ArticleMolecular brain2020
Chronic morphine regulates TRPM8 channels via MOR-PKCβ signaling.
Article in Molecular brain, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Bryostatins 1 and 3 inhibit TRPM8 and modify TRPM8- and TRPV1-mediated lung epithelial cell responses to a proinflammatory stimulus via protein kinase C.Molecular pharmacology · 2025Article
- TRPM8's Role in the Shift Between Opioid and Cannabinoid Pathways in Electroacupuncture for Inflammatory Pain in Mice.International journal of molecular sciences · 2024Article
- Navigating the Controversies: Role of TRPM Channels in Pain States.International journal of molecular sciences · 2024Review
- Cold nociception as a measure of hyperalgesia during spontaneous heroin withdrawal in mice.Pharmacology, biochemistry, and behavior · 2024Article
- Interaction of Calmodulin with TRPM: An Initiator of Channel Modulation.International journal of molecular sciences · 2023Review
- Ion Channel Genes in Painful Neuropathies.Biomedicines · 2023Review
- PKC regulation of ion channels: The involvement of PIPThe Journal of biological chemistry · 2022Review
- The distinctive role of menthol in pain and analgesia: Mechanisms, practices, and advances.Frontiers in molecular neuroscience · 2022Review
- Mechanisms Underlying Mu Opioid Receptor Effects on Parallel Fiber-Purkinje Cell Synaptic Transmission in Mouse Cerebellar Cortex.Frontiers in synaptic neuroscience · 2022Article
- Constitutive Phosphorylation as a Key Regulator of TRPM8 Channel Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation.International journal of molecular sciences · 2021Review
- PKCε stimulation of TRPV1 orchestrates carotid body responses to asthmakines.The Journal of physiology · 2021Article
- The cool things to know about TRPM8!Channels (Austin, Tex.) · 2020Review
- Negative Modulation of TRPM8 Channel Function by Protein Kinase C in Trigeminal Cold Thermoreceptor Neurons.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Postoperative shivering and cold hypersensitivity are major side effects of acute and chronic opioid treatments respectively. TRPM8 is a cold and menthol-sensitive channel found in a subset of dorsal root ganglion (DRG) nociceptors. Deletion or inhibition of the TRPM8 channel was found to prevent the cold hyperalgesia induced by chronic administration of morphine. Here, we examined the mechanisms by which morphine was able to promote cold hypersensitivity in DRG neurons and transfected HEK cells. Mice daily injected with morphine for 5 days developed cold hyperalgesia. Treatment with morphine did not alter the expressions of cold sensitive TREK-1, TRAAK and TRPM8 in DRGs. However, TRPM8-expressing DRG neurons isolated from morphine-treated mice exhibited hyperexcitability. Sustained morphine treatment in vitro sensitized TRPM8 responsiveness to cold or menthol and reduced activation-evoked desensitization of the channel. Blocking phospholipase C (PLC) as well as protein kinase C beta (PKCβ), but not protein kinase A (PKA) or Rho-associated protein kinase (ROCK), restored channel desensitization. Identification of two PKC phosphorylation consensus sites, S1040 and S1041, in the TRPM8 and their site-directed mutation were able to prevent the MOR-induced reduction in TRPM8 desensitization. Our results show that activation of MOR by morphine 1) promotes hyperexcitability of TRPM8-expressing neurons and 2) induces a PKCβ-mediated reduction of TRPM8 desensitization. This MOR-PKCβ dependent modulation of TRPM8 may underlie the onset of cold hyperalgesia caused by repeated administration of morphine. Our findings point to TRPM8 channel and PKCβ as important targets for opioid-induced cold hypersensitivity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.