title: The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain.
abstract: The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressed cannabinoid receptor 2 (CB₂). It is found in relatively high concentrations in many spices and food plants. A number of studies have shown that CB₂ is critically involved in the modulation of inflammatory and neuropathic pain responses. In this study, we have investigated the analgesic effects of BCP in animal models of inflammatory and neuropathic pain. We demonstrate that orally administered BCP reduced inflammatory (late phase) pain responses in the formalin test in a CB₂ receptor-dependent manner, while it had no effect on acute (early phase) responses. In a neuropathic pain model the chronic oral administration of BCP attenuated thermal hyperalgesia and mechanical allodynia, and reduced spinal neuroinflammation. Importantly, we found no signs of tolerance to the anti-hyperalgesic effects of BCP after prolonged treatment. Oral BCP was more effective than the subcutaneously injected synthetic CB₂ agonist JWH-133. Thus, the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions.
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Sigmund-Freud-Straße 25, D-53127 Bonn, Germany.
authors.forename: A-L
authors.initials: AL
authors.lastname: Klauke
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Sigmund-Freud-Straße 25, D-53127 Bonn, Germany. Electronic address: iracz@uni-bonn.de.
authors.forename: I
authors.initials: I
authors.lastname: Racz
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Sigmund-Freud-Straße 25, D-53127 Bonn, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Pradier
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Sigmund-Freud-Straße 25, D-53127 Bonn, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Markert
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Sigmund-Freud-Straße 25, D-53127 Bonn, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Zimmer
authors.affiliation: Institute of Biochemistry and Molecular Medicine, NCCR TransCure, University of Bern, CH-3012 Bern, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Gertsch
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Sigmund-Freud-Straße 25, D-53127 Bonn, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Zimmer
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010147:Pain Measurement; D064209:Phytochemicals / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000081223:Polycyclic Sesquiterpenes; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D063386:Cannabinoid Receptor Agonists; C571431:Cnr2 protein, mouse; D009419:Nerve Tissue Proteins; D064209:Phytochemicals; D000081223:Polycyclic Sesquiterpenes; D043885:Receptor, Cannabinoid, CB2; D012717:Sesquiterpenes; C024714:caryophyllene
keywords: Beta-caryophyllene; CB(2); Dietary cannabinoid; Inflammatory pain; Neuropathic pain