title: Effect of probenecid on the pain-related behaviour and morphological markers in orofacial formalin test of the rat.
abstract: Probenecid has been widely used in the treatment of gout, but evidence suggests that it may also have antinociceptive effects in different inflammatory and pain conditions. We examined the potential modulatory effects of probenecid on behavioural and morphological markers in the orofacial formalin test of the rat. One hour after pre-treatment with vehicle or probenecid (1 mmol/kg body weight) intraperitoneally, 50μl 1.5% formalin solution or physiological saline was injected subcutaneously into the right whisker pad of rats. The rubbing activity directed to the injected whisker pad was then measured for a period of 45 minutes. Four hours after formalin injection, the caudal part of spinal trigeminal nucleus was removed and subjected to c-Fos and neuronal nitric oxide synthase (nNOS) immunohistochemistry and to interleukin-1β and
  quinone oxidoreductase 1 (NQO1) Western blot. There was a significant decrease in formalin-induced biphasic behavioural response and c-Fos and nNOS immunoreactivity in the rats that were pre-treated with probenecid. However there were no alterations in expression of interleukin-1β or NQO1 after formalin administration. Our results suggest that probenecid has an anti-nociceptive effect in the trigeminal inflammatory pain model. This effect may be through influencing the release of prostaglandin E2 or desensitizing the transient receptor potential channel subtype A member 1 or the transient receptor potential channel subtype V member 2 or the effect may be through modulating kynurenic acid levels in the central nervous system. Thus, probenecid might be a potential candidate for the treatment of trigeminal activation related pain conditions.
authors.forename: Annamária
authors.initials: A
authors.lastname: Fejes-Szabó
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Bohár
authors.forename: Gábor
authors.initials: G
authors.lastname: Nagy-Grócz
authors.forename: Enikő
authors.initials: E
authors.lastname: Vámos
authors.forename: Lilla
authors.initials: L
authors.lastname: Tar
authors.forename: Borbála
authors.initials: B
authors.lastname: Pődör
authors.forename: János
authors.initials: J
authors.lastname: Tajti
authors.forename: József
authors.initials: J
authors.lastname: Toldi
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Gyorgyi Clinical Centre, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary. vecsei.laszlo@med.u-szeged.hu.
authors.forename: Árpád
authors.initials: Á
authors.lastname: Párdutz
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005157:Facial Pain / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005557:Formaldehyde; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009043:Motor Activity; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010147:Pain Measurement; D011339:Probenecid / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014738:Vibrissae
chemical_list: D000700:Analgesics; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D016760:Proto-Oncogene Proteins c-fos; D005557:Formaldehyde; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D011339:Probenecid