Effects of Substance P Antagonist, [D-Arg, D-Phe, D-Trp, Leu]- Substance P on the Mechanical Hyperalgesia of Inflammation Induced by Freund's Complete Adjuvant in Rat Paw

Kim, Min Kyung; Choi, Yoon; Kong, Hyun Seok; Leem, Joong Woo; Yang, Hyun Cheol; Chung, Soo Jin; Hwang, Seung Jun; Hwang, Jai Hyun

Abstract

BACKGROUND: The effect of substance P (SP) on the hyperalgesia induced by inflammation is controversial, and as SP remains in the periphery just for a short period of time after release from the nerve ending, the contribution of SP on the development of sustained mechanical hyperalgesia in rats with inflammation is questionable. The purpose of this experiment is to evaluate the effect of SP on the development of mechanical hyperalgesia induced by Freund's complete adjuvant (FCA) using SP antagonist [D-Arg, D-Phe, D-Trp, Leu]-substance P (SPA).
METHODS
Male Sprague Dawley rats were divided into four groups; control (normal saline) and three different doses of SPA (0.25 microgram, 2.5 microgram, 25 microgram/0.1 ml). Inflammation was induced in rats by injecting 0.15 ml of FCA intraplantarly. Rats showed typical hyperalgesia within 12 hours after injection and maintained it for about one week. To test the effect of SPA on the developement of inflammation, either SPA or saline was injected at 1 h before and at the time of FCA injection under light halothane anesthesia after a baseline test. The effect of SPA on hyperalgesia was assessed by measuring mechanical hyperalgesia at 2, 6, 12, 24 hrs and 4 days after injection of the drug. To test the effect of SPA on fully developed inflammation, tests were done 2 days after injection of FCA. Mechanical hyperalgesias were assessed at 15, 30, 60, 90, 120 min after the drug injections.
RESULTS
SPA injected to suppress the initial SP spill over decreased the mechanical hyperalgesia in a dose dependent manner. SPA injected after the full development of inflammation also decreased mechanical hyperalgesia.
CONCLUSIONS
SP released at the initial phase of inflammation as well as SP released after the development of inflammation are all important for the maintainance of mechanical hyperalgesia.