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Brain mediators of predictive cue effects on perceived pain.

ABSTRACT: Information about upcoming pain strongly influences pain experience in experimental and clinical settings, but little is known about the brain mechanisms that link expectation and experience. To identify the pathways by which informational cues influence perception, analyses must jointly consider both the effects of cues on brain responses and the relationship between brain responses and changes in reported experience. Our task and analysis strategy were designed to test these relationships. Auditory cues elicited expectations for barely painful or highly painful thermal stimulation, and we assessed how cues influenced human subjects' pain reports and brain responses to matched levels of noxious heat using functional magnetic resonance imaging. We used multilevel mediation analysis to identify brain regions that (1) are modulated by predictive cues, (2) predict trial-to-trial variations in pain reports, and (3) formally mediate the relationship between cues and reported pain. Cues influenced heat-evoked responses in most canonical pain-processing regions, including both medial and lateral pain pathways. Effects on several regions correlated with pretask expectations, suggesting that expectancy plays a prominent role. A subset of pain-processing regions, including anterior cingulate cortex, anterior insula, and thalamus, formally mediated cue effects on pain. Effects on these regions were in turn mediated by cue-evoked anticipatory activity in the medial orbitofrontal cortex (OFC) and ventral striatum, areas not previously directly implicated in nociception. These results suggest that activity in pain-processing regions reflects a combination of nociceptive input and top-down information related to expectations, and that anticipatory processes in OFC and striatum may play a key role in modulating pain processing.

SUBMITTER: Atlas LY

PROVIDER: S-EPMC2966558 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Brain mediators of predictive cue effects on perceived pain.

Atlas Lauren Y LY Bolger Niall N Lindquist Martin A MA Wager Tor D TD

The Journal of neuroscience : the official journal of the Society for Neuroscience 20100901 39

Information about upcoming pain strongly influences pain experience in experimental and clinical settings, but little is known about the brain mechanisms that link expectation and experience. To identify the pathways by which informational cues influence perception, analyses must jointly consider both the effects of cues on brain responses and the relationship between brain responses and changes in reported experience. Our task and analysis strategy were designed to test these relationships. Aud ...[more]

PMID: 20881115

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Project description:The current crises in opioid abuse and chronic pain call for the development of nonopioid and nonpharmacological therapeutics for pain relief. Neuromodulation-based approaches, such as spinal cord stimulation, dorsal root ganglion simulation, and nerve stimulation including vagus nerve stimulation, have shown efficacy in achieving pain control in preclinical and clinical studies. However, the mechanisms by which neuromodulation alleviates pain are not fully understood. Accumulating evidence suggests that neuromodulation regulates inflammation and neuroinflammation-a localized inflammation in peripheral nerves, dorsal root ganglia/trigeminal ganglia, and spinal cord/brain-through neuro-immune interactions. Specialized proresolving mediators (SPMs) such as resolvins, protectins, maresins, and lipoxins are lipid molecules produced during the resolution phase of inflammation and exhibit multiple beneficial effects in resolving inflammation in various animal models. Recent studies suggest that SPMs inhibit inflammatory pain, postoperative pain, neuropathic pain, and cancer pain in rodent models via immune, glial, and neuronal modulations. It is noteworthy that sham surgery is sufficient to elevate resolvin levels and may serve as a model of resolution. Interestingly, it has been shown that the vagus nerve produces SPMs and vagus nerve stimulation (VNS) induces SPM production in vitro. In this review, we discuss how neuromodulation such as VNS controls pain via immunomodulation and neuro-immune interactions and highlight possible involvement of SPMs. In particular, we demonstrate that VNS via auricular electroacupuncture effectively attenuates chemotherapy-induced neuropathic pain. Furthermore, auricular stimulation is able to increase resolvin levels in mice. Thus, we propose that neuromodulation may control pain and inflammation/neuroinflammatioin via SPMs. Finally, we discuss key questions that remain unanswered in our understanding of how neuromodulation-based therapies provide short-term and long-term pain relief.

Dataset Information

Brain mediators of predictive cue effects on perceived pain.

Publications

Brain mediators of predictive cue effects on perceived pain.

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