Prevention of electrical stimulation-induced increase of c-fos immunoreaction in the caudal trigeminal nucleus by kynurenine combined with probenecid.
The systemic administration of nitroglycerine, regarded as a migraine model, was previously observed to result in an increased number of c-fos immunoreactive secondary sensory neurons in the caudal trigeminal nucleus, which forward nociceptive impulses to the thalamus. The present investigation tested the hypothesis of whether kynurenine in combination with systemically administered probenecid protects second-order trigeminal neurons against stimulation arriving via central processes of trigeminal ganglion cells. Electrical stimulation of the trigeminal ganglion, one of the experimental migraine models, is known to induce an increase in the number of c-fos immunoreactive second-order nerve cells projecting to the thalamus. Since the synapses between first- and second-order trigeminal neurons are presumed to be mediated by excitatory amino acids, postsynaptic NMDA receptors should be inhibited by kynurenic acid, an endogenous NMDA receptor antagonist. Kynurenic acid, however, does not cross the blood-brain barrier, and its use as a neuroprotective agent is therefore not feasible. In contrast, kynurenine, from which kynurenic acid is formed on the action of kynurenine aminotransferase, passes the blood-brain barrier without difficulty. After the i.p. injection of kynurenine combined with probenecid it was found that the stimulation-induced increase in the c-fos immunoreactivity of the secondary sensory neurons does not occur.
Knyihár-Csillik
Elizabeth
E
Department of Neurology, University of Szeged, Hungary. knyihar@nepsy.szote.u-szeged.hu
Toldi
József
J
Krisztin-Péva
Beata
B
Chadaide
Zoltán
Z
Németh
Hajnalka
H
Fenyo
Robert
R
Vécsei
László
L
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology / Q000627:therapeutic use; D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004357:Drug Synergism; D004558:Electric Stimulation / Q000009:adverse effects; D007150:Immunohistochemistry; D007737:Kynurenine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D005996:Nitroglycerin / Q000009:adverse effects / Q000037:antagonists & inhibitors; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D011339:Probenecid / Q000494:pharmacology* / Q000627:therapeutic use; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D014665:Vasodilator Agents / Q000009:adverse effects / Q000037:antagonists & inhibitors
D000277:Adjuvants, Pharmaceutic; D000700:Analgesics; D016760:Proto-Oncogene Proteins c-fos; D014665:Vasodilator Agents; D007737:Kynurenine; D005996:Nitroglycerin; D011339:Probenecid