Ibudilast reduces oxaliplatin-induced tactile allodynia and cognitive impairments in rats

Behav Brain Res. 2017 Sep 15:334:109-118. doi: 10.1016/j.bbr.2017.07.021. Epub 2017 Jul 21.

Abstract

Chemotherapy can cause serious neurotoxic side effects, such as painful peripheral neuropathies and disabling cognitive impairments. Four experiments examined whether Ibudilast, a clinically approved neuroimmune therapy, would reduce tactile allodynia and memory impairments caused by oxaliplatin in laboratory rats. Rats received an intraperitoneal injection of oxaliplatin (6mg/kg i.p.) or vehicle and were assessed for tactile allodynia 3 or 5days after injection, memory impairments in the novel object and novel location recognition tests 10-12days after injection, and fear conditioning 14days after injection. Ibudilast (7.5mg/kg) or vehicle was administered prior to oxaliplatin (Experiments 1 and 3) or prior to behavioural testing (Experiments 2 and 4). Ibudilast treatment prior to oxaliplatin prevented the development of tactile allodynia and memory impairments. Ibudilast treatment prior to behavioural testing reduced oxaliplatin-induced tactile allodynia, memory impairments, and impaired renewal of fear conditioning. These results suggest that Ibudilast could be an effective treatment against oxaliplatin-induced neuropathies and cognitive impairments.

Keywords: Chemotherapy; Ibudilast; Memory impairment; Neuropathic pain; Oxaliplatin.

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Antineoplastic Agents / toxicity
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / drug therapy*
  • Conditioning, Psychological / drug effects
  • Fear / drug effects
  • Female
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy
  • Nootropic Agents / pharmacology*
  • Organoplatinum Compounds / toxicity*
  • Oxaliplatin
  • Pyridines / pharmacology*
  • Rats, Wistar
  • Recognition, Psychology / drug effects
  • Space Perception / drug effects
  • Touch

Substances

  • Analgesics
  • Antineoplastic Agents
  • Nootropic Agents
  • Organoplatinum Compounds
  • Pyridines
  • Oxaliplatin
  • ibudilast