The Effect of Intrathecal ACEA 1021, Competitive Glycine-site NMDA Receptor Antagonist on the Hyperalgesia Observed after Thermal Injury in the Rat / 대한마취과학회지

BACKGROUND: Previous reports have described NMDA antagonist reduced the nerve injury induced or inflammatory thermal hyperalgesia. One of the peculiarities of the NMDA receptor is the requirement for glycine as the co-agonist in order to be activated. Thus, the function of NMDA receptors can be modulated by ligands acting as agonists or antagonists at the glycine co-agonist site. ACEA 1021 has been recently characterized as a high potency competitive NMDA receptor/glycine site antagonist. This study evaluated the effects of spinally administered ACEA 1021 on the thermal hyperalgesia state induced by mild burn. METHODS: Rats were prepared with chronic spinal catheters. A thermal injury was induced after briefly anesthetizing with halothane, by applying the left hind paw to a thermal surface (52.5oC) for 45 sec. This exposure results in a mild erythema, but no blistering. Thermal escape latency of the hind paw was determined using an underglass thermal stimulus with which response latencies of the injured and uninjured (normal) paw could be obtained. In this work, ACEA 1021 was injected through intrathecal catheters in rats with mild burn injury on the right hindpaw, after then paw withdrawal latency was measured in both hindpaw every 30 minute for 3 hours. RESULTS: The intrathecal injection of ACEA 1021 (2.4-24 microgram) produced a dose dependent reversal of the hyperalgesia in the right hindpaw, but had no effect upon the response latency of the normal left hind paw even at the largest doses. The effects of intrathecal ACEA 1021 on the hyperalgesia reversed by intrathecal D-serine. CONCLUSIONS: Intrathecal ACEA 1021, competitive-glycine site NMDA receptor antagonist produce a dose-dependent inhibition and D-serine-sensitive reversal of the thermal hyperalgesia evoked mild burn injury. These results suggested that the glycine site of spinal NMDA receptor play an important role in the hyperalgesia induced by mild burn injury.

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.

The Effect of Intrathecal NMDA and non-NMDA Receptor Antagonist on the Hyperalgesia Observed after Thermal Injury in the Rat / 대한마취과학회지

BACKGROUND: Previous reports have described NMDA antagonist reduced the nerve injury induced or inflammatory thermal hyperalgesia. This study evaluated the effects of spinally administered excitatory amino acid antagonists on the thermal hyperalgesia state induced by mild burn. METHODS: The measured response was the latency to paw withdrawal of each hindpaw after application of a focused heat lamp on the plantar surface of the paw through a glass plate upon which the animal stood. In this work, MK801, non-competitive NMDA receptor antagonist, AP5, competitive NMDA receptor antagonist, CNQX, non-NMDA receptor antagonist were injected through chronically implanted lumbar intrathecal catheters in rats with mild burn injury on the right hindpaw. RESULTS: In the normal left hindpaw, MK801, AP5 and CNQX had little effect upon paw withdrawal latency (PWL) at intrathecal doses which do not produce readily detectable motor weakness. In the right hyperalgesic hindpaw, AP5 significantly reduced PWL at a dose-dependent fashion, MK801 reduced PWL to some extent, and CNQX did not reduced PWL. CONCLUSIONS: These results suggested that spinal NMDA receptors play an important role in the hyperalgesia induced by mild burn injury.