Repeated Morphine Administration Increases TRPV1 mRNA Expression and Autoradiographic Binding at Supraspinal Sites in the Pain Pathway

Repeated morphine administration induces tolerance to its analgesic effects. A previous study reported that repeated morphine treatment activates transient receptor potential vanilloid type 1 (TRPV1) expression in the sciatic nerve, dorsal root ganglion, and spinal cord, contributing to morphine tolerance. In the present study, we analyzed TRPV1 expression and binding sites in supraspinal pain pathways in morphine-tolerant mice. The TRPV1 mRNA levels and binding sites were remarkably increased in the cortex and thalamus of these animals. Our data provide additional insights into the effects of morphine on TRPV1 in the brain and suggest that changes in the expression of, and binding to TRPV1 in the brain are involved in morphine tolerance.

[1]  J. Novotný,et al.  β-Arrestin 2 and ERK1/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and µ-Opioid Receptors in the Plasma Membrane , 2020, International journal of molecular sciences.

[2]  A. Shamsizadeh,et al.  The role of locus coeruleus nucleus TRPV1 receptors in the development and expression of morphine dependence , 2019, Iranian journal of basic medical sciences.

[3]  T. Hales,et al.  Perioperative opioid analgesia—when is enough too much? A review of opioid-induced tolerance and hyperalgesia , 2019, The Lancet.

[4]  Hyoung‐Chun Kim,et al.  TRPV1 modulates morphine self-administration via activation of the CaMKII-CREB pathway in the nucleus accumbens , 2018, Neurochemistry International.

[5]  Hyoung‐Chun Kim,et al.  TRPV1 modulates morphine-induced conditioned place preference via p38 MAPK in the nucleus accumbens , 2017, Behavioural Brain Research.

[6]  V. Yarov-Yarovoy,et al.  A pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1 , 2015, Nature Communications.

[7]  R. Lai,et al.  Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel , 2015, Toxins.

[8]  Hyoung‐Chun Kim,et al.  Transient Receptor Potential Vanilloid Type 1 Channel May Modulate Opioid Reward , 2014, Neuropsychopharmacology.

[9]  N. Bunnett,et al.  Activation of Mu Opioid Receptors Sensitizes Transient Receptor Potential Vanilloid Type 1 (TRPV1) via β-Arrestin-2-Mediated Cross-Talk , 2014, PloS one.

[10]  D. Julius,et al.  Structure of the TRPV1 ion channel determined by electron cryo-microscopy , 2013, Nature.

[11]  G. Pasternak,et al.  Mu Opioids and Their Receptors: Evolution of a Concept , 2013, Pharmacological Reviews.

[12]  R. Lefkowitz,et al.  Therapeutic potential of β-arrestin- and G protein-biased agonists. , 2011, Trends in molecular medicine.

[13]  C. Jang,et al.  Effects of capsazepine, a transient receptor potential vanilloid type 1 antagonist, on morphine-induced antinociception, tolerance, and dependence in mice. , 2010, British journal of anaesthesia.

[14]  D. Julius,et al.  A Bivalent Tarantula Toxin Activates the Capsaicin Receptor, TRPV1, by Targeting the Outer Pore Domain , 2010, Cell.

[15]  S. Maier,et al.  Proinflammatory cytokines oppose opioid-induced acute and chronic analgesia , 2008, Brain, Behavior, and Immunity.

[16]  S. Mackey,et al.  Reduced cold pain tolerance in chronic pain patients following opioid detoxification. , 2008, Pain medicine.

[17]  C. Geis,et al.  Activation of TRPV1 Contributes to Morphine Tolerance: Involvement of the Mitogen-Activated Protein Kinase Signaling Pathway , 2008, The Journal of Neuroscience.

[18]  E. Navratilova,et al.  Sustained morphine treatment augments basal CGRP release from cultured primary sensory neurons in a Raf-1 dependent manner. , 2008, European journal of pharmacology.

[19]  H. Pan,et al.  Resistance to morphine analgesic tolerance in rats with deleted transient receptor potential vanilloid type 1-expressing sensory neurons , 2007, Neuroscience.

