The Role of Steroids and Their Effects on Phospholipase A2: An Animal Model of Radiculopathy

Abstract

STUDY DESIGN: The possible role of phospholipase A2 in an animal model for lumbar radiculopathy and mechanisms of epidural steroid injections were studied. OBJECTIVES: To clarify the pathophysiologic mechanism of the recently proved animal model for lumbar radiculopathy and to characterize further the mechanisms of action of steroids. SUMMARY OF BACKGROUND DATA: There have been several reported animal models of peripheral neuropathy. Recently an animal model that shows reliable behavioral and neurochemical changes was proposed, and epidural steroid injections in this model were effective in the reduction of thermal hyperalgesia and allodynia. METHOD: In a behavioral study, 24 rats were divided into 4 groups: Group I, loose ligature of the left L4 and L5 nerve roots with 4-0 chromic gut sutures and an epidural injection of 0.1 mL of saline at 3 days after surgery; Group II, same as Group I but with an epidural injection of 0.1 mL of betamethasone on the day before the operation; Group II, same as Group II except injection at 1 day after surgery; Group IV, same as Group II except injection at 3 days after surgery. To test the phospholipase A2 activity in the nerve roots and dorsal root ganglia after the operation, eight rats were killed at given intervals. Analysis of variance techniques were used to test behavioral pattern changes and phospholipase A2 activity across time in each group. RESULTS: Thermal hyperalgesia reached its maximal point at 3 weeks after surgery in Group I, but in steroid injection groups, the recovery from hyperalgesia was faster than in Group I. However, there was no significant difference in recovery time among steroid injection groups. The level of phospholipase A2 activity was at its maximum at 1 week after surgery in Groups I and IV. It showed a steady reduction in the steroid group, whereas it remained relatively high and dropped rapidly after 3 weeks in the saline-treated group, and returned to the level of a normal nerve root at 6 weeks after surgery. CONCLUSION: These results suggest that the behavioral pattern changes observed in the irritated nerve root model are caused in part by a high level of phospholipase A2 activity initiated by inflammation, and that the mechanism of action of epidural steroid injection in this model is inhibition of phospholipase A2 activity.