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Neuropharmacology. 2017 Sep 15;124:105-120. doi: 10.1016/j.neuropharm.2017.06.015. Epub 2017 Jun 15.

The cannabinoid system and pain.

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Arthritis UK Pain Centre, School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom. Electronic address:
Arthritis UK Pain Centre, School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom.
Pharmacology & Therapeutics, School of Medicine, Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland.
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA; Program in Neuroscience, Indiana University, Bloomington, IN, USA; Interdisciplinary Biochemistry Graduate Program, Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA; Gill Center for Biomolecular Science, Indiana University, Bloomington, IN, USA.
Department of Pharmacology and Neuroscience, Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.


Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics, representing an enormous clinical, societal, and economic burden. Existing pain medications have significant limitations and adverse effects including tolerance, dependence, gastrointestinal dysfunction, cognitive impairment, and a narrow therapeutic window, making the search for novel analgesics ever more important. In this article, we review the role of an important endogenous pain control system, the endocannabinoid (EC) system, in the sensory, emotional, and cognitive aspects of pain. Herein, we briefly cover the discovery of the EC system and its role in pain processing pathways, before concentrating on three areas of current major interest in EC pain research; 1. Pharmacological enhancement of endocannabinoid activity (via blockade of EC metabolism or allosteric modulation of CB1receptors); 2. The EC System and stress-induced modulation of pain; and 3. The EC system & medial prefrontal cortex (mPFC) dysfunction in pain states. Whilst we focus predominantly on the preclinical data, we also include extensive discussion of recent clinical failures of endocannabinoid-related therapies, the future potential of these approaches, and important directions for future research on the EC system and pain. This article is part of the Special Issue entitled "A New Dawn in Cannabinoid Neurobiology".


AA-5-HT (PubChem CID: 10027372); Amygdala; BIA-102474 (PubChem CID: 46831476); Cannabinoid; Cortical control of pain; Endocannabinoid; FAAH; JZL184 (PubChem CID: 25021165); JZL195 (PubChem CID: 46232606); MAGL; MJN110 (PubChem CID: 71722059); PF-04457845 (PubChem CID: 24771824); Pain; Stress; Stress-induced analgesia; Stress-induced hyperalgesia; URB597 (PubChem CID: 1383884); URB937 (PubChem CID: 53394762); mGluR5; mPFC

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