Effects of antidepressant agents on the neuropathic pain induced by oxaliplatin / 中国癌症杂志

ABSTRACT

Background and purpose:Oxaliplatin is a new cytotoxic platinum compound widely used in antineoplastic treatments.Peripheral neuropathy characterized by allodynia remains the most common way to limit the usage of oxaliplatin.Oxaliplatin-associated neuropathic pain is often resistant to standard analgesics.The effects of antidepressant agents such as desipramine and fluoxetine on chemotherapy-induced neuropathic pain were investigated so as to provide experimental evidence for clinical treatment.Methods:A single injection of oxaliplatin(30 mg/kg)intraperitoneal was injected into a test subject,a mouse that had chronic neuropathic pain.Using the von Frey filament as a touch stimulator,the mechanical withdrawal threshold(MWT)was measured when observing allodynia.The MWT was measured before and 1 h after the administration of desipramin and fluoxetine.Results:Desipramine and fluoxetine both have the potential to increase the MWT in mice with oxaliplatin-induced neuropathic pain.Pretreatment with antagonists such as an opioid receptor like naloxone could deepen their effects.Furthermore,when desipramine is combined with an opioid analgesic as buprenorphine,it causes an augmentation in the MWT.Conclusion:Antidepressants desipramine and fluoxetine antagonize oxaliplatin-induced neuropathic pain by inhibiting allodynia.Furthermore,the tricyclic antidepressing agent desipramine could enhance the effects of buprenorphine in subjects with oxaliplatin-induced pain,suggesting a synergistic effect for opioid analgesic.