Chronic ibuprofen administration reduces neuropathic pain but does not exert neuroprotection after spinal cord injury in adult rats

Exp Neurol. 2014 Feb:252:95-103. doi: 10.1016/j.expneurol.2013.11.008. Epub 2013 Nov 15.

Abstract

Ibuprofen is commonly used as an anti-inflammatory analgesic drug, although it is not amongst the first-line treatments for neuropathic pain. Its main effects are mediated by non-specific inhibition of COX enzymes, but it also exerts some COX-independent effects, such as the inhibition of RhoA signaling and the modulation of glial activity. These effects have boosted the use of ibuprofen as a tool to promote axonal regeneration and to increase functional recovery after neural injuries, although with controversial results showing positive and negative outcomes of ibuprofen treatment in several experimental models. We have evaluated the effects of ibuprofen administered at 60 mg/kg twice a day to rats subjected to a mild spinal cord contusion. Our results indicate that ibuprofen ameliorates mechanical hyperalgesia in rats by reducing central hyperexcitability, but failed to produce improvements in the recovery of locomotion. Despite an early effect on reducing microglial reactivity, the ibuprofen treatment did not provide histological evidence of neuroprotection; indeed the volume of cord tissue spared rostral to the lesion was decreased in ibuprofen treated rats. In summary, the early modulation of neuroinflammation produced by the administration of ibuprofen seems to eventually lead to a worse resolution of detrimental events occurring in the secondary injury phase, but also to reduce the development of neuropathic pain.

Keywords: Functional recovery; Ibuprofen; Neuropathic pain; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Calcium-Binding Proteins / metabolism
  • Evoked Potentials, Motor / drug effects
  • Evoked Potentials, Somatosensory / drug effects
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Hyperalgesia / drug therapy
  • Ibuprofen / administration & dosage*
  • Locomotion / drug effects
  • Microfilament Proteins / metabolism
  • Neural Conduction / drug effects
  • Neuralgia / drug therapy*
  • Neuralgia / etiology*
  • Pain Measurement
  • Pain Threshold / drug effects
  • Psychomotor Performance / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reflex / drug effects
  • Spinal Cord Injuries / complications*

Substances

  • Aif1 protein, mouse
  • Anti-Inflammatory Agents, Non-Steroidal
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • Ibuprofen