ArticleThe journal of pain2017
Sustained Morphine Administration Induces TRPM8-Dependent Cold Hyperalgesia.
Article in The journal of pain, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Control of motor coordination by transient receptor potential melastatin 8 through γ-aminobutyric acidergic circuit modulation in the male mouse cerebellum.Scientific reports · 2025Article
- 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
- β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models.International journal of molecular sciences · 2022Article
- The distinctive role of menthol in pain and analgesia: Mechanisms, practices, and advances.Frontiers in molecular neuroscience · 2022Review
- TRP channels and monoterpenes: Past and current leads on analgesic properties.Frontiers in molecular neuroscience · 2022Review
- TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation.International journal of molecular sciences · 2021Review
- Determining 5HTFrontiers in neuroscience · 2021Article
- Mechanoactivation of NOX2-generated ROS elicits persistent TRPM8 CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Dim Light at Night Exposure Induces Cold Hyperalgesia and Mechanical Allodynia in Male Mice.Neuroscience · 2020Article
- Chronic morphine regulates TRPM8 channels via MOR-PKCβ signaling.Molecular brain · 2020Article
- Selenium and Neurological Diseases: Focus on Peripheral Pain and TRP Channels.Current neuropharmacology · 2020Review
- TRPV1 activity and substance P release are required for corneal cold nociception.Nature communications · 2019Article
- Effects of glucosamine against morphine-induced antinociceptive tolerance and dependence in mice.Journal of biomedical science · 2019Article
- Effects of menthol and its interaction with nicotine-conditioned cue on nicotine-seeking behavior in rats.Psychopharmacology · 2017Article
- The Relationship Between Ocular Itch, Ocular Pain, and Dry Eye Symptoms (An American Ophthalmological Society Thesis).Transactions of the American Ophthalmological Society · 2017Article
- Dual effects of brain sparing opioid in newborn rats: Analgesia and hyperalgesia.Neurobiology of pain (Cambridge, Mass.)Article
- Molecular mechanisms of cold pain.Neurobiology of pain (Cambridge, Mass.)Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
It is not uncommon for patients chronically treated with opioids to exhibit opioid-induced hyperalgesia, and this has been widely reported clinically and experimentally. The molecular substrate for this hyperalgesia is multifaceted, and associated with a complex neural reorganization even in the periphery. For instance, we have recently shown that chronic morphine-induced heat hyperalgesia is associated with an increased expression of GluN2B containing N-methyl-D-aspartate receptors, as well as of the neuronal excitatory amino acid transporter 3/excitatory amino acid carrier 1, in small-diameter primary sensory neurons only. Cold allodynia is also a common complaint of patients chronically treated with opioids, yet its molecular mechanisms remain to be understood. Here we present evidence that the cold sensor TRPM8 channel is involved in opioid-induced hyperalgesia. After 7 days of morphine administration, we observed an upregulation of TRPM8 channels using patch clamp recording on sensory neurons and Western blot analysis on dorsal root ganglia. The selective TRPM8 antagonist RQ-00203078 blocked cold hyperalgesia in morphine-treated rats. Also, TRPM8 knockout mice failed to develop cold hyperalgesia after chronic administration of morphine. Our results show that chronic morphine upregulates TRPM8 channels, which is in contrast with the previous finding that acute morphine triggers TRPM8 internalization. PERSPECTIVE: Patients receiving chronic opioid are sensitive to cold. We show in mice and rats that sustained morphine administration induces cold hyperalgesia and an upregulation of TRPM8. Knockout or selectively blocking TRPM8 reduces morphine-induced cold hyperalgesia suggesting TRPM8 is regulated by opioids.
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Registered trials
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.