Characterization of the effects of gabapentin and 3-isobutyl-gamma-aminobutyric acid on substance P-induced thermal hyperalgesia
| Autor: | Tony L. Yaksh, Brett J. Partridge, Sandra Reading Chaplan, Eiji Sakamoto |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
N-Methylaspartate Gabapentin Cyclohexanecarboxylic Acids Analgesic Substance P Pharmacology Acetates Aminobutyric acid gamma-Aminobutyric acid Rats Sprague-Dawley chemistry.chemical_compound Receptors GABA Serine Medicine Animals Amines gamma-Aminobutyric Acid Analgesics Behavior Animal Dose-Response Relationship Drug business.industry Stereoisomerism Rats Dose–response relationship Anesthesiology and Pain Medicine Mechanism of action chemistry Receptors Glutamate Hyperalgesia Anesthesia medicine.symptom business medicine.drug |
| Zdroj: | Anesthesiology. 88(1) |
| ISSN: | 0003-3022 |
| Popis: | Background The authors sought to characterize the pharmacologic characteristic and site of action of gabapentin (Neurontin) in a model of thermal hyperalgesia induced by intrathecal substance P administration. Methods Rats were prepared with long-term lumbar intrathecal catheters. Hind paw withdrawal latency was determined using a radiant heat stimulus focused through a glass surface onto the plantar surface of the paw. Results Within 5 min after intrathecal injection of substance P (30 nmol), hind paw withdrawal latency fell from 11 to 8 s. Gabapentin given intrathecally or intraperitoneally produced dose-dependent reversal of the thermal hyperalgesia, with complete reversal (ED100) occurring at 163 microg for intrathecal and 185 mg/kg for intraperitoneal administration. S(+)-3-isobutyl-gamma aminobutyric acid, but not R(-)-3-isobutyl-gamma aminobutyric acid, also produced dose-dependent reversal of the intrathecal substance P-induced thermal hyperalgesia (intrathecal ED100, 65 microg and intraperitonal ED100, 31 mg/kg). The effects of intraperitoneally administered gabapentin and 3-isobutyl-gamma aminobutyric acid were reversed by intrathecal pretreatment with D-serine (100 microg) but not by L-serine. All effects were observed at doses that had little effect on motor function or spontaneous activity. Intrathecal N-methyl-D-aspartate (2 nmol) induced thermal hyperalgesia, which was blocked by gabapentin (100 mg/kg intraperitoneally) and S(+)-3-isobutyl-gamma aminobutyric acid (30 mg/kg intraperitoneally). Conclusions The structure-activity relationship and the stereospecificity noted after intrathecal delivery suggest that gabapentin and S(+)-3-isobutyl-gamma aminobutyric acid act at a common spinal locus to modulate selectively a facilitated state of nociceptive processing. |
| Databáze: | OpenAIRE |
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