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Peripheral antinociceptive effect of pertussis toxin: activation of the arginine/NO/cGMP/PKG/ ATP‐sensitive K + channel pathway
Author(s) -
Brito Gerly A. C.,
Sachs Daniela,
Cunha Fernando Q.,
Vale Mariana L.,
Lotufo Celina M. C.,
Ferreira Sérgio H.,
Ribeiro Ronaldo. A.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.04991.x
Subject(s) - pertussis toxin , nitric oxide , chemistry , pharmacology , soluble guanylyl cyclase , channel blocker , nociception , nitric oxide synthase , prostaglandin e , protein kinase a , prostaglandin , receptor , g protein , medicine , kinase , biochemistry , guanylate cyclase , calcium , organic chemistry
The aim of the present study was to determine the effect of pertussis toxin (PTX) on inflammatory hypernociception measured by the rat paw pressure test and to elucidate the mechanism involved in this effect. In this test, prostaglandin E 2 (PGE 2 ) administered subcutaneously induces hypernociception via a mechanism associated with neuronal cAMP increase. Local intraplantar pre‐treatment (30 min before), and post‐treatment (5 min after) with PTX (600 ng/paw1, in 100 µL) reduced hypernociception induced by prostaglandin E 2 (100 ng/paw, in 100 µL, intraplantar). Furthermore, local intraplantar pre‐treatment (30 min before) with PTX (600 ng/paw, in 100 µL) reduced hypernociception induced by DbcAMP, a stable analogue of cAMP (100 µg/paw, in 100 µL, intraplantar), which indicates that PTX may have an effect other than just G i /G 0 inhibition. PTX‐induced analgesia was blocked by selective inhibitors of nitric oxide synthase (L‐NMMA), guanylyl cyclase (ODQ), protein kinase G (KT5823) and ATP‐sensitive K + channel (Kir6) blockers (glybenclamide and tolbutamide). In addition, PTX was shown to induce nitric oxide (NO) production in cultured neurons of the dorsal root ganglia. In conclusion, this study shows a peripheral antinociceptive effect of pertussis toxin, resulting from the activation of the arginine/NO/cGMP/PKG/ATP‐sensitive K + channel pathway.