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Title: Effects of cannabinoid type 2 receptor agonist on the development of nucleoside reverse transcriptase inhibitor-induced neuropathic pain in mice
Authors: Esraa Mohamed Abbas Aly 
Supervisor: Dr. Willias Masocha
Degree Awarded: Degree in Pharmaceutical Sciences
Keywords: Neuropathic pain; Nucleoside reverse transcriptase inhibitor; Cytokines; ddC; Phytocannabinoid; β-caryophyllene; Antiretroviral; Mechanical allodynia; CB2 receptor; Glial cells.
Issue Date: 2020
Publisher:  Kuwait university - college of graduate studies
Abstract: Neuropathic pain associated with nucleoside reverse transcriptase inhibitors (NRTIs), therapeutic agents for human immunodeficiency virus (HIV), responds poorly to the currently available drugs. Cannabis, which activates cannabinoid type 1 (CB1) and CB2 receptors, has been reported to relieve HIV-associated neuropathic pain in clinical trials. However, the activation of the CB1 receptor is associated with side effects such as psychosis and physical dependence. Therefore, I investigated the antiallodynic effects of β-caryophyllene (BCP), a CB2 selective phytocannabinoid, in a mouse model of NRTI-induced neuropathic pain. Female BALB/c mice treated with 2′-3′- dideoxycytidine (ddC, zalcitabine), a NRTI, for 5 days, developed mechanical allodynia but had no changes in response to thermal stimuli. Administration of ddC increased the expression of mRNA of cytokines (interleukin 1 beta, tumor necrosis factor-alpha, and interferon-gamma), and the phosphorylated level of extracellular signal-regulated kinase p44/42 (ERK1/2). However, the administration of ddC did not alter the phosphorylated level of p38 mitogen-activated protein kinase (p38 MAPK) or the protein levels of the astrocytes and microglia markers: glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1), respectively. In addition, the administration of ddC did not alter the mRNA levels of Gfap but slightly downregulated the mRNA levels of another microglia marker: cluster of differentiation 11b (Cd11b), suggesting a lack of activation of brain microglia and astrocytes. Co-treatment with ddC and BCP, minocycline or pentoxifylline prevented the development of ddC-induced mechanical allodynia. In addition, BCP attenuated the established ddC-induced mechanical allodynia. The CB2 receptor antagonist AM 630, but not the CB1 receptor antagonist AM 251, blocked the antiallodynic effects of BCP. β-caryophyllene prevented the ddCinduced increase in cytokines mRNA, and the phosphorylated level of ERK1/2. In conclusion, BCP prevents NRTI-induced mechanical allodynia, possibly via reducing the inflammatory response, and attenuates mechanical allodynia through CB2 receptor activation. Therefore, BCP could be useful for the prevention and treatment of antiretroviral-induced neuropathic pain.
Appears in Programs:1100 Pharmaceutical Sciences

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