TY - JOUR
T1 - Peripheral involvement of the nitric oxide-cGMP pathway in the indomethacin-induced antinociception in rat
AU - Ventura-Martínez, Rosa
AU - Déciga-Campos, Myrna
AU - Díaz-Reval, Ma Irene
AU - González-Trujano, Ma Eva
AU - López-Muñoz, Francisco J.
PY - 2004/10/25
Y1 - 2004/10/25
N2 - The role of nitric oxide (NO) in the antinociceptive effect of indomethacin was assessed in the pain-induced functional impairment model in the rat (PIFIR model), a model of inflammatory and chronic pain similar to that observed in clinical gout. Oral administration of indomethacin (5.6 mg/kg), a nonselective cyclooxygenase inhibitor, significantly decreased the nociceptive response elicited by uric acid injected into the knee joint of the right hind limb (2.0±3.0 and 149.7±18.0 area units [au], in the absence and the presence of indomethacin, respectively). This effect of indomethacin was reduced in nearly 50% by local pretreatment with the nonselective inhibitor of NO synthase, N G-l-nitro-arginine methyl ester (l-NAME) (72.9±10.7 vs. 149.7±18.0 au, P<0.05). On the other hand, local administration of l-arginine (a NO synthase substrate) or sodium nitroprusside (a non-enzymatic NO donor) each increased in almost 40% the antinociceptive effect of indomethacin (230.9±12.6 and 226.6±9.7 vs. 149.7±18.0 au, P<0.05), whereas d-arginine (the inactive isomer of arginine) had no effect on the indomethacin antinociceptive response (208.0±34.9 vs. 149.7±18.0 au). These results suggest that, the antinociceptive effect of indomethacin involves, at least in part, the NO-cyclic GMP pathway at peripheral level.
AB - The role of nitric oxide (NO) in the antinociceptive effect of indomethacin was assessed in the pain-induced functional impairment model in the rat (PIFIR model), a model of inflammatory and chronic pain similar to that observed in clinical gout. Oral administration of indomethacin (5.6 mg/kg), a nonselective cyclooxygenase inhibitor, significantly decreased the nociceptive response elicited by uric acid injected into the knee joint of the right hind limb (2.0±3.0 and 149.7±18.0 area units [au], in the absence and the presence of indomethacin, respectively). This effect of indomethacin was reduced in nearly 50% by local pretreatment with the nonselective inhibitor of NO synthase, N G-l-nitro-arginine methyl ester (l-NAME) (72.9±10.7 vs. 149.7±18.0 au, P<0.05). On the other hand, local administration of l-arginine (a NO synthase substrate) or sodium nitroprusside (a non-enzymatic NO donor) each increased in almost 40% the antinociceptive effect of indomethacin (230.9±12.6 and 226.6±9.7 vs. 149.7±18.0 au, P<0.05), whereas d-arginine (the inactive isomer of arginine) had no effect on the indomethacin antinociceptive response (208.0±34.9 vs. 149.7±18.0 au). These results suggest that, the antinociceptive effect of indomethacin involves, at least in part, the NO-cyclic GMP pathway at peripheral level.
KW - (Rat)
KW - Antinociception
KW - Indomethacin
KW - Nitric oxide
KW - PIFIR model
UR - http://www.scopus.com/inward/record.url?scp=7444272524&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2004.09.018
DO - 10.1016/j.ejphar.2004.09.018
M3 - Artículo
SN - 0014-2999
VL - 503
SP - 43
EP - 48
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -