Antinociceptive effect of intrathecal P7C3 via GABA in a rat model of inflammatory pain
Autor: | Han-Byul Kim, Yeo Ok Kim, Sang Wan Ryu, Myung Ha Yoon, Seog Bae Oh, Jeong Il Choi |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Pain Threshold medicine.drug_class Glutamate decarboxylase Carbazoles Pharmacology Nociceptive Pain Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Dorsal root ganglion Formaldehyde medicine Animals Calcium Signaling Injections Spinal gamma-Aminobutyric Acid Inflammation Analgesics GABAA receptor Glutamate Decarboxylase GABA receptor antagonist Bicuculline Receptor antagonist Disease Models Animal 030104 developmental biology medicine.anatomical_structure Nociception nervous system chemistry Spinal Cord Saclofen 030217 neurology & neurosurgery medicine.drug |
Zdroj: | European journal of pharmacology. 899 |
ISSN: | 1879-0712 |
Popis: | The recently identified molecule P7C3 has been highlighted in the field of pain research. We examined the effect of intrathecal P7C3 in tissue injury pain evoked by formalin injection and determined the role of the GABA system in the activity of P7C3 at the spinal level. Male Sprague-Dawley rats with intrathecal catheters implanted for experimental drug delivery were studied. The effects of intrathecal P7C3 and nicotinamide phosphoribosyltransferase (NAMPT) administered 10 min before the formalin injection were examined. Animals were pretreated with bicuculline, a GABA-A receptor antagonist; saclofen, a GABA-B receptor antagonist; L-allylglycine, a glutamic acid decarboxylase (GAD) blocker; and CHS 828, an NAMPT inhibitor; to observe involvement in the effects of P7C3. The effects of P7C3 alone and the mixture of P7C3 with GABA receptor antagonists on KCl-induced calcium transients were examined in rat dorsal root ganglion (DRG) neurons. The expression of GAD and the concentration of GABA in the spinal cord were evaluated. Intrathecal P7C3 and NAMPT produced an antinociceptive effect in the formalin test. Intrathecal bicuculline, saclofen, L-allylglycine, and CHS 828 reversed the antinociception of P7C3 in both phases. P7C3 decreased the KCl-induced calcium transients in DRG neurons. Both bicuculline and saclofen reversed the blocking effect of P7C3. The levels of GAD expression and GABA concentration decreased after formalin injection and were increased by P7C3. These results suggest that P7C3 increases GAD activity and then increases the GABA concentration in the spinal cord, which in turn may act on GABA receptors causing the antinociceptive effect against pain evoked by formalin injection. |
Databáze: | OpenAIRE |
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