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.