Flupirtine inhibits calcitonin-gene related peptide release from rat brainstem in vitro

Giuseppe Tringali, Maria Cristina Greco, Alessandro Capuano, Giuseppe Guerriero, Diego Currò, Pierluigi Navarra

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We have previously shown that the nonopioid analgesic flupirtine possesses analgesic activity in the orofacial formalin test in vivo in the rat. However, this paradigm does not allow to distinguish between central and peripheral site of action of the drug. In this study we used a recently characterized in vitro model, consisting in acute rat brainstem explants, to investigate whether flupirtine analgesia may be, at least in part, attributed to interference with neurotransmission between the first and the second order neurons of the trigeminal system, occurring within the brainstem. We used acute rat brainstem explants; CGRP released into the incubation medium was taken as a marker of CGRP release from central terminals of trigeminal ganglion afferent neurons within the brainstem. CGRP levels were measured by radioimmunoassay under basal conditions or in the presence of flupirtine, alone or with putative antagonist XE-991. We found that flupirtine inhibits in a concentration-dependent manner both basal and capsaicin-stimulated CGRP release from rat brainstem. This effect is mimicked by the flupirtine analogue retigabine, and is counteracted by the Kv7 blocker XE-991. These findings provide in vitro evidence that the analgesic activity of flupirtine may be related to interference with pain neurotransmission at the brainstem level. Pharmacological data suggests that such effect is related to opening of Kv7 channels on first-order neuronal nerve ending, and the subsequent inhibition of neurotransmitter release, since the effect is mimicked by the Kv7 opener retigabine and is counteracted by the Kv7 blocker XE-991.

Original languageEnglish
Pages (from-to)332-335
Number of pages4
JournalNeuroscience Letters
Volume506
Issue number2
DOIs
Publication statusPublished - Jan 11 2012

Fingerprint

flupirtine
Calcitonin Gene-Related Peptide
Brain Stem
Synaptic Transmission
Analgesics
Non-Narcotic Analgesics
Afferent Neurons
Trigeminal Ganglion
Nerve Endings
Capsaicin
Pain Measurement
Analgesia
Radioimmunoassay
Neurotransmitter Agents
In Vitro Techniques
Pharmacology

Keywords

  • Brainstem
  • Capsaicin
  • CGRP
  • Flupirtine
  • Rat
  • Retigabine
  • XE-991

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Flupirtine inhibits calcitonin-gene related peptide release from rat brainstem in vitro. / Tringali, Giuseppe; Greco, Maria Cristina; Capuano, Alessandro; Guerriero, Giuseppe; Currò, Diego; Navarra, Pierluigi.

In: Neuroscience Letters, Vol. 506, No. 2, 11.01.2012, p. 332-335.

Research output: Contribution to journalArticle

Tringali, Giuseppe ; Greco, Maria Cristina ; Capuano, Alessandro ; Guerriero, Giuseppe ; Currò, Diego ; Navarra, Pierluigi. / Flupirtine inhibits calcitonin-gene related peptide release from rat brainstem in vitro. In: Neuroscience Letters. 2012 ; Vol. 506, No. 2. pp. 332-335.
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