Oxaliplatin treatment changes the function of sensory nerves in rats

J Pharmacol Sci. 2016 Apr;130(4):189-93. doi: 10.1016/j.jphs.2015.12.004. Epub 2015 Dec 17.

Abstract

Oxaliplatin (L-OHP) is a platinum-based chemotherapy drug, used in standard treatment of colorectal cancer. L-OHP frequently causes acute peripheral neuropathies. These adverse effects limit cancer therapy with L-OHP. The present study was designed to reveal the changes in sensory nerve function in L-OHP-injected rats. Mechanical static allodynia, dynamic allodynia, and cold allodynia were evaluated using the von Frey test, brush test, and acetone test, respectively. Sensory nerve fiber responsiveness was measured using a Neurometer. The fifth lumbar ventral root was sectioned to record multi-unit efferent discharges. Single intraperitoneal administration of L-OHP induced mechanical static allodynia, dynamic allodynia, and cold allodynia in Wistar/ST rats. The thresholds for paw withdrawal induced by 2000 Hz (Aβ-fiber) and 5 Hz (C-fiber), but not 250 Hz (Aδ-fiber) sine-wave electrical stimulation were reduced in L-OHP-treated rats. Multi-unit efferent discharges were increased by mechanical stimulation using a von Frey filament applied to the plantar surface of the hindpaw. The discharges during and after stimulation were increased in the L-OHP-treated rats. Cold stimulation, but not brush stimulation, increased the discharges in L-OHP-treated rats. These results suggest that sensitization of Aβ- and C-fibers, but not Aδ-fibers, contributes to the development of L-OHP-induced mechanical and cold allodynia.

Keywords: Efferent discharge; Neurometer; Neuropathic pain; Oxaliplatin (L-OHP); Sensory nerve.

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Hyperalgesia / chemically induced
  • Hyperalgesia / physiopathology
  • Male
  • Nerve Fibers / drug effects
  • Nerve Fibers / physiology
  • Nociception / drug effects
  • Nociception / physiology
  • Organoplatinum Compounds / adverse effects*
  • Oxaliplatin
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / physiopathology
  • Physical Stimulation
  • Rats, Wistar
  • Sensory Receptor Cells / drug effects*
  • Sensory Receptor Cells / physiology*
  • Spinal Cord / physiology

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin