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      Journal of Pain Research (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of high-quality laboratory and clinical findings in all fields of pain research and the prevention and management of pain. Sign up for email alerts here.

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      Is Open Access

      Cannabinoids and spinal cord stimulation for the treatment of failed back surgery syndrome refractory pain

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          Abstract

          Objective

          This study aimed to evaluate pain and its symptoms in patients with failed back surgery syndrome (FBSS) refractory to other therapies, treated with a combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in association with spinal cord stimulation (SCS).

          Settings

          Outpatients referred at Pain Unit of San Vincenzo Hospital in Taormina (Italy), between September 2014 and January 2016.

          Subjects

          Eleven FBSS patients diagnosed with neuropathic pain using the Douleur Neuropathique 4 questionnaire and suffering from moderate to severe chronic refractory pain, and undergoing treatment with SCS and a combination of THC/CBD for 12 consecutive months.

          Materials and methods

          All the included patients discontinued previous unsuccessful therapy at least 2 months before the beginning of the cannabinoid therapy, with the exception of the SCS that was continued. Patients received a fixed dosage of cannabinoid agonists (THC/CBD) that could be increased subjective to pain control response. A Brief Pain Inventory questionnaire was administered to measure pain and its interference with characteristic dimensions of feelings and functions. The duration of treatment with SCS and THC/CBD combination was 12 months.

          Results

          Effective pain management as compared to baseline result was achieved in all the cases studied. The positive effect of cannabinoid agonists on refractory pain was maintained during the entire duration of treatment with minimal dosage titration. Pain perception, evaluated through numeric rating scale, decreased from a baseline mean value of 8.18±1.07–4.72±0.9 by the end of the study duration (12 months) ( P<0.001).

          Conclusion

          The results indicate that cannabinoid agonists (THC/CBD) can have remarkable analgesic capabilities, as adjuvant of SCS, for the treatment of chronic refractory pain of FBSS patients.

          Most cited references33

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          The orphan receptor GPR55 is a novel cannabinoid receptor.

          The endocannabinoid system functions through two well characterized receptor systems, the CB1 and CB2 receptors. Work by a number of groups in recent years has provided evidence that the system is more complicated and additional receptor types should exist to explain ligand activity in a number of physiological processes. Cells transfected with the human cDNA for GPR55 were tested for their ability to bind and to mediate GTPgammaS binding by cannabinoid ligands. Using an antibody and peptide blocking approach, the nature of the G-protein coupling was determined and further demonstrated by measuring activity of downstream signalling pathways. We demonstrate that GPR55 binds to and is activated by the cannabinoid ligand CP55940. In addition endocannabinoids including anandamide and virodhamine activate GTPgammaS binding via GPR55 with nM potencies. Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB1 or CB2 activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55. GPR55 couples to Galpha13 and can mediate activation of rhoA, cdc42 and rac1. These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB1 and CB2 described here will permit delineation of its physiological function(s).
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            Agonistic properties of cannabidiol at 5-HT1a receptors.

            Cannabidiol (CBD) is a major, biologically active, but psycho-inactive component of cannabis. In this cell culture-based report, CBD is shown to displace the agonist, [3H]8-OH-DPAT from the cloned human 5-HT1a receptor in a concentration-dependent manner. In contrast, the major psychoactive component of cannabis, tetrahydrocannabinol (THC) does not displace agonist from the receptor in the same micromolar concentration range. In signal transduction studies, CBD acts as an agonist at the human 5-HT1a receptor as demonstrated in two related approaches. First, CBD increases [35S]GTPgammaS binding in this G protein coupled receptor system, as does the known agonist serotonin. Second, in this GPCR system, that is negatively coupled to cAMP production, both CBD and 5-HT decrease cAMP concentration at similar apparent levels of receptor occupancy, based upon displacement data. Preliminary comparative data is also presented from the cloned rat 5-HT2a receptor suggesting that CBD is active, but less so, relative to the human 5-HT1a receptor, in binding analyses. Overall, these studies demonstrate that CBD is a modest affinity agonist at the human 5-HT1a receptor. Additional work is required to compare CBD's potential at other serotonin receptors and in other species. Finally, the results indicate that cannabidiol may have interesting and useful potential beyond the realm of cannabinoid receptors.
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              Cannabis, Cannabinoids, and Sleep: a Review of the Literature.

              The current review aims to summarize the state of research on cannabis and sleep up to 2014 and to review in detail the literature on cannabis and specific sleep disorders from 2014 to the time of publication.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2018
                06 September 2018
                : 11
                : 1761-1767
                Affiliations
                [1 ]Anesthesia, Intensive Care and Pain Therapy, Azienda Ospedaliera Universitaria “G Martino” Messina – University of Messina, Messina, Italy
                [2 ]Pain Therapy Unit, San Vincenzo Hospital, Azienda Sanitaria Provinciale Messina, Messina, Italy
                [3 ]Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy, gcalapai@ 123456unime.it
                [4 ]Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
                Author notes
                Correspondence: Gioacchino Calapai, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria 5, 98125 Messina, Italy, Tel +39 090 221 3646, Email gcalapai@ 123456unime.it
                Article
                jpr-11-1761
                10.2147/JPR.S166617
                6134407
                30233233
                71573dcd-7d0a-467e-81e6-f42a3fb99c17
                © 2018 Mondello et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Anesthesiology & Pain management
                cannabinoids,delta-9-tetrahydrocannabinol,thc,cannabidiol,cbd,failed back surgery syndrome,fbss,refractory pain,spinal cord stimulation,scs,cannabis

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