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Pain attenuating actions of vincristinet‐preconditioning in chemotherapeutic agent‐induced neuropathic pain: key involvement of T‐type calcium channels
Author(s) -
Sharma Jasmine,
Maslov Leonid N.,
Singh Nirmal,
Jaggi Amteshwar Singh
Publication year - 2020
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12519
Subject(s) - vincristine , pharmacology , neuropathic pain , medicine , amlodipine , calcium channel , calcium channel blocker , anesthesia , ethosuximide , calcium , chemotherapy , phenytoin , cyclophosphamide , psychiatry , blood pressure , epilepsy
Preconditioning is a well‐documented strategy that induces hepatic protection, renal protection, cardioprotection, and neuroprotection but its mechanism still remains to be elucidated. Hence, the present study investigated the protective mechanism underlying pain attenuating effects of vincristine‐preconditioning in chemotherapeutic agent‐induced neuropathic pain. Neuropathic pain was induced by administration of vincristine (50 µg/kg, i.p.) for 10 days in rats. Vincristine‐preconditioning was induced by administration of vincristine (2, 5, and 10 µg/kg, i.p) for 5 days before administration of pain‐inducing dose of vincristine (50 µg/kg, i.p.). Vincristine‐preconditioning (10 µg/kg, i.p) for 5 days significantly reduced vincristine (50 µg/kg, i.p.) induced pain‐related behaviors including paw cold allodynia, mechanical hyperalgesia, and heat hyperalgesia. However, vincristine (2 and 5 µg/kg, i.p) did not significantly ameliorate the vincristine (50 µg/kg, i.p.) induced neuropathic pain in rats. Furthermore, to explore the involvement of calcium channels in pain attenuating mechanism of vincristine‐preconditioning, T‐type calcium channel blocker, ethosuximide (100 and 200 mg/kg, i.p.) and L‐type calcium channel blocker, amlodipine (5 and 10 mg/kg, i.p.) were used. Pretreatment with T‐type calcium channel blocker, ethosuximide significantly abolished vincristine‐preconditioning‐induced protective effect. However, pretreatment with L‐type calcium channel blocker, amlodipine did not alter vincristine‐preconditioning‐induced pain‐related behaviors. This indicates that vincristine‐preconditioning has protective effect on pain‐related parameters due to opening of calcium channels, particularly T‐type calcium channels that lead to entry of small magnitude of intracellular calcium through these channels and prevent the deleterious effects of high‐dose vincristine.