Brain, behavior, and immunity
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Brain Behav. Immun. · May 2013
Randomized Controlled TrialLow-dose endotoxin potentiates capsaicin-induced pain in man: evidence for a pain neuroimmune connection.
Despite the wealth of evidence in animals that immune activation has a key role in the development and maintenance of chronic pain, evidence to support this in humans is scant. We have sought such evidence by examining the effect of a subtle immunological stimulus, low dose intravenous endotoxin, on the allodynia, hyperalgesia, flare and pain produced by intradermal capsaicin in healthy volunteers. ⋯ These data demonstrate clinically a significant role for the neuroimmune pain connection in modifying pain, thus providing evidence that immune priming may produce pain enhancement in humans and hence offer a novel range of pharmacological targets for anti-allodynics and/or analgesics. Additionally, the simplicity of the model makes it suitable as a test-bed for novel immune-targeted pain therapeutics.
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Brain Behav. Immun. · Feb 2012
Randomized Controlled TrialSingle-trial conditioning in a human taste-endotoxin paradigm induces conditioned odor aversion but not cytokine responses.
Immunological responses to bacterial endotoxin can be behaviorally conditioned in rodents. However, it is unclear whether an acute systemic inflammatory response can be behaviorally conditioned in humans. Thus, in a double-blind placebo-controlled study, 20 healthy, male subjects received either a single injection of lipopolysaccharide (LPS) or saline together with a novel tasting beverage (conditioned stimulus, CS). ⋯ Sole presentation of the CS during evocation did induce neither alterations in body temperature nor changes in plasma cytokine levels. However, subjects in the experimental group rated the smell of the CS significantly more aversive compared to the control group. Employing endotoxin as a US in a single trial taste-immune conditioning paradigm in humans shows a behaviorally conditioned smell aversion but no learned alterations in cytokine levels.
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Brain Behav. Immun. · May 2006
Randomized Controlled TrialPlacebo effects in laser-evoked pain potentials.
Placebo treatment may affect multiple components of pain, including inhibition of nociceptive input, automatic or deliberative appraisal of pain, or cognitive judgments involved in pain reporting. If placebo analgesia is due in part to an attenuation of early nociceptive processing, then pain-evoked event-related potentials (ERPs) should be reduced with placebo. In this study, we tested for placebo effects in P2 laser-evoked potentials at midline scalp electrodes. ⋯ However, we also found evidence that the very robust placebo-induced decreases in reported pain are not solely explained by early reductions in P2. N2 amplitude was affected by neither placebo nor reduction of laser intensity. These results suggest that placebo treatment affects early nociceptive processing, but that another component of placebo effects in reported pain occurs later, either in evaluation of pain or cognitive judgments about pain reports.
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Brain Behav. Immun. · Jan 2006
Randomized Controlled TrialBelief or Need? Accounting for individual variations in the neurochemistry of the placebo effect.
The activation of pain-suppressive, endogenous opioid neurotransmission after administration of a placebo with expectation of analgesia has been directly demonstrated in humans using molecular imaging techniques in recent work. Regional effects were described in the dorsolateral prefrontal cortex, pregenual anterior cingulate, anterior insula, and nucleus accumbens. However, it was also observed that the magnitude of these responses was subject to substantial individual and regional variation. ⋯ A model that included affective qualities of pain, the volume of algesic stimulus required to maintain pain over the experimental period within a moderate range, and the internal affective state of the volunteers contributed to 40-68% of the variance in the regional neurochemical responses to placebo. These initial data suggests that in the case of endogenous opioid mediated placebo analgesic responses, the individual experience of pain, in particular its affective elements, the internal affective state of the individuals during pain and a measure of sustained pain sensitivity are important factors contributing to the formation of a placebo effect. Further examination of individual variations in placebo responding will need to take into account the underlying process for which relief is required.