D Scuteri1, L Rombolà2, K Hamamura3, T Sakurada4, C Watanabe5, S Sakurada6, F Guida7, S Boccella8, S Maione9, G Gallo Afflitto10, C Nucci11, P Tonin12, G Bagetta13, M T Corasaniti14. 1. Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy; Regional Center for Serious Brain Injuries, S. Anna Institute, 88900 Crotone, Italy. Electronic address: damiana.scuteri@unical.it. 2. Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy. Electronic address: laura.rombola@unical.it. 3. Department of Pharmacology, Daiichi University of Pharmacy, 815-8511 Fukuoka, Japan. Electronic address: k-hamamura@daiichi-cps.ac.jp. 4. Department of Pharmacology, Daiichi University of Pharmacy, 815-8511 Fukuoka, Japan. Electronic address: tsukasa@daiichi-cps.ac.jp. 5. Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 981-8558 Sendai, Japan. Electronic address: chizu@tohoku-mpu.ac.jp. 6. Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 981-8558 Sendai, Japan. Electronic address: s-sakura@tohoku-mpu.ac.jp. 7. Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", 80138 Naples, Italy. Electronic address: franc.guida@gmail.com. 8. Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", 80138 Naples, Italy. Electronic address: boccellaserena@gmail.com. 9. Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", 80138 Naples, Italy; Endocannabinoid Research Group, Institute of Biomolecular Chemistry, CNR, Pozzuoli, Italy; IRCSS, Neuromed, Pozzilli, Italy. Electronic address: sabatino.maione@unicampania.it. 10. Ophthalmology Unit, Department of Experimental Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy. Electronic address: gabrielegalloafflitto@gmail.com. 11. Ophthalmology Unit, Department of Experimental Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy. Electronic address: nucci@med.uniroma2.it. 12. Regional Center for Serious Brain Injuries, S. Anna Institute, 88900 Crotone, Italy. Electronic address: p.tonin@isakr.it. 13. Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy. 14. Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy. Electronic address: mtcorasa@unicz.it.
Abstract
BACKGROUND: Purpose of the present systematic review is to investigate preclinical evidence in favor of the working hypothesis of efficacy of cannabinoids in ocular pain treatment. METHODS: Literature search includes the most relevant repositories for medical scientific literature from inception until November, 24 2021. Data collection and selection of retrieved records adhere to PRISMA criteria. RESULTS: In agreement with a priori established protocol the search retrieved 2471 records leaving 479 results after duplicates removal. Eleven records result from title and abstract screening to meet the inclusion criteria; only 4 results are eligible for inclusion in the qualitative synthesis impeding meta-analysis. The qualitative analysis highlights the antinociceptive and anti-inflammatory efficacy of Δ8-tetrahydrocannabinol, cannabidiol and its derivative HU-308 and of new racemic CB1 allosteric ligand GAT211 and its enantiomers GAT228 and GAT229. Moreover, CB2R agonists RO6871304 and RO6871085 and CB2R ligand HU910 provide evidence of anti-inflammatory efficacy. CB2 agonist HU308 reduces of 241% uveitis-induced leukocyte adhesion and changes lipidome profile. Methodological and design issues raise concern of risk of bias and the amount of studies is too small for generalization. Furthermore, the ocular pain model used can resemble only inflammatory but not neuropathic pain. CONCLUSIONS: The role of the endocannabinoid system in ocular pain is underinvestigated, since only two studies assessing the effects of cannabinoid receptors modulators on pain behavior and other two on pain-related inflammatory processes are found. Preclinical studies investigating the efficacy of cannabinoids in ocular inflammatory and neuropathic pain models are needed to pave the way for clinical translation.
BACKGROUND: Purpose of the present systematic review is to investigate preclinical evidence in favor of the working hypothesis of efficacy of cannabinoids in ocular pain treatment. METHODS: Literature search includes the most relevant repositories for medical scientific literature from inception until November, 24 2021. Data collection and selection of retrieved records adhere to PRISMA criteria. RESULTS: In agreement with a priori established protocol the search retrieved 2471 records leaving 479 results after duplicates removal. Eleven records result from title and abstract screening to meet the inclusion criteria; only 4 results are eligible for inclusion in the qualitative synthesis impeding meta-analysis. The qualitative analysis highlights the antinociceptive and anti-inflammatory efficacy of Δ8-tetrahydrocannabinol, cannabidiol and its derivative HU-308 and of new racemic CB1 allosteric ligand GAT211 and its enantiomers GAT228 and GAT229. Moreover, CB2R agonists RO6871304 and RO6871085 and CB2R ligand HU910 provide evidence of anti-inflammatory efficacy. CB2 agonist HU308 reduces of 241% uveitis-induced leukocyte adhesion and changes lipidome profile. Methodological and design issues raise concern of risk of bias and the amount of studies is too small for generalization. Furthermore, the ocular pain model used can resemble only inflammatory but not neuropathic pain. CONCLUSIONS: The role of the endocannabinoid system in ocular pain is underinvestigated, since only two studies assessing the effects of cannabinoid receptors modulators on pain behavior and other two on pain-related inflammatory processes are found. Preclinical studies investigating the efficacy of cannabinoids in ocular inflammatory and neuropathic pain models are needed to pave the way for clinical translation.
Authors: Maria Resah B Villanueva; Narges Joshaghani; Nicole Villa; Omar Badla; Raman Goit; Samia E Saddik; Sarah N Dawood; Ahmad M Rabih; Ahmad Niaj; Aishwarya Raman; Manish Uprety; Maria Calero; Safeera Khan Journal: Cureus Date: 2022-07-16