title: Altered discharges of spinal neurons parallel the behavioral phenotype shown by rats with bortezomib related chemotherapy induced peripheral neuropathy.
abstract: Bortezomib is a first generation proteasome inhibitor that is the frontline chemotherapy for multiple myeloma with the chief dose-limiting side effect of painful peripheral neuropathy. The goal of this study was to define the behavioral phenotype in a preclinical model of bortezomib chemotherapy-induced peripheral neuropathy (CIPN) and to test whether this is matched by changes in the physiological responses of spinal wide dynamic range neurons. Sprague-Dawley rats were treated with four injections of bortezomib at four doses, 0.05mg/kg, 0.10mg/kg, 0.15mg/kg, 0.20mg/kg, or equal volume of saline. All doses of bortezomib above 0.05mg/kg produced showed significant dose-dependent mechanical hyperalgesia that was fully established at 30 days after treatment and that recovered to baseline levels by day 69 after treatment. Thermal, cold, and motor testing were all unaffected by treatment with bortezomib. Spinal wide dynamic range (WDR) neurons in rats with confirmed bortzomib-related CIPN showed an increase in number of evoked discharges to mechanical stimuli and exaggerated after-discharges in rats with bortezomib CIPN.
authors.affiliation: Department of Anesthesia and Pain Medicine Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Caleb R
authors.initials: CR
authors.lastname: Robinson
authors.affiliation: Department of Anesthesia and Pain Medicine Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia and Pain Medicine Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: pdougherty@mdanderson.org.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Dougherty
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001897:Boronic Acids / Q000009:adverse effects*; D000069286:Bortezomib; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D008159:Lumbar Vertebrae; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D010812:Physical Stimulation; D011719:Pyrazines / Q000009:adverse effects*; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D013696:Temperature; D014110:Touch
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib
keywords: Bortezomib; Chemotherapy-induced peripheral neuropathy; Wide dynamic range neurons