[20]  A. Gomtsyan,et al.  TRPV1 Receptors in the CNS Play a Key Role in Broad-Spectrum Analgesia of TRPV1 Antagonists , 2006, The Journal of Neuroscience.

[21]  H. Pan,et al.  Loss of TRPV1-expressing sensory neurons reduces spinal mu opioid receptors but paradoxically potentiates opioid analgesia. , 2006, Journal of neurophysiology.

[22]  S. Hunt,et al.  Role of NK-1 neurotransmission in opioid-induced hyperalgesia , 2005, Pain.

[23]  John B Davis,et al.  [3H]Resiniferatoxin autoradiography in the CNS of wild-type and TRPV1 null mice defines TRPV1 (VR-1) protein distribution , 2004, Brain Research.

[24]  S. Welch,et al.  Modulation of Oral Morphine Antinociceptive Tolerance and Naloxone-Precipitated Withdrawal Signs by Oral Δ9-Tetrahydrocannabinol , 2003, Journal of Pharmacology and Experimental Therapeutics.

[25]  T. Vanderah,et al.  Sustained Morphine Exposure Induces a Spinal Dynorphin-Dependent Enhancement of Excitatory Transmitter Release from Primary Afferent Fibers , 2002, The Journal of Neuroscience.

[26]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[27]  B. Kest,et al.  Morphine tolerance after chronic intracerebroventricular injection in male and female mice , 2001, Brain Research.

[28]  V. Marzo,et al.  New perspectives on enigmatic vanilloid receptors , 2000, Trends in Neurosciences.

[29]  W. Ma,et al.  Morphine treatment induced calcitonin gene-related peptide and substance P increases in cultured dorsal root ganglion neurons , 2000, Neuroscience.

[30]  A. Basbaum,et al.  The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli , 1998, Neuron.

[31]  T. Ness,et al.  The development of tolerance to intrathecal morphine in rat models of visceral and cutaneous pain , 1998, Neuroscience Letters.

[32]  D. Julius,et al.  The capsaicin receptor: a heat-activated ion channel in the pain pathway , 1997, Nature.

[33]  T. Yaksh,et al.  Pharmacology and mechanisms of opioid analgesic activity , 1997, Acta anaesthesiologica Scandinavica.

[34]  G. Pasternak,et al.  Peripheral morphine analgesia: synergy with central sites and a target of morphine tolerance. , 1996, The Journal of pharmacology and experimental therapeutics.

[35]  Lei Yu,et al.  Protein kinase modulation of mu opioid receptor signalling. , 1996, Cellular signalling.

[36]  H. Merskey.  Logic, truth and language in concepts of pain , 1994, Quality of Life Research.

[37]  R. Lobato,et al.  Intrathecal therapy: rationale, technique, clinical results , 1987, Acta anaesthesiologica Scandinavica. Supplementum.

[38]  J. Weston,et al.  Intrathecal and intraventricular morphine for pain in cancer patients: initial study. , 1983, Journal of neurosurgery.

[39]  T. Rudy,et al.  Multiplicative interaction between narcotic agonisms expressed at spinal and supraspinal sites of antinociceptive action as revealed by concurrent intrathecal and intracerebroventricular injections of morphine. , 1980, The Journal of pharmacology and experimental therapeutics.

[40]  Enrique Hernández-García,et al.  Lipid modulation of thermal transient receptor potential channels. , 2014, Current topics in membranes.

[41]  V. Di Marzo,et al.  TRPV1 receptors in the central nervous system: potential for previously unforeseen therapeutic applications. , 2008, Current pharmaceutical design.

[42]  J. Greenspan,et al.  The role of the thalamus in pain. , 2004, Supplements to Clinical neurophysiology.

[43]  M. Takahashi,et al.  Involvement of pain associated anxiety in the development of morphine tolerance in formalin treated mice. , 1994, Japanese journal of pharmacology.

[44]  F. G. Hannington-Kiff.  The mechanisms of pain. , 1979, Nursing.