Cannabinoids in the descending pain modulatory circuit: Role in inflammation

Bouchet, Courtney A.; Ingram, Susan

doi:10.1016/j.pharmthera.2020.107495

Cited by 29 publications

(24 citation statements)

References 237 publications

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“…PAG is the center, RVM is the relay station, and then it goes down to the dorsal horn of spinal cord through the dorsal lateral tract of spinal cord to regulate pain. As a descending nerve fiber that extends from the reticular structure to the spinal cord’s anterior horn cells, this descending inhibitory system whose neurons are housed within many different nuclei such as the nucleus raphe magnus, the nucleus raphe dorsalis, the locus ceruleus, the periaqueductal gray, the reticular formation, the hypothalamus and the somatosensory cortex, is actively involved in transmitting peripheral nociceptive sensation to the central nervous system ( Kuner, 2010 , Bouchet and Ingram, 2020 ).…”

Section: Dysfunction In Descending Nociceptive Modulatory Systemsmentioning

confidence: 99%

Research progress on the mechanism of chronic neuropathic pain

Cui

Liu

Yue

et al. 2023

IBRO Neuroscience Reports

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Section: Dysfunction In Descending Nociceptive Modulatory Systemsmentioning

confidence: 99%

Research progress on the mechanism of chronic neuropathic pain

Cui

Liu

Yue

et al. 2023

IBRO Neuroscience Reports

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“…CB1 receptor is present in the peripheral and central nervous system, including primary sensory neurons in the DRGs, the spinal cord, and some brain regions related to pain processing (Bouchet and Ingram, 2020). Early study showed co-localization of CB1 and MOR in lamina II neurons in the spinal cord (Salio et al, 2001), and synergistic interactions also existed between cannabinoid and opioid analgesia (Raehal and Bohn, 2014).…”

Section: Mor-cb1 Heterodimersmentioning

confidence: 99%

Mu Opioid Receptor Heterodimers Emerge as Novel Therapeutic Targets: Recent Progress and Future Perspective

Zhang

Hang

et al. 2020

Front. Pharmacol.

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Opioids are the most effective analgesics used in the clinical management of cancer pain or non-cancer pain. However, chronic opioids therapy can cause many side effects including respiratory depression, nausea, sedation, itch, constipation, analgesic tolerance, hyperalgesia, high addictive potential, and abuse liability. Opioids exert their effects through binding to the opioid receptors belonging to the G-protein coupled receptors (GPCRs) family, including mu opioid receptor (MOR), delta opioid receptor (DOR), and kappa opioid receptor (KOR). Among them, MOR is essential for opioidinduced analgesia and also responsible for adverse effects of opioids. Importantly, MOR can form heterodimers with other opioid receptors and non-opioid receptors in vitro and in vivo, and has distinct pharmacological properties, different binding affinities for ligands, downstream signaling, and receptor trafficking. This mini review summarized recent progress on the function of Mu opioid receptor heterodimers, and we proposed that targeting mu opioid receptor heterodimers may represent an opportunity to develop new therapeutics, especially for chronic pain treatment.

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“…The CB1 receptor is highly expressed throughout the periaqueductal gray (Wilson-Poe et al, 2012). CFA treatment leads to a decrease in CB1R-mediated suppression of synaptic inhibition in vlPAG of rats (Bouchet and Ingram, 2020), and repeated cannabinoid exposures may downregulate CB1R in the rat brain (Breivogel et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Chronic THC vapor inhalation rescues hyperalgesia in rats with chronic inflammation and produces sex-specific alterations in midbrain neuronal activity

Kelley

Middleton

Gilpin

et al. 2021

Preprint

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To reduce reliance on opioids for the treatment of pain in the clinic, ongoing work is testing the utility of cannabinoid drugs as a potential alternative for treatment of chronic pain and/or as a strategy for reducing opioid drug dosage and duration of treatment (i.e., so-called opioid-sparing effects). Previous preclinical work has shown robust anti-hyperalgesic effects of systemic THC and acute anti-hyperalgesic effects of vaporized THC. Here, we used a vapor inhalation model in rats to test chronic THC vapor inhalation effects on thermal nociception and mechanical sensitivity, as well as midbrain (i.e., periaqueductal gray [PAG]) neuronal function, in adult male rats with chronic inflammatory pain. We report that chronic THC vapor inhalation produces a robust anti-hyperalgesic effect in rats with chronic inflammatory pain, and that this effect persists 24 hours after cessation of THC exposure. We demonstrate that chronic THC vapor inhalation also modulates intrinsic and synaptic properties of ventrolateral PAG (vlPAG) neurons, including reductions in action potential firing rate and reductions in spontaneous inhibitory synaptic transmission, and that these effects occur specifically in neurons that respond to current input with a delayed firing phenotype. Finally, we show that the suppressive effect of the bath-applied mu-opioid receptor (MOR) agonist DAMGO on synaptic inhibition in the vlPAG is enhanced in slices taken from rats with a history of chronic THC vapor inhalation. Collectively, these data show that chronic THC vapor inhalation produces lasting attenuation of thermal hyperalgesia and reduces synaptic inhibition in the vlPAG of rats with chronic inflammatory pain.

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Cannabinoids in the descending pain modulatory circuit: Role in inflammation

Cited by 29 publications

References 237 publications

Research progress on the mechanism of chronic neuropathic pain

Research progress on the mechanism of chronic neuropathic pain

Mu Opioid Receptor Heterodimers Emerge as Novel Therapeutic Targets: Recent Progress and Future Perspective

Chronic THC vapor inhalation rescues hyperalgesia in rats with chronic inflammation and produces sex-specific alterations in midbrain neuronal activity

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