Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model

BACKGROUND: Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-D-aspartate (NMDA) receptors in the dorsal horn after an exogenous supply of three antioxidants in rats with chronic post-ischemia pain (CPIP). This serves as an animal model of complex regional pain syndrome type-I induced by hindpaw ischemia/reperfusion injury. METHODS: The application of tight-fitting O-rings for a period of three hours produced CPIP in male Sprague-Dawley rats. Allopurinol 4 mg/kg, allopurinol 40 mg/kg, superoxide dismutase (SOD) 4,000 U/kg, N-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg and SOD 4,000 U/kg plus L-NAME 10 mg/kg were administered intraperitoneally just after O-ring application and on the first and second days after reperfusion. Mechanical allodynia was measured, and activation of the NMDA receptor subunit 1 (pNR1) of the lumbar spinal cord (L4-L6) was analyzed by the Western blot three days after reperfusion. RESULTS: Allopurinol reduced mechanical allodynia and attenuated the enhancement of spinal pNR1 expression in CPIP rats. SOD and L-NAME also blocked spinal pNR1 in accordance with the reduced mechanical allodynia in rats with CPIP. CONCLUSION: The present data suggest the contribution of superoxide, produced via xanthine oxidase, and the participation of superoxide and nitric oxide as a precursor of peroxynitrite in NMDA mediated central sensitization. Finally, the findings support a therapeutic potential for the manipulation of superoxide and nitric oxide in ischemia/reperfusion related pain conditions.

Zoster Paresis Misconceived as a Radiculopathy due to Herniated Intervertebral Disc

Herpes zoster is a viral disease of the posterior root ganglion and sensory nerve fiber, which presents clinically with vesicular eruption of the skin, radicular pain and sensory changes in the distribution of the affected ganglion. However, involvement of the motor neurons can be seen as well. If classic cutaneous lesions are present, herpes zoster-related motor paresis is easily diagnosed. Otherwise, the diagnosis may be more difficult and suspicious, especially if weakness occurs as a symptom before cutaneous lesions appear, or abnormal findings on the MRI are consistent with the signs. There have been few reports of sciatica with motor loss preceding skin lesions. Here, we report a patient with herpes zoster-related motor paresis preceding skin lesions. In the preliminary diagnosis, the herpes zoster-related motor paresis was confused for some structural disorder.

Reactive oxygen species and N-methyl-D-aspartate receptor-mediated central sensitization in hindlimb ischemia/reperfusion injury-induced neuropathic pain rats / 대한마취과학회지

BACKGROUND: Reactive oxygen species (ROS) contribute to development of neuropathic pain. A neuropathic pain syndrome was produced in rats following prolonged hindpaw ischemia/reperfusion injury, creating an animal model of complex regional pain syndrome-Type I (CRPS-I). This study was designed to evaluate the validity of this model for ROS and pain research. Herein we show superoxide produces N-methyl-D-aspartate (NMDA) mediated mechanical allodynia. METHODS: Male adult SD rats were used for neuropathic pain model. Plasma superoxide production rates of before ischemia (BI) and 5 min after reperfusion (JR) were measured via cytochrome C reduction in the presence of xanthine (without xanthine oxidase, kinetics, 550 nm). Mechanical allodynia was measured in both hindpaws. Activation of NMDA receptor subunit 1 (P-NR1) of lumbar spinal cord (L4-L6) in accordance with the change of allodynia was analyzed by the Western blot. RESULTS: Allopurinol-inhibitable, xanthine oxidase-mediated plasma superoxide production was increased at AR. Mechanical allodynia was present in both hindpaws as early as 1 hr after reperfusion, and lasted at least 1 week. The expression of P-NR1 was the highest at 3 days after reperfusion when the withdrawal threshold was the lowest point. SOD significantly blocked P-NR1 activation. CONCLUSIONS: This study suggests that ischemia/reperfusion injury induced neuropathic pain model is a good candidate for the research fields of ROS and pain mechanism. The generation of ROS, especially superoxide is partly responsible for NMDA-mediated mechanical allodynia.