Neural circuit basis of placebo pain relief [SMART-seq]
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ABSTRACT:
PROVIDER: PRJNA1110772 | ENA |
REPOSITORIES: ENA
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Project description:For over a millennium, mind-body interactions have fascinated scientists and doctors for their abilities to shape human perceptions of the external world 1,2. Placebo effects are striking demonstrations of mind-body interactions in which, in the absence of any treatment, a positive expectation of pain relief can reduce or even abolish the experience of pain 3–6. However, despite widespread recognition of the strength of placebo effects and their impact on everyday human experience and clinical trials for new analgesics, the neural circuit basis of the placebo effect has remained a mystery. Here, we show that analgesia from the expectation of pain relief is mediated by a distinct population of rostral anterior cingulate cortex (rACC) neurons that project to the pontine nuclei (rACC→Pn), a pair of brainstem pre-cerebellar nuclei with no established function in pain processing. To do this, we created a behavioral assay that models placebo analgesia by conditioning mice to expect pain relief when moving from a chamber with a heated floor to a second chamber. In this assay, an expectation of pain relief induces an analgesic effect that, like placebo analgesia in humans, is mediated by endogenous opioids. Calcium imaging of neural activity in freely moving mice and electrophysiological studies in cingulate cortical brain slices showed that expectations of pain relief boost the activity of rACC→Pn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an unusual abundance of opioid receptors in these cells, further suggesting a role in pain modulation. Selective inhibition of either the rACC→Pn pathway or of opioid-receptor-expressing Pn neurons disrupted placebo analgesia and decreased pain thresholds. Finally, a subset of cerebellar Purkinje cells exhibits activity patterns resembling those of rACC→Pn neurons during pain relief expectation, providing cellular-level evidence of a role for the cerebellum in cognitive pain modulation. Altogether, these findings elucidate longstanding mysteries surrounding the placebo effect by identifying a specific neural pathway that mediates expectation-based pain relief. This discovery opens the possibility of targeting this novel pathway with drugs or neurostimulation methods to treat pain. More broadly, our studies provide a framework for investigating the neural circuit basis of other mind-body interactions beyond those involving pain, and point to prefrontocortical-cerebellar communication as a potential basis for such effects.
2024-09-12 | GSE267264 | GEO
Project description:For over a millennium, mind-body interactions have fascinated scientists and doctors for their abilities to shape human perceptions of the external world 1,2. Placebo effects are striking demonstrations of mind-body interactions in which, in the absence of any treatment, a positive expectation of pain relief can reduce or even abolish the experience of pain 3–6. However, despite widespread recognition of the strength of placebo effects and their impact on everyday human experience and clinical trials for new analgesics, the neural circuit basis of the placebo effect has remained a mystery. Here, we show that analgesia from the expectation of pain relief is mediated by a distinct population of rostral anterior cingulate cortex (rACC) neurons that project to the pontine nuclei (rACC→Pn), a pair of brainstem pre-cerebellar nuclei with no established function in pain processing. To do this, we created a behavioral assay that models placebo analgesia by conditioning mice to expect pain relief when moving from a chamber with a heated floor to a second chamber. In this assay, an expectation of pain relief induces an analgesic effect that, like placebo analgesia in humans, is mediated by endogenous opioids. Calcium imaging of neural activity in freely moving mice and electrophysiological studies in cingulate cortical brain slices showed that expectations of pain relief boost the activity of rACC→Pn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an unusual abundance of opioid receptors in these cells, further suggesting a role in pain modulation. Selective inhibition of either the rACC→Pn pathway or of opioid-receptor-expressing Pn neurons disrupted placebo analgesia and decreased pain thresholds. Finally, a subset of cerebellar Purkinje cells exhibits activity patterns resembling those of rACC→Pn neurons during pain relief expectation, providing cellular-level evidence of a role for the cerebellum in cognitive pain modulation. Altogether, these findings elucidate longstanding mysteries surrounding the placebo effect by identifying a specific neural pathway that mediates expectation-based pain relief. This discovery opens the possibility of targeting this novel pathway with drugs or neurostimulation methods to treat pain. More broadly, our studies provide a framework for investigating the neural circuit basis of other mind-body interactions beyond those involving pain, and point to prefrontocortical-cerebellar communication as a potential basis for such effects.
2024-09-12 | GSE267265 | GEO
Project description:Neural circuit basis of placebo pain relief [10X]
| PRJNA1110771 | ENA
Project description:Chronic pain is a major health care problem with great social and economic consequences. Although the medial prefrontal cortex (mPFC) and the thalamus have been implicated in regulating pain, whether and how these regions may involve in pain chronification process have remained largely unknown. Here, we show that Foxp2+ neurons in mPFC, which are corticothalamic (CT) neurons representing the major mPFC output to thalamus, are deactivated in chronic inflammatory pain. Interestingly, prolonged, but not short-term, inactivation of the Foxp2+ neurons in mPFC increases the sensitivity to noxious stimulations. Conversely, chemogenetic activation of this neuronal cluster induces robust antinociceptive effects in both naïve mice and mice with chronic inflammatory pain. Furthermore, we found that the mPFC Foxp2+ neurons project to several thalamic relay nuclei and that activation of the mPFC to the parataenial nucleus of thalamus (PTN) circuit relieves pain. Finally, RNA-seq of the mPFC Foxp2+ neurons revealed that many genes related to neuronal activity are dysregulated in mice with chronic inflammatory pain. Collectively, our studies revealed that Foxp2+ neurons in mPFC that project to thalamus play a critical role in somatosensory processing and pain chronification.
2023-09-16 | GSE243136 | GEO
Project description:A genetically defined mPFC-thalamic circuit underlies pain chronicity
| PRJNA1016417 | ENA
Project description:This study aims to identify the molecular mechanism in the sensory cortex underlying pain-relief effect of electroacupuncture
2021-01-09 | E-MTAB-9987 | biostudies-arrayexpress
Project description:Neuropathic pain causes severe suffering and most patients are resilient to current therapies. A core element of neuropathic pain is the loss of inhibitory tone in the spinal cord. Previous studies have shown that foetal GABAergic neuron precursors can provide relief from pain. However, the source of these precursor cells and their multipotent status make them unsuitable for therapeutic use. Here we extend these findings by showing, for the first time, that spinally transplanted, terminally differentiated hiPSC-derived GABAergic (iGABAergic) neurons provide significant, long-term and safe relief from neuropathic pain induced by peripheral nerve injury in mice. Furthermore, iGABAergic Neuron transplants survive long term in the injured spinal cord and show evidence of synaptic integration. Together, this provides the proof in principle for the first viable GABAergic transplants to treat human neuropathic pain patients.
2020-01-23 | GSE115565 | GEO
Project description:To study effects the Quell device has on opioid consumption and pain relief in patients with cancer.
| 2218031 | ecrin-mdr-crc
Project description:Interventions: Experimental group:Xenopus capsule + Oxycontin;The control group:Placebo + OxyContin
Primary outcome(s): Pain relief rate
Study Design: Parallel
| 47840 | ecrin-mdr-crc
Project description:(2R,6R)-Hydroxynorketamine restores postsynaptic localization of AMPAR in the prelimbic cortex to provide sustained pain relief
| PRJNA899841 | ENA