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The influence of the descending pain modulatory system on infant pain-related brain activity.

ABSTRACT: The descending pain modulatory system (DPMS) constitutes a network of widely distributed brain regions whose integrated function is essential for effective modulation of sensory input to the central nervous system and behavioural responses to pain. Animal studies demonstrate that young rodents have an immature DPMS, but comparable studies have not been conducted in human infants. In Goksan et al. (2015) we used functional MRI (fMRI) to show that pain-related brain activity in newborn infants is similar to that observed in adults. Here, we investigated whether the functional network connectivity strength across the infant DPMS influences the magnitude of this brain activity. FMRI scans were collected while mild mechanical noxious stimulation was applied to the infant's foot. Greater pre-stimulus functional network connectivity across the DPMS was significantly associated with lower noxious-evoked brain activity (p = 0.0004, r = -0.86, n = 13), suggesting that in newborn infants the DPMS may regulate the magnitude of noxious-evoked brain activity.

SUBMITTER: Goksan S

PROVIDER: S-EPMC6133549 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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The influence of the descending pain modulatory system on infant pain-related brain activity.

Goksan Sezgi S Baxter Luke L Moultrie Fiona F Duff Eugene E Hathway Gareth G Hartley Caroline C Tracey Irene I Slater Rebeccah R

eLife 20180911

The descending pain modulatory system (DPMS) constitutes a network of widely distributed brain regions whose integrated function is essential for effective modulation of sensory input to the central nervous system and behavioural responses to pain. Animal studies demonstrate that young rodents have an immature DPMS, but comparable studies have not been conducted in human infants. In Goksan et al. (2015) we used functional MRI (fMRI) to show that pain-related brain activity in newborn infants is ...[more]

PMID: 30201093

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Project description:Background: Opioid long-term therapy can produce tolerance, opioid-induced hyperalgesia (OIH), and it induces dysfunction in pain descending pain inhibitory system (DPIS). Objectives: This integrative review with meta-analysis aimed: (i) To discuss the potential mechanisms involved in analgesic tolerance and opioid-induced hyperalgesia (OIH). (ii) To examine how the opioid can affect the function of DPIS. (ii) To show evidence about the tDCS as an approach to treat acute and chronic pain. (iii) To discuss the effect of tDCS on DPIS and how it can counter-regulate the OIH. (iv) To draw perspectives for the future about the tDCS effects as an approach to improve the dysfunction in the DPIS in chronic non-cancer pain. Methods: Relevant published randomized clinical trials (RCT) comparing active (irrespective of the stimulation protocol) to sham tDCS for treating chronic non-cancer pain were identified, and risk of bias was assessed. We searched trials in PubMed, EMBASE and Cochrane trials databases. tDCS protocols accepted were application in areas of the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), or occipital area. Results: Fifty-nine studies were fully reviewed, and 24 with moderate to the high-quality methodology were included. tDCS improved chronic pain with a moderate effect size [pooled standardized mean difference; -0.66; 95% confidence interval (CI) -0.91 to -0.41]. On average, active protocols led to 27.26% less pain at the end of treatment compared to sham [95% CI; 15.89-32.90%]. Protocol varied in terms of anodal or cathodal stimulation, areas of stimulation (M1 and DLPFC the most common), number of sessions (from 5 to 20) and current intensity (from 1 to 2 mA). The time of application was 20 min in 92% of protocols. Conclusion: In comparison with sham stimulation, tDCS demonstrated a superior effect in reducing chronic pain conditions. They give perspectives that the top-down neuromodulator effects of tDCS are a promising approach to improve management in refractory chronic not-cancer related pain and to enhance dysfunctional neuronal circuitries involved in the DPIS and other pain dimensions and improve pain control with a therapeutic opioid-free. However, further studies are needed to determine individualized protocols according to a biopsychosocial perspective.

