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 / 대한마취과학회지

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.

The Analgesic Effect of Intrathecal Gabapentin in a Rat Model of Incisional Pain / 대한마취과학회지

BACKGROUND: Gabapentin, an anticonvulsant structurally related to gamma-aminobutyric acid (GABA), was recently reported to be effective in pain associated with reflex sympathetic dystrophy and neuropathy. However, the effects of intrathecal (IT) gabapentin in postoperative pain are unclear. This study was designed to evaluate the analgesic action of IT gabapentin in a rat model of postoperative pain which was similar to human postoperative pain states. METHODS: Rats were prepared with chronic intrathecal catheter. Under halothane anesthesia, a 1 cm incision was made in the plantar aspect of the hind paw and closed. Rats were divided into 7 groups, a control group (saline 20 microliter intrathecally n = 6); a GP 30 group (gabapentin 30 microgram intrathecally, n = 6); a GP 100 group (gabapentin 100 microgram intrathecally, n = 6); a GP 300 group (gabapentin 300 microgram intrathecally, n = 6); a GP 1000 group (gabapentin 1,000 microgram intrathecally, n = 6); a NS-GP group (saline 10 microliter and gabapentin 300 microgram intrathecally, n = 6) and DS-GP group (D-serine 100 microgram and gabapentin 300 microgram intrathecally, n = 6). The rats were placed on an elevated plastic mesh floor, and withdrawal threshold was determined using calibrated von Frey filaments applied from beneath the test cage to an area adjacent to the wound. A cumulative pain score based on the weight bearing behavior of the rats, and motor deficit score, were also assessed. RESULTS: In all group, the median withdrawal threshold for punctate hyperalgesia decreased from 148.4 mN before surgery to 1.5 mN-14.5 mN 2 hours after surgery-inducing hyperalgesia and remained unchanged during the 2hr testing period. The IT administration of gabapentin (30 300 microgram) increased the median withdrawal threshold toward preincision values dose-dependently and the nonevoked pain scores were also decreased. But the effects of intrathecal gabapentin were reversed by IT D-serine. The Analgegic effects of gabapentin were observed at doses that had no significant effect on motor function or spontaneous activity. CONCLUSIONS: These observations suggest that intrathecal gabapentin can modulate the facilitation of spinal nociceptive processing by tissue injury and may offer a therapeutic agent for the treatment of postoperative pain.