Characterization of the sensory, affective, cognitive, biochemical, and neuronal alterations in a modified chronic constriction injury model of neuropathic pain in mice

J Neurosci Res. 2020 Feb;98(2):338-352. doi: 10.1002/jnr.24501. Epub 2019 Aug 8.

Abstract

The chronic constriction injury (CCI) of the sciatic nerve is a nerve injury-based model of neuropathic pain (NP). Comorbidities of NP such as depression, anxiety, and cognitive deficits are associated with a functional reorganization of the medial prefrontal cortex (mPFC). Here, we have employed an adapted model of CCI by placing one single loose ligature around the sciatic nerve in mice for investigating the alterations in sensory, motor, affective, and cognitive behavior and in electrophysiological and biochemical properties in the prelimbic division (PrL) of the mPFC. Our adapted model of CCI induced mechanical allodynia, motor, and cognitive impairments and anxiety- and depression-like behavior. In the PrL division of mPFC was observed an increase in GABA and a decrease in d-aspartate levels. Moreover an increase in the activity of neurons responding to mechanical stimulation with an excitation, mPFC (+), and a decrease in those responding with an inhibition, mPFC (-), was found. Altogether these findings demonstrate that a single ligature around the sciatic nerve was able to induce sensory, affective, cognitive, biochemical, and functional alterations already observed in other neuropathic pain models and it may be an appropriate and easily reproducible model for studying neuropathic pain mechanisms and treatments.

Keywords: GABA and d-aspartate levels; affective and cognitive behavior; chronic constriction injury; ongoing- and mechanically evoked neural activity; prelimbic division of the medial prefrontal cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartic Acid / metabolism*
  • Behavior, Animal / physiology*
  • Brain / metabolism
  • Brain / physiopathology
  • Cognition / physiology
  • Male
  • Mice
  • Neuralgia / etiology
  • Neuralgia / metabolism
  • Neuralgia / physiopathology*
  • Pain Measurement
  • Pain Threshold / physiology*
  • Peripheral Nerve Injuries / complications
  • Peripheral Nerve Injuries / metabolism
  • Peripheral Nerve Injuries / physiopathology*
  • Physical Stimulation
  • Sciatic Nerve / injuries*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Aspartic Acid
  • gamma-Aminobutyric Acid