Reactive Oxygen Species Donors Increase the Responsiveness of Dorsal Horn Neurons and Induce Mechanical Hyperalgesia in Rats.

Hee Young Kim,Inhyung Lee,Hee Kee Kim,Sang Woo Chun

doi:10.1155/2015/293423

Abstract

Our previous studies suggest that reactive oxygen species (ROS) scavengers have analgesic effect on neuropathic pain through spinal mechanisms in the rat. The studies suggest that superoxide in spinal cord is one of important mediators of persistent pain. To test the hypothesis that increase of superoxide-derived intermediates leads to central sensitization and pain, the effects of an intrathecal injection of chemical ROS donors releasing either OH∙, OCl−, or H2O2 were examined on pain behaviors. Following treatment with t-BOOH (OH∙ donor), dorsal horn neuron responses to mechanical stimuli in normal rats and the changes of neuronal excitability were explored on substantia gelatinosa (SG) neurons using whole-cell patch clamping recordings. Intrathecal administration of t-BOOH or NaOCl (OCl− donor), but not H2O2, significantly decreased mechanical thresholds of hind paws. The responses of wide dynamic range neurons to mechanical stimuli increased after a local application of t-BOOH. The t-BOOH increased the frequency and the amplitude of excitatory postsynaptic potentials, depolarized membrane potential in SG neurons, and increased the frequency of action potentials evoked by depolarizing current pulses. These results suggest that elevated ROS, especially OH∙, in the spinal cord sensitized dorsal horn neurons and produced hyperalgesia in normal rats.

Highlights

Reactive oxygen species (ROS) are generated as part of normal cell metabolism and serve both normal physiological and pathophysiological functions [1, 2]
This study showed that intrathecal administration of ROS donors t-BOOH and NaOCl but not H2O2 induced mechanical hyperalgesia of the hind paw in a dose-dependent manner in rats
In wholecell patch clamp recordings of spinal dorsal horn neurons, application of t-BOOH depolarized membrane potential and increased the frequency of action potential evoked by injection of a current

Summary

Introduction

Reactive oxygen species (ROS) are generated as part of normal cell metabolism and serve both normal physiological and pathophysiological functions [1, 2]. Include superoxide radicals (O2∙−), ), hydrogen peroxide (H2O2), nitric hydroxyl radicals oxide (NO), and peroxynitrite [2, 3]. Leakage of electrons during electron transport produces the superoxide anion (O2∙−), which transforms OH∙. ROS have been implicated in the pathogenesis of various diseases, including rheumatoid arthritis, asthma, inflammatory bowel disease, atherosclerosis, and Alzheimer disease. Previous studies suggested that ROS are critically involved in various pain conditions, including neuropathic and inflammatory pain. ROS scavengers such as superoxide dismutase mimetics [5], phenyl N-t-butylnitrone [6, 7], 5,5-dimethyl-1pyrroline-N-oxide [6], and vitamin E [8] reduce hyperalgesic behaviors in several rat models of pain.

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