Project description:IntroductionResting state functional connectivity (FC) is widely used to assess functional brain alterations in patients with chronic pain. However, reports of FC accompanying tonic pain in pain-free persons are rare. A network we term the Descending Pain Modulatory Network (DPMN) is implicated in healthy and pathologic pain modulation. Here, we evaluate the effect of tonic pain on FC of specific nodes of this network: anterior cingulate cortex (ACC), amygdala (AMYG), periaqueductal gray (PAG), and parabrachial nuclei (PBN).MethodsIn 50 pain-free participants (30F), we induced tonic pain using a capsaicin-heat pain model. functional MRI measured resting BOLD signal during pain-free rest with a 32 °C thermode and then tonic pain where participants experienced a previously warm temperature combined with capsaicin. We evaluated FC from ACC, AMYG, PAG, and PBN with correlation of self-report pain intensity during both states. We hypothesized tonic pain would diminish FC dyads within the DPMN.ResultsOf all hypothesized FC dyads, only PAG and subgenual ACC was weakly altered during pain (F = 3.34; p = 0.074; pain-free>pain d = 0.25). After pain induction sACC-PAG FC became positively correlated with pain intensity (R = 0.38; t = 2.81; p = 0.007). Right PBN-PAG FC during pain-free rest positively correlated with subsequently experienced pain (R = 0.44; t = 3.43; p = 0.001). During pain, this connection's FC was diminished (paired t=-3.17; p = 0.0026). In whole-brain analyses, during pain-free rest, FC between left AMYG and right superior parietal lobule and caudate nucleus were positively correlated with subsequent pain. During pain, FC between left AMYG and right inferior temporal gyrus negatively correlated with pain. Subsequent pain positively correlated with right AMYG FC with right claustrum; right primary visual cortex and right temporo-occipitoparietal junction CONCLUSION: We demonstrate sACC-PAG tonic pain FC positively correlates with experienced pain and resting right PBN-PAG FC correlates with subsequent pain and is diminished during tonic pain. Finally, we reveal PAG- and right AMYG-anchored networks which correlate with subsequently experienced pain intensity. Our findings suggest specific connectivity patterns within the DPMN at rest are associated with subsequently experienced pain and modulated by tonic pain. These nodes and their functional modulation may reveal new therapeutic targets for neuromodulation or biomarkers to guide interventions.

Project description:IntroductionThe association between descending pain modulatory system (DPMS) dysfunction and fibromyalgia has been previously described, but more studies are required on its relationship with aberrant functional connectivity (FC) between the motor and prefrontal cortices.ObjectivesThe objective of this cross-sectional observational study was to compare the intra- and interhemispheric FC between the bilateral motor and prefrontal cortices in women with fibromyalgia, comparing responders and nonresponders to the conditioned pain modulation (CPM) test.MethodsA cross-sectional sample of 37 women (23 responders and 14 nonresponders to the CPM test) with fibromyalgia diagnosed according to the American College of Rheumatology criteria underwent a standardized clinical assessment and an FC analysis using functional near-infrared spectroscopy. DPMS function was inferred through responses to the CPM test, which were induced by hand immersion in cold water (0-1°C). A multivariate analysis of covariance for main effects between responders and nonresponders was conducted using the diagnosis of multiple psychiatric disorders and the use of opioid and nonopioid analgesics as covariates. In addition, we analyzed the interaction between the CPM test response and the presence of multiple psychiatric diagnoses.ResultsNonresponders showed increased FC between the left motor cortex (lMC) and the left prefrontal cortex (lPFC) (t = -2.476, p = 0.01) and right prefrontal cortex (rPFC) (t = -2.363, p = 0.02), even when both were considered as covariates in the regression analysis (lMC-lPFC: β = -0.127, t = -2.425, p = 0.021; lMC-rPFC: β = -0.122, t = -2.222, p = 0.033). Regarding main effects, a significant difference was only observed for lMC-lPFC (p = 0.035). A significant interaction was observed between the psychiatric disorders and nonresponse to the CPM test in lMC-lPFC (β = -0.222, t = -2.275, p = 0.03) and lMC-rPFC (β = -0.211, t = -2.2, p = 0.035). Additionally, a significant interaction was observed between the CPM test and FC in these two region-of-interest combinations, despite the psychiatric diagnoses (lMC-lPFC: β = -0.516, t = -2.447, p = 0.02; lMC-rPFC: β = -0.582, t = -2.805, p = 0.008).ConclusionsHigher FC between the lMC and the bilateral PFC may be a neural marker of DPMS dysfunction in women with fibromyalgia, although its interplay with psychiatric diagnoses also seems to influence this association.

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The influence of the descending pain modulatory system on infant pain-related brain activity.

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The influence of the descending pain modulatory system on infant pain-related brain activity.

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