The Roles of Superoxide on At-Level Spinal Cord Injury Pain in Rats.

Bong Hyo Lee,Jonghoon Kang,Hee Young Kim,Young S Gwak

doi:10.3390/ijms22052672

Bong Hyo Lee, Jonghoon Kang + Show 2 more

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https://doi.org/10.3390/ijms22052672

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Abstract

Background: In the present study, we examined superoxide-mediated excitatory nociceptive transmission on at-level neuropathic pain following spinal thoracic 10 contusion injury (SCI) in male Sprague Dawley rats. Methods: Mechanical sensitivity at body trunk, neuronal firing activity, and expression of superoxide marker/ionotropic glutamate receptors (iGluRs)/CamKII were measured in the T7/8 dorsal horn, respectively. Results: Topical treatment of superoxide donor t-BOOH (0.4 mg/kg) increased neuronal firing rates and pCamKII expression in the naïve group, whereas superoxide scavenger Tempol (1 mg/kg) and non-specific ROS scavenger PBN (3 mg/kg) decreased firing rates in the SCI group (* p < 0.05). SCI showed increases of iGluRs-mediated neuronal firing rates and pCamKII expression (* p < 0.05); however, t-BOOH treatment did not show significant changes in the naïve group. The mechanical sensitivity at the body trunk in the SCI group (6.2 ± 0.5) was attenuated by CamKII inhibitor KN-93 (50 μg, 3.9 ± 0.4) or Tempol (1 mg, 4 ± 0.4) treatment (* p < 0.05). In addition, the level of superoxide marker Dhet showed significant increase in SCI rats compared to the sham group (11.7 ± 1.7 vs. 6.6 ± 1.5, * p < 0.05). Conclusions: Superoxide and the pCamKII pathway contribute to chronic at-level neuropathic pain without involvement of iGluRs following SCI.

Highlights

Published: 6 March 2021Reactive oxygen species (ROS) are important substrates for excitatory nociceptive transmission in the spinal dorsal horn [1,2]
To determine whether superoxide contributes to thoracic dorsal horn neuronal hyperexcitability in naïve rats, we analyzed the firing rates of thoracic 7/8 wide dynamic range (T7/8 WDR) neurons in response to mechanical stimulation applied at the body trunk
To determine whether spinal thoracic contusion injury (SCI)-induced overproduction of ROS contributed to WDR neuronal hyperexcitability, the firing rates of WDR neurons in response to von Frey filament (VFF) stimuli were assessed in sham (11 neurons/4 rats), SCI + vehicle (13 neurons/13 rats), SCI + Tempol (8 neurons/8 rats, 1 mg/kg), and SCI + N-tert-butyl-α-phenylnitrone (PBN, 8 neurons/8 rats, 3 mg/kg) rats

Summary

Introduction

Published: 6 March 2021Reactive oxygen species (ROS) are important substrates for excitatory nociceptive transmission in the spinal dorsal horn [1,2]. ROS are generally produced by cellular metabolism, and the level of intracellular ROS is strictly controlled by the redox cycle via pro-oxidant and ROS scavengers [3,4,5] Neurotrauma, such as spinal cord injury (SCI), often results in the overproduction of ROS in the spinal dorsal horn followed by membrane and cellular physiological changes [6,7,8]. Methods: Mechanical sensitivity at body trunk, neuronal firing activity, and expression of superoxide marker/ionotropic glutamate receptors (iGluRs)/CamKII were measured in the T7/8 dorsal horn, respectively. SCI showed increases of iGluRs-mediated neuronal firing rates and pCamKII expression (* p < 0.05); t-BOOH treatment did not show significant changes in the naïve group.

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Conclusion