Open AccessComparison of chemotherapy effects on mechanical sensitivity and food-maintained operant responding in male and female rats
Author(s) -
Luke P Legakis,
Clare M Diester,
E. Andrew Townsend,
Ladan Karim-Nejad,
S. Stevens Negus
Publication year - 2019
Publication title -
behavioural pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 80
eISSN - 1473-5849
pISSN - 0955-8810
DOI - 10.1097/fbp.0000000000000527
Subject(s) - medicine , chemotherapy , neuropathic pain , bortezomib , paclitaxel , morphine , chemotherapy induced peripheral neuropathy , oxaliplatin , anesthesia , vincristine , peripheral neuropathy , pharmacology , cancer , endocrinology , cyclophosphamide , colorectal cancer , multiple myeloma , diabetes mellitus
Chemotherapies of varying classes often cause neuropathy and debilitating chemotherapy-induced neuropathic pain sufficient to limit treatment and reduce quality of life for many patients battling cancer. There are currently no effective preventive or alleviative treatments for chemotherapy-induced neuropathic pain. Preclinical models have been developed to test candidate chemotherapy-induced neuropathic pain treatments; however, studies using these models rarely provide direct comparisons of effects of different chemotherapies or assess the degree to which chemotherapies produce clinically relevant signs of pain-depressed behavior. Male and female Sprague-Dawley rats received four injections of vehicle, paclitaxel, oxaliplatin, vincristine, or bortezomib on alternate days. Mechanical hypersensitivity, body weight, and food-maintained operant responding were evaluated before, during, and for up to 42 days after initiation of treatment. Morphine potency and effectiveness to reverse chemotherapy-induced effects were also evaluated. All four chemotherapies produced dose-dependent and sustained mechanical hypersensitivity in all rats. Vincristine and oxaliplatin produced transient weight loss and decreases in food-maintained operant responding in all rats, whereas paclitaxel and bortezomib produced lesser or no effect. At 4 weeks after treatment, operant responding was depressed only in paclitaxel-treated males. Morphine reversed mechanical hypersensitivity in all rats but failed to reverse paclitaxel-induced depression of operant responding in males. We conclude that chemotherapy treatments sufficient to produce sustained mechanical hypersensitivity failed to produce sustained or morphine-reversible behavioral depression in rats. Insofar as pain-related behavioral depression is a cardinal sign of chemotherapy-induced neuropathic pain in humans, these results challenge the presumption that these chemotherapy-dosing regimens are sufficient to model clinically relevant chemotherapy-induced neuropathic pain in rats.