Sympathetic Dependency of Cold-evoked Pain Behavior Seen in Rats with Peripheral Neuropathy

Choi, Byung Ock; Choi, Yoon; Gwak, Young Seob; Nam, Taick Sang; Paik, Kwang Se; Leem, Joong Woo

Abstract

BACKGROUND: Peripheral nerve injury sometimes leads to chronic neuropathic pain such as causalgia. A subset of patients with causalgia have a sympathetically maintained pain which is often evoked by cooling stimuli. However, our knowledge on adrenergic receptor types responsible for cold-evoked pain that is sympathetically dependent is lacking. The present study was conducted to investigate subtypes of adrenoceptors involved in mediating cold-evoked pain that developed following peripheral nerve injury.
METHODS
Neuropathic surgery was performed by a unilateral ligation of L5 and L6 spinal nerves of rats. Behavioral sign of cold-evoked pain was examined for 5 min by measuring cumulative duration of time that the rat lifted its foot off a metal plate held at cold temperature (5degrees C). Whether cold-evoked pain behavior was affected by antagonists of various subtypes of adrenoceptors, which were administered intraperitoneally before and after the ligation, was investigated.
RESULTS
After ligation, duration of foot lifting on the ligated side at cold temperature increased as compared to the pre-operative period. This increase maintained for the entire 40-day test period. Pretreatment with alpha-antagonist phentolamine produced a suppression of cold-evoked pain behavior that was not affected by beta-antagonist propranolol pretreatment. Prazosin, alpha-1 antagonist, suppressed cold- evoked pain behavior when treated either before or after nerve ligation. On the other hand, alpha-2 antagonist yohimbine was without effect on cold-evoked pain behavior whether it was treated before or after the ligation.
CONCLUSIONS
The results suggest that peripheral nerve injury develops cold-evoked pain that is sympathetically dependent, and that alpha-1 adrenoreceptor plays a critical role for the generation of this type of pain in its initiation as well as maintenance.