TY - JOUR
T1 - Analysis of the mechanisms underlying the antinociceptive effect of epicatechin in diabetic rats
AU - Quiñonez-Bastidas, Geovanna Nallely
AU - Cervantes-Durán, Claudia
AU - Rocha-González, Héctor Isaac
AU - Murbartián, Janet
AU - Granados-Soto, Vinicio
N1 - Funding Information:
The authors greatly appreciate the bibliographic and technical assistance of Héctor Vázquez and Guadalupe C. Vidal-Cantú, respectively. This work is part of the Ph.D. dissertation of Geovanna N. Quiñonez-Bastidas. Geovanna N. Quiñonez-Bastidas and Claudia Cervantes-Durán are Conacyt fellows. This work was partially supported by Conacyt 179294 (VG-S), 154880 (HIR-G) and ICyTDF 332-2011 (JM) grants. Support by CNPq (400186/2011-0) is kindly acknowledged. Vinicio Granados-Soto is a visiting professor at the Department of Pharmacology, School of Medicine of Ribeirão Preto, University of Sao Paulo, Brazil.
PY - 2013/10/17
Y1 - 2013/10/17
N2 - Aims The purpose of this study was to investigate the antinociceptive effect of epicatechin as well as the possible mechanisms of action in diabetic rats. Main methods Rats were injected with streptozotocin to produce hyperglycemia. The formalin test was used to assess the nociceptive activity. Key findings Acute pre-treatment with epicatechin (0.03-30 mg/kg, i.p.) prevented formalin-induced nociception in diabetic rats. Furthermore, daily or every other day treatment for 2 weeks with epicatechin (0.03-30 mg/kg, i.p.) also prevented formalin-induced nociception in diabetic rats. Acute epicatechin-induced antinociception was prevented by l-NAME (N ω-nitro-l-arginine methyl ester hydrochloride, 1-10 mg/kg, non-selective nitric oxide synthesis inhibitor), 7-nitroindazole (0.1-1 mg/kg, selective neuronal nitric oxide synthesis inhibitor), ODQ (1H-(1,2,4)- oxadiazolo(4,2-a)quinoxalin-1-one, 0.2-2 mg/kg, guanylyl cyclase inhibitor) or glibenclamide (1-10 mg/kg, ATP-sensitive K+ channel blocker). Moreover, epicatechin (3 mg/kg)-induced antinociception was fully prevented by methiothepin (0.1-1 mg/kg, serotonergic receptor antagonist), WAY-100635 (0.03-0.3 mg/kg, selective 5-HT1A receptor antagonist) or SB-224289 (0.03-0.3 mg/kg, selective 5-HT1B receptor antagonist). In contrast, BRL-15572 (0.03-0.3 mg/kg, selective 5-HT1D receptor antagonist) only slightly prevented the antinociceptive effect of epicatechin. Naloxone (0.1-1 mg/kg, opioid antagonist) did not modify epicatechin's effect. Significance Data suggest the involvement of the nitric oxide-cyclic GMP-K+ channel pathway as well as activation of 5-HT1A and 5HT1B, and at a lesser extent, 5-HT1D, but not opioid, receptors in the antinociceptive effect of epicatechin in diabetic rats. Our data suggest that acute or chronic treatment with epicatechin may prove to be effective to treat nociceptive hypersensitivity in diabetic patients.
AB - Aims The purpose of this study was to investigate the antinociceptive effect of epicatechin as well as the possible mechanisms of action in diabetic rats. Main methods Rats were injected with streptozotocin to produce hyperglycemia. The formalin test was used to assess the nociceptive activity. Key findings Acute pre-treatment with epicatechin (0.03-30 mg/kg, i.p.) prevented formalin-induced nociception in diabetic rats. Furthermore, daily or every other day treatment for 2 weeks with epicatechin (0.03-30 mg/kg, i.p.) also prevented formalin-induced nociception in diabetic rats. Acute epicatechin-induced antinociception was prevented by l-NAME (N ω-nitro-l-arginine methyl ester hydrochloride, 1-10 mg/kg, non-selective nitric oxide synthesis inhibitor), 7-nitroindazole (0.1-1 mg/kg, selective neuronal nitric oxide synthesis inhibitor), ODQ (1H-(1,2,4)- oxadiazolo(4,2-a)quinoxalin-1-one, 0.2-2 mg/kg, guanylyl cyclase inhibitor) or glibenclamide (1-10 mg/kg, ATP-sensitive K+ channel blocker). Moreover, epicatechin (3 mg/kg)-induced antinociception was fully prevented by methiothepin (0.1-1 mg/kg, serotonergic receptor antagonist), WAY-100635 (0.03-0.3 mg/kg, selective 5-HT1A receptor antagonist) or SB-224289 (0.03-0.3 mg/kg, selective 5-HT1B receptor antagonist). In contrast, BRL-15572 (0.03-0.3 mg/kg, selective 5-HT1D receptor antagonist) only slightly prevented the antinociceptive effect of epicatechin. Naloxone (0.1-1 mg/kg, opioid antagonist) did not modify epicatechin's effect. Significance Data suggest the involvement of the nitric oxide-cyclic GMP-K+ channel pathway as well as activation of 5-HT1A and 5HT1B, and at a lesser extent, 5-HT1D, but not opioid, receptors in the antinociceptive effect of epicatechin in diabetic rats. Our data suggest that acute or chronic treatment with epicatechin may prove to be effective to treat nociceptive hypersensitivity in diabetic patients.
KW - Diabetes
KW - Epicatechin
KW - K channels
KW - Nitric oxide
KW - Nociception
KW - Serotonin receptors
UR - http://www.scopus.com/inward/record.url?scp=84885174559&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2013.08.022
DO - 10.1016/j.lfs.2013.08.022
M3 - Artículo
SN - 0024-3205
VL - 93
SP - 637
EP - 645
JO - Life Sciences
JF - Life Sciences
IS - 17
ER -