Effect of Probenecid on the Pain-Related Behaviour and Morphological Markers in Orofacial Formalin Test of the Rat

Author(s): Annamaria Fejes-Szabo , Zsuzsanna Bohar , Gabor Nagy-Grocz , Eniko Vamos , Lilla Tar , Borbala Podor , Janos Tajti , Jozsef Toldi , Laszlo Vecsei , Árpad Pardutz .

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 14 , Issue 3 , 2015

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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 NAD(P)H: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.

Keywords: Caudal part of spinal trigeminal nucleus, c-Fos, interleukin-1β, NAD(P)H:quinone oxidoreductase 1, neuronal nitric oxide synthase, orofacial formalin test, probenecid.

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Article Details

VOLUME: 14
ISSUE: 3
Year: 2015
Page: [350 - 359]
Pages: 10
DOI: 10.2174/1871527314666150225141229
Price: $58

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