Antiallodynic effect of β-caryophyllene on paclitaxel-induced peripheral neuropathy in mice. (October 2017)

• Record Type: Journal Article
• Authors: Segat, Gabriela C.; Manjavachi, Mariane N.; Matias, Daiane O.; Passos, Giselle F.; Freitas, Cristina Setim; Costa, Robson; Calixto, João B.
• Is Part Of: Neuropharmacology. Volume 125(2017)
• Page Start: 207
• Page End: 219
• Publication Date: 2017-10
• Subjects: Neuropathic pain -- Paclitaxel -- Cannabinoid -- β-caryophyllene; BCP β-caryophyllene -- CB2 Cannabinoid type-2 receptor -- CIPN Chemotherapy-induced peripheral neuropathy -- CNS Central Nervous System -- MCP-1 Monocyte Chemoattractant Protein 1 -- PINP Paclitaxel-induced peripheral neuropathy -- PTX Paclitaxel -- PWT paw withdrawal threshold; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2017.07.015
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Painful peripheral neuropathy is a common side effect of paclitaxel (PTX). The use of analgesics is an important component for management of PTX-induced peripheral neuropathy (PINP). However, currently employed analgesics have several side effects and are poorly effective. β-caryophyllene (BCP), a dietary selective CB2 agonist, has shown analgesic effect in neuropathic pain models, but its role in chemotherapy-induced neuropathic pain has not yet been investigated. Herein, we used the mouse model of PINP to show the therapeutic effects of BCP in this neuropathy. Male Swiss mice receiving PTX (2 mg kg −1, ip, four alternate days) were treated with BCP (25 mg kg −1, po, twice a day) either during or after PTX administration. Some groups were also pretreated with AM630 (CB2 antagonist, 3 mg kg −1, ip ) or AM251 (CB1 antagonist, 1 mg kg −1, ip ). Spinal cord samples were collected in different time points to perform immunohistochemical analysis. BCP attenuated the established mechanical allodynia induced by PTX ( p < 0.0001) in a CB2 -dependent manner. Of note, when given concomitantly with PTX, BCP was able to attenuate the development of PINP ( p < 0.0001). Spinal cord immunohistochemistry revealed that preventive treatment with BCP reduced p38 MAPK and NF-κB activation, as well as the increased Iba-1 and IL-1β immunoreactivity promoted by PTX. Our findings show that BCP effectively attenuated PINP, possibly through CB2 -activation in the CNS and posterior inhibition of p38 MAPK/NF-κB activation and cytokine release. Taken together, our results suggest that BCP could be used to attenuate the establishment and/or treat PINP. Graphical abstract: Highlights: Oral treatment with β-caryophyllene (BCP) reduced PTX-induced peripheral neuropathy. BCP was able to attenuate the development of mechanical allodynia induced by PTX. The attenuating effect of BCP depends on inhibition of spinal cord inflammation.