Pain behavior and response properties of spinal dorsal horn neurons following experimental diabetic neuropathy in the rat: modulation by nitecapone, a COMT inhibitor with antioxidant properties

Exp Neurol. 2001 Feb;167(2):425-34. doi: 10.1006/exnr.2000.7574.

Abstract

We attempted to characterize a spinal neuronal correlate of painful neuropathy induced by diabetes mellitus (DM). Pain behavior and response properties of spinal dorsal horn neurons were determined in rats with a streptozocin-induced DM. A catechol-O-methyltransferase inhibitor with potent antioxidant properties, nitecapone, was used in an attempt to attenuate neuropathic symptoms. Behaviorally DM induced mechanical hypersensitivity that was markedly attenuated by oral treatment with nitecapone. The antihyperalgesic effect of nitecapone was not reversed by naloxone, an opioid antagonist, or atipamezole, an alpha-2-adrenoceptor antagonist. Electrophysiological recordings performed in pentobarbitone-anesthetized animals revealed that the most distinct abnormality in response properties of spinal dorsal horn wide-dynamic range (WDR) neurons was the increase in their spontaneous activity observed in untreated but not in nitecapone-treated DM rats. Conditioning electrical stimulation and a lidocaine block of the rostroventromedial medulla (RVM) had a similar modulatory effect on evoked responses of spinal dorsal horn WDR neurons in all experimental groups. The response properties of spinal dorsal horn nociceptive-specific or low-threshold mechanoreceptive neurons were not markedly different between the experimental groups. The results indicate that increased spontaneous activity in spinal dorsal horn WDR neurons may be causally related to behaviorally observed mechanical hypersensitivity in DM. Attenuation of the increased spontaneous activity in WDR neurons may explain the antihyperalgesic effect by nitecapone, due to naloxone- and alpha-2-adrenoceptor-insensitive mechanisms. DM or nitecapone treatment did not produce significant changes in phasic or tonic descending pain regulation originating in the RVM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-2 Receptor Antagonists
  • Analysis of Variance
  • Anesthetics, Local / pharmacology
  • Animals
  • Antioxidants / administration & dosage
  • Behavior, Animal / drug effects
  • Catechol O-Methyltransferase Inhibitors
  • Catechols / administration & dosage*
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / etiology
  • Diabetic Neuropathies / pathology
  • Electric Stimulation
  • Enzyme Inhibitors / administration & dosage
  • Lidocaine / pharmacology
  • Male
  • Membrane Potentials / drug effects
  • Narcotic Antagonists / pharmacology
  • Pain Measurement / drug effects
  • Pentanones / administration & dosage*
  • Posterior Horn Cells / drug effects*
  • Posterior Horn Cells / pathology
  • Posterior Horn Cells / physiopathology*
  • Rats
  • Rats, Wistar
  • Sensory Thresholds

Substances

  • Adrenergic alpha-2 Receptor Antagonists
  • Anesthetics, Local
  • Antioxidants
  • Catechol O-Methyltransferase Inhibitors
  • Catechols
  • Enzyme Inhibitors
  • Narcotic Antagonists
  • Pentanones
  • nitecapone
  • Lidocaine