Activation of peripheral kappa/delta opioid receptors mediates 15-deoxy-(Delta12,14)-prostaglandin J2 induced-antinociception in rat temporomandibular joint.
This study assessed the effect of the agonist 15d-PGJ(2) administered into the rat temporomandibular joint (TMJ) on nociceptive behavioral and the anti-inflammatory potential of this prostaglandin on TMJ. It was observed that 15-deoxy-(Delta12,14)-prostaglandin J(2) (15d-PGJ(2)) significantly reduced formalin-induced nociceptive behavior in a dose dependent manner, however injection of 15d-PGJ(2) into the contralateral TMJ failed to reduce such effects. This antinociceptive effect is dependent on peroxisome proliferator-activated receptors-gamma (PPAR-gamma) since pre-treatment with GW9662 (PPAR-gamma receptor antagonist) blocked the antinociceptive effect of 15d-PGJ(2) in the TMJ. In addition, the antinociceptive effect of 15d-PGJ(2) was also blocked by naloxone suggesting the involvement of peripheral opioids in the process. Confirming this hypothesis pre-treatment with kappa, delta, but not mu receptor antagonists significantly reduced the antinociceptive effect of 15d-PGJ(2) in the TMJ. Similarly to opioid agonists, the 15d-PGJ(2) antinociceptive action depends on the nitric oxide (NO)/guanilate cyclase (cGMP)/ATP-sensitive potassium channel blocker(K(+)(ATP)) channel pathway since it was prevented by the pre-treatment with the inhibitors of nitric oxide synthase (NOS; aminoguanidine), cGMP (ODQ), or the K(+)(ATP) (glibenclamide). In addition, 15d-PGJ(2) (100 ng/TMJ) inhibits 5-HT-induced TMJ hypernociception. Besides, TMJ treated with 15d-PGJ(2) showed lower vascular permeability, assessed by Evan's Blue extravasation, and also lower neutrophil migration induced by carrageenan administration. Taken together, these results demonstrate that 15d-PGJ(2) has a potential peripheral antinociceptive and anti-inflammatory effect in the TMJ via PPAR-gamma activation. The results also suggest that 15d-PGJ(2) induced-peripheral antinociceptive response in the TMJ is mediated by kappa/delta opioid receptors by the activation of the intracellular l-arginine/NO/cGMP/K(+)(ATP) channel pathway. The pharmacological properties of the peripheral administration of 15d-PGJ(2) highlight the potential use of this PPAR-gamma agonist on TMJ inflammatory pain conditions.
Pena-dos-Santos
D R
DR
Laboratory of Biopathology and Molecular Biology, University of Uberaba, Uberaba, Brazil.
Severino
F P
FP
Pereira
S A L
SA
Rodrigues
D B R
DB
Cunha
F Q
FQ
Vieira
S M
SM
Napimoga
M H
MH
Clemente-Napimoga
J T
JT
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D013704:Temporomandibular Joint / Q000187:drug effects* / Q000378:metabolism
C477819:15-deoxyprostaglandin J2; D000700:Analgesics; D054086:KATP Channels; D047495:PPAR gamma; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D005557:Formaldehyde; D012701:Serotonin; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D015230:Prostaglandin D2