The role of endogenous opioid peptides in the antinociceptive effect of 15-deoxyΔ12,14-prostaglandin J2 in the temporomandibular joint

• The peripheral antinociceptive effect of 15d-PGJ2 is mediated by PPAR-gamma.
• PPAR-gamma are expressed in the inflammatory cells cells of TMJ tissues.
• Activated by 15d-PGJ2, PPAR-gamma induces the release of endogenous opioids.
• The endogenous opioids induce the activation of their receptors in primary sensory neurons.
• Opioid receptors induce the activation of antinociceptive NO/cGMP/K+ATP channel.

We have previously demonstrated that peripheral administration of 15d-PGJ2 in the Temporomandibular joint (TMJ) of rats can prevent nociceptor sensitization, mediated by peroxisome proliferator activated receptor-γ (PPAR-γ), and κ- and δ- opioid receptors. However, the mechanism that underlies the signaling of PPAR-γ (upon activation by 15d-PGJ2) to induce antinociception, and how the opioid receptors are activated via 15d-PGJ2 are not fully understood. This study demonstrates that peripheral antinociceptive effect of 15d-PGJ2 is mediated by PPAR-γ expressed in the inflammatory cells of TMJ tissues. Once activated by 15d-PGJ2, PPAR-γ induces the release of β-endorphin and dynorphin, which activates κ- and δ-opioid receptors in primary sensory neurons to induce the antinociceptive effect.