Yeo Ok Kima, 1,  In Ji Kima, 1, Myung Ha Yoona, b, ,
a Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, South Korea

b Center for Creative Biomedical Scientists at Chonnam National University, Gwangju, South Korea

DOI: 10.1016/j.neulet.2014.10.005

Highlights

• Each CRPS-I and -II rat model was made by O-ring application or by spinal nerve ligation.
• The level of ET-1 in the spinal cord was increased in both CRPS models.
• Intrathecal ET-B receptor antagonist increased the withdrawal threshold in both CRPS types.
• Intrathecal ET-A receptor antagonist did not affect the withdrawal threshold in either CRPS type.
• Intrathecal ET-B receptor antagonist decreased the spinal ET-1 level in both CRPS rats.

Abstract

Complex regional pain syndrome (CRPS) is a very complicated chronic pain disorder that has been classified into two types (I and II). Endothelin (ET) receptors are involved in pain conditions at the spinal level. We investigated the role of spinal ET receptors in CRPS. Chronic post-ischemia pain (CPIP) was induced in male Sprague–Dawley rats as a model for CRPS-I by placing a tourniquet (O-ring) at the ankle joint for 3 h, and removing it to allow reperfusion. Ligation of L5 and L6 spinal nerves to induce neuropathic pain was performed as a model for CRPS-II. After O-ring application and spinal nerve ligation, the paw withdrawal threshold was significantly decreased at injured sites. Intrathecal administration of the selective ET-B receptor antagonist BQ 788 dose-dependently increased the withdrawal threshold in both CRPS-I and CRPS-II. In contrast, ET-A receptor antagonist BQ 123 did not affect the withdrawal threshold in either CRPS type. The ET-1 levels of plasma and spinal cord increased in both CRPS types. Intrathecal BQ 788 decreased the spinal ET-1 level. These results suggest that ET-1 is involved in the development of mechanical allodynia in CRPS. Furthermore, the ET-B receptor appears to be involved in spinal cord-related CRPS