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

J Pain Symptom Manage. 2017 Dec;54(6):815-825. doi: 10.1016/j.jpainsymman.2017.04.021. Epub 2017 Aug 8.

Abstract

Context: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Chemotherapy-induced peripheral neuropathy; chemotherapy-induced neuropathy; nerve growth factor; neuropathic pain; skin biopsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Bridged-Ring Compounds / adverse effects
  • Bridged-Ring Compounds / therapeutic use
  • Female
  • Humans
  • Leg / innervation
  • Leg / pathology
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Neoplasms / epidemiology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Nerve Growth Factor / blood*
  • Neural Conduction
  • Neuralgia / blood*
  • Neuralgia / chemically induced*
  • Neuralgia / epidemiology
  • Neuralgia / pathology
  • Pain Measurement
  • Platinum Compounds / adverse effects
  • Platinum Compounds / therapeutic use
  • Prospective Studies
  • Skin / drug effects
  • Skin / innervation
  • Skin / pathology
  • Surveys and Questionnaires
  • Taxoids / adverse effects
  • Taxoids / therapeutic use

Substances

  • Antineoplastic Agents
  • Bridged-Ring Compounds
  • NGF protein, human
  • Platinum Compounds
  • Taxoids
  • taxane
  • Nerve Growth Factor