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

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 naive 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 naive group. The mechanical sensitivity at the body trunk in the SCI group (6.2 +/- 0.5) was attenuated by CamKII inhibitor KN-93 (50 mu g, 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.

Automated summary

The study investigated superoxide-mediated excitatory nociceptive transmission in at-level neuropathic pain following SCI in male Sprague Dawley rats. Results showed that SCI led to increased iGluRs-mediated neuronal firing rates and pCamKII expression, while t-BOOH treatment did not have significant effects. Mechanical sensitivity at the body trunk in the SCI group was attenuated by CamKII inhibitor KN-93 or Tempol treatment, and the level of superoxide marker Dhet was significantly increased in SCI rats.