RESUMