information in the spinal dorsal horn.
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Patients with chronic pain disorders often show somatosensory disturbances that are considered to be functional. This paper aims at a more precise clinical description and at a documentation of functional neuroimaging correlates of this phenomenon. We examined 30 consecutive patients with unilaterally accentuated chronic pain not explained by persistent peripheral tissue damage and ipsilateral somatosensory disturbances including upper and lower extremities and trunk. ⋯ Conventional imaging procedures (brain CT or MRI scans) showed no structural changes. However, in 11 patients functional imaging with FDG-PET showed a significant hypometabolic pattern of changes in cortical and subcortical areas, mainly in the post-central gyrus, posterior insula, putamen, and anterior cingulate cortex. In summary, pain-related nondermatomal somatosensory deficits (NDSDs) are a phenomenon involving biological as well as psychosocial factors with replicable neuroperceptive clinical findings and a complex neurodysfunctional pattern in the FDG-PET.
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After peripheral nerve damage macrophages infiltrate the dorsal root ganglia (DRG) in which cell bodies of lesioned neurons are located. However, infiltration of macrophages into the DRGs was also reported in complete Freund's adjuvant (CFA)-induced inflammation raising the question whether CFA inflammation induces nerve cell damage or whether peripheral inflammation may also trigger macrophage infiltration into DRGs. Related questions are, first, which signals trigger macrophage infiltration into DRGs and, second, is macrophage infiltration correlated with pain-related behavior. ⋯ Tumor necrosis factor-alpha (TNF-alpha) neutralization with etanercept or infliximab treatment after induction of AIA significantly reduced both macrophage infiltration and VCAM-1 expression. It also decreased mechanical hyperalgesia at the inflamed joint although the joint inflammation itself was barely attenuated, and it reduced mechanical hyperalgesia at the non-inflamed contralateral knee joint. Thus, bilateral segment-specific infiltration of macrophages into DRGs is part of an unilateral inflammatory process in peripheral tissue and it may be involved in the generation of hyperalgesia in particular on the non-inflamed side.