title: A quantitative sensory analysis of peripheral neuropathy in colorectal cancer and its exacerbation by oxaliplatin chemotherapy.
abstract: Peripheral neuropathy caused by cytotoxic chemotherapy, especially platins and taxanes, is a widespread problem among cancer survivors that is likely to continue to expand in the future. However, little work to date has focused on understanding this challenge. The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight into the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing before and then prior to each cycle of oxaliplatin. These data were compared with those from 47 age- and sex-matched healthy volunteers. Patients showed significant subclinical deficits in sensory function before any therapy compared with healthy volunteers, and they became more pronounced in patients who received chemotherapy. Sensory modalities that involved large Aβ myelinated fibers and unmyelinated C fibers were most affected by chemotherapy, whereas sensory modalities conveyed by thinly myelinated Aδ fibers were less sensitive to chemotherapy. Patients with baseline sensory deficits went on to develop more symptom complaints during chemotherapy than those who had no baseline deficit. Patients who were tested again 6 to 12 months after chemotherapy presented with the most numbness and pain and also the most pronounced sensory deficits. Our results illuminate a mechanistic connection between the pattern of effects on sensory function and the nerve fiber types that appear to be most vulnerable to chemotherapy-induced toxicity, with implications for how to focus future work to ameloirate risks of peripheral neuropathy.
authors.affiliation: Faculdade de Ciências Médicas de Minas Gerais, Belo Horizonte, MG and CAPES/CNPq Coordination for the Improvement of Higher Education-Science without Borders, DF CNPJ, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: de Carvalho Barbosa
authors.affiliation: Department of Anesthesia and Pain Medicine Research, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Alyssa K
authors.initials: AK
authors.lastname: Kosturakis
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Cathy
authors.initials: C
authors.lastname: Eng
authors.affiliation: Department of Neurology, the University of Minnesota School of Medicine, Minneapolis, Minnesota.
authors.forename: Gwen
authors.initials: G
authors.lastname: Wendelschafer-Crabb
authors.affiliation: Department of Neurology, the University of Minnesota School of Medicine, Minneapolis, Minnesota.
authors.forename: William R
authors.initials: WR
authors.lastname: Kennedy
authors.affiliation: Department of Diagnostic and Biological Sciences, the University of Minnesota School of Dentistry, Minneapolis, Minnesota.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Simone
authors.affiliation: Department of Symptom Research, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Xin S
authors.initials: XS
authors.lastname: Wang
authors.affiliation: Department of Symptom Research, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cleeland
authors.affiliation: Department of Anesthesia and Pain Medicine Research, The University of Texas MD Anderson Cancer Center, Houston, Texas. pdougherty@mdanderson.org.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Dougherty
mesh_terms: D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D010146:Pain / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology*; D017741:Survivors
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin