Nociceptive transmission to rat primary somatosensory cortex--comparison of sedative and analgesic effects

PLoS One. 2013;8(1):e53966. doi: 10.1371/journal.pone.0053966. Epub 2013 Jan 8.

Abstract

CO(2)-laser C-fibre evoked cortical potentials (LCEPs) is a potentially useful animal model for studies of pain mechanisms. A potential confounding factor when assessing analgesic effects of systemically administered drugs using LCEP is sedation. This study aims to clarify: 1) the relation between level of anaesthesia and magnitude of LCEP, 2) the effects of a sedative and an analgesic on LCEP and dominant EEG frequency 3) the effects of a sedative and analgesic on LCEP when dominant EEG frequency is kept stable. LCEP and EEG were recorded in isoflurane/nitrous-oxide anaesthetized rats. Increasing isoflurane level gradually reduced LCEPs and lowered dominant EEG frequencies. Systemic midazolam (10 μmol/kg) profoundly reduced LCEP (19% of control) and lowered dominant EEG frequency. Similarly, morphine 1 and 3 mg/kg reduced LCEP (39%, 12% of control, respectively) and decreased EEG frequency. When keeping the dominant EEG frequency stable, midazolam caused no significant change of LCEP. Under these premises, morphine at 3 mg/kg, but not 1 mg/kg, caused a significant LCEP reduction (26% of control). In conclusion, the present data indicate that the sedative effects should be accounted for when assessing the analgesic effects of drug. Furthermore, it is suggested that LCEP, given that changes in EEG induced by sedation are compensated for, can provide information about the analgesic properties of systemically administrated drugs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Electroencephalography
  • Evoked Potentials, Somatosensory / drug effects
  • Hypnotics and Sedatives / pharmacology*
  • Isoflurane / pharmacology
  • Male
  • Midazolam / pharmacology
  • Morphine / pharmacology
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / physiology
  • Nociception / drug effects*
  • Nociception / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Somatosensory Cortex / drug effects*
  • Somatosensory Cortex / physiology*
  • Synaptic Transmission / drug effects

Substances

  • Analgesics
  • Hypnotics and Sedatives
  • Morphine
  • Isoflurane
  • Midazolam

Grant support

This project was sponsored by Organon Inc (now Schering-Plough), a Linnaeus grant (project number: 60012701) from the Swedish Research Council and The Knut and Alice Wallenberg Foundation (project number: KAW 2004.0119). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.