Neuropathic Pain and Nerve Growth Factor in Chemotherapy-Induced Peripheral Neuropathy: Prospective Clinical-Pathological Study.

Abstract

Neuropathic pain can be present in patients developing chemotherapy-induced peripheral neuropathy (CIPN). Nerve growth factor (NGF) is trophic to small sensory fibers and regulates nociception. We investigated the changes in serum NGF and intraepidermal nerve fiber density in skin biopsies of cancer patients receiving neurotoxic chemotherapy in a single-center prospective observational study. Patients were evaluated before and after chemotherapy administration. CIPN was graded with Total Neuropathy Score^©, nerve conduction studies, and National Common Institute-Common Toxicity Criteria for Adverse Events scale. Neuropathic pain was defined according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN20 questionnaire. Neuropathic pain was present in 13 of 60 patients (21%), who reported shooting or burning pain in the hands (n = 9) and the feet (n = 12). Patients displaying painful CIPN presented higher NGF after treatment compared with patients with painless or absent CIPN (8.7 ± 11.9 vs. 2.5 ± 1.4 pg/mL, P = 0.016). The change of NGF significantly correlated with neuropathic pain. Patients with painful CIPN did not show significant loss of IEFND compared with patients with painless or absent CIPN (6.16 ± 3.86 vs. 8.37 ± 4.82, P = 0.12). No correlation between IEFND and NGF was observed. Serum NGF increases in cancer patients receiving taxane or platinum with painful CIPN, suggesting that it might be a potential biomarker of the presence and severity of neuropathic pain in this population. Long-term comprehensive studies to better define the course of NGF in relation with neurological outcomes would be helpful in the further design of therapies for CIPN-related neuropathic pain.