Inflammatory pain in the rabbit: A new, efficient method for measuring mechanical hyperalgesia in the hind paw
| Autor: | Xiao Ding, Jian J. Chen, Eileen Johnson, Hong Dong, Hong Sun, Gondi N. Kumar, Barton H. Manning, Ella Magal |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Pain Threshold
Time Factors Hydrocarbons Fluorinated Indomethacin Analgesic Pain Bradykinin Pharmacology Carrageenan chemistry.chemical_compound Reaction Time medicine Animals Drug Interactions Receptor Pain Measurement Inflammation Analysis of Variance Dose-Response Relationship Drug Chemistry Spectrum Analysis General Neuroscience Anti-Inflammatory Agents Non-Steroidal Antagonist Kallidin Nociception Opioid Hyperalgesia Morphine Rabbits Metacarpus medicine.symptom Ethers medicine.drug |
| Zdroj: | Journal of Neuroscience Methods. 168:76-87 |
| ISSN: | 0165-0270 |
| Popis: | The discovery of novel analgesic compounds that target some receptors can be challenging due to species differences in ligand pharmacology. If a putative analgesic compound has markedly lower affinity for rodent versus other mammalian orthologs of a receptor, the evaluation of antinociceptive efficacy in non-rodent species becomes necessary. Here, we describe a new, efficient method for measuring inflammation-associated nociception in conscious rabbits. An electronic von Frey device is used, consisting of a rigid plastic tip connected to a force transducer in a hand-held probe. The plastic tip is applied to the plantar surface of a hind paw with increasing force until a withdrawal response is observed. The maximum force (g) tolerated by the rabbit (i.e., withdrawal threshold) is recorded. In young, conscious rabbits (500-700 g), baseline hind paw withdrawal thresholds typically fell within the 60-80 g range. Three hours after injection of the inflammatory agent carrageenan (3%, 200 microL, intra-plantar), withdrawal thresholds dropped by approximately 30-40 g, indicating the presence of punctate mechanical hyperalgesia. The development of hyperalgesia was dose dependently prevented by the NSAID indomethacin (ED50=2.56 mg/kg, p.o.) or the bradykinin B2 receptor peptide antagonist HOE 140 (intra-paw administration). An established hyperalgesia was dose dependently reversed by morphine sulfate (ED50=0.096 mg/kg, s.c.) or the bradykinin B1 receptor peptide antagonist [des-Arg10, Leu9]-kallidin (ED50=0.45 mg/kg, s.c.). Rabbits treated with the novel B(1) receptor small molecule antagonist compound A also showed dose-dependent reversal of hyperalgesia (ED50=20.19 mg/kg, s.c.) and analysis of plasma samples taken from these rabbits showed that, unlike other rabbit pain models, the current method permits the evaluation of pharmacokinetic-pharmacodynamic (PK-PD) relationships (compound A plasma EC50=402.6 nM). We conclude that the Electrovonfrey method can be used in rabbits with inflammatory pain to generate reliable dose- and plasma concentration-effect curves for different classes of analgesics. |
| Databáze: | OpenAIRE |
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