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REDOX MODULATION AT THE PERIPHERAL SITE ALTERS NOCICEPTIVE TRANSMISSION IN VIVO
Author(s) -
Meotti Flavia C,
Coelho Igor S,
Franco Jeferson L,
Dafre Alcir L,
Rocha João BT,
Santos Adair RS
Publication year - 2009
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.05056.x
Subject(s) - ebselen , dithiothreitol , chemistry , pharmacology , glutathione , glutamate receptor , nociception , nmda receptor , nitric oxide , thiol , in vivo , buthionine sulfoximine , biochemistry , receptor , glutathione peroxidase , medicine , biology , enzyme , microbiology and biotechnology , organic chemistry
SUMMARY1 The aim of the present study was to investigate the role of redox modulation during the peripheral nociceptive transmission in vivo . The nociceptive response was evaluated by the amount of time that mice spent licking the footpad injected with glutamate (20 µmol/paw). Thiol groups in footpad tissue were quantified using a colourimetric reaction with 5,5′‐dithio‐bis‐2‐nitrobenzoic acid (DTNB). 2 When coadministered with glutamate, the thiol alkylating agent iodoacetate (200 nmol/paw) caused significant antinociception in footpad tissue, in parallel with a decrease in free thiol groups. Treatment with the reducing agent dithiothreitol (200 nmol/paw) 5 min before glutamate and iodoacetate prevented the antinociception and thiol loss caused by iodoacetate. Injection of 100 nmol/paw ebselen (2‐phenyl‐1,2‐benzisoselenazol‐3[2H]‐one), an in vitro redox modulator of the N ‐methyl‐ d ‐aspartate (NMDA) receptor, also prevented iodoacetate‐induced antinociception. However, ebselen did not prevent thiol loss in the footpad. Dithiothreitol and ebselen had a synergic nociceptive effect with glutamate. 3 Alone, ebselen (100 nmol/paw) exhibited a pronociceptive effect. The nociception induced by ebselen was blocked by glutathione depletion induced by buthionine‐sulphoximine (BSO; 2.5 µmol/paw). In addition, ebselen‐induced nociception was prevented by 75 ± 2% following injection of 5 nmol/paw MK‐801 (an NMDA receptor antagonist). The nitric oxide synthase inhibitor N G ‐nitro‐ l ‐arginine (250 nmol/paw) had no effect on the nociception produced by ebselen. 4 In conclusion, the present paper reports on the effect of redox modulation on the glutamatergic system during peripheral nociceptive transmission in vivo . Antinociception was directly correlated with the availability of thiol groups, whereas the pronociceptive response of the reducing agents likely occurs via positive modulation of the NMDA receptor.