Dataset Information

Pharmacologic attenuation of cross-modal sensory augmentation within the chronic pain insula.

ABSTRACT: Pain can be elicited through all mammalian sensory pathways yet cross-modal sensory integration, and its relationship to clinical pain, is largely unexplored. Centralized chronic pain conditions such as fibromyalgia are often associated with symptoms of multisensory hypersensitivity. In this study, female patients with fibromyalgia demonstrated cross-modal hypersensitivity to visual and pressure stimuli compared with age- and sex-matched healthy controls. Functional magnetic resonance imaging revealed that insular activity evoked by an aversive level of visual stimulation was associated with the intensity of fibromyalgia pain. Moreover, attenuation of this insular activity by the analgesic pregabalin was accompanied by concomitant reductions in clinical pain. A multivariate classification method using support vector machines (SVM) applied to visual-evoked brain activity distinguished patients with fibromyalgia from healthy controls with 82% accuracy. A separate SVM classification of treatment effects on visual-evoked activity reliably identified when patients were administered pregabalin as compared with placebo. Both SVM analyses identified significant weights within the insular cortex during aversive visual stimulation. These data suggest that abnormal integration of multisensory and pain pathways within the insula may represent a pathophysiological mechanism in some chronic pain conditions and that insular response to aversive visual stimulation may have utility as a marker for analgesic drug development.

SUBMITTER: Harte SE

PROVIDER: S-EPMC4988086 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Pharmacologic attenuation of cross-modal sensory augmentation within the chronic pain insula.

Harte Steven E SE Ichesco Eric E Hampson Johnson P JP Peltier Scott J SJ Schmidt-Wilcke Tobias T Clauw Daniel J DJ Harris Richard E RE

Pain 20160901 9

Pain can be elicited through all mammalian sensory pathways yet cross-modal sensory integration, and its relationship to clinical pain, is largely unexplored. Centralized chronic pain conditions such as fibromyalgia are often associated with symptoms of multisensory hypersensitivity. In this study, female patients with fibromyalgia demonstrated cross-modal hypersensitivity to visual and pressure stimuli compared with age- and sex-matched healthy controls. Functional magnetic resonance imaging re ...[more]

PMID: 27101425

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Project description:Sensory loss induces cross-modal plasticity, often resulting in altered performance in remaining sensory modalities. Whereas much is known about the macroscopic mechanisms underlying cross-modal plasticity, only scant information exists about its cellular and molecular underpinnings. We found that Caenorhabditis elegans nematodes deprived of a sense of body touch exhibit various changes in behavior, associated with other unimpaired senses. We focused on one such behavioral alteration, enhanced odor sensation, and sought to reveal the neuronal and molecular mechanisms that translate mechanosensory loss into improved olfactory acuity. To this end, we analyzed in mechanosensory mutants food-dependent locomotion patterns that are associated with olfactory responses and found changes that are consistent with enhanced olfaction. The altered locomotion could be reversed in adults by optogenetic stimulation of the touch receptor (mechanosensory) neurons. Furthermore, we revealed that the enhanced odor response is related to a strengthening of inhibitory AWC→AIY synaptic transmission in the olfactory circuit. Consistently, inserting in this circuit an engineered electrical synapse that diminishes AWC inhibition of AIY counteracted the locomotion changes in touch-deficient mutants. We found that this cross-modal signaling between the mechanosensory and olfactory circuits is mediated by neuropeptides, one of which we identified as FLP-20. Our results indicate that under normal function, ongoing touch receptor neuron activation evokes FLP-20 release, suppressing synaptic communication and thus dampening odor sensation. In contrast, in the absence of mechanosensory input, FLP-20 signaling is reduced, synaptic suppression is released, and this enables enhanced olfactory acuity; these changes are long lasting and do not represent ongoing modulation, as revealed by optogenetic experiments. Our work adds to a growing literature on the roles of neuropeptides in cross-modal signaling, by showing how activity-dependent neuropeptide signaling leads to specific cross-modal plastic changes in neural circuit connectivity, enhancing sensory performance.

Project description:Joint attention refers to the coordinated attention between social partners to an object of shared interest, usually involving shared gaze toward the object. In the laboratory, however, joint attention is often investigated using computerized gaze cueing tasks that do not allow shared gaze. Instead, these computerized tasks require the participant to maintain fixation on the virtual partner's face, while the partner gazes to the left or right. Here we designed a modified gaze cueing task that better simulates a natural joint attention episode by allowing shared gaze, while still maintaining tight experimental control. In our computerized task the participant's gaze and the gaze of a virtual partner were manipulated independently, resulting in shared or unshared gaze. Following each gaze shift of the virtual partner a touch stimulus was delivered on one of the cheeks of the participant. We analyzed behavioral and neural (electro-encephalography) responses to the touch. Faster reaction-times and stronger lateralization of alpha power were observed when the touched cheek was in a jointly attended hemispace compared with a singly attended or unattended hemispace. Importantly, these effects were unique to joint attention and could not be explained as the additive effects of own gaze and gaze cue direction. Underlining its social nature, we found that the behavioral effect was absent when we repeated our experiment with nonsocial cues (arrows) instead of gaze cues. Furthermore, when we compared trustworthy with untrustworthy virtual partners (trustworthiness judgements based on facial appearance) we found the effect only for trustworthy and not for untrustworthy virtual partners. We conclude that joint attention based on shared gaze influences attentional orienting such that cross-modal sensory processing at the jointly attended location is facilitated, particularly when the partner is trustworthy. This indicates that social interactions and trustworthiness judgements affect cortical and behavioral responses to sensory information.

Dataset Information

Pharmacologic attenuation of cross-modal sensory augmentation within the chronic pain insula.

Publications

Pharmacologic attenuation of cross-modal sensory augmentation within the chronic pain insula.

Similar Datasets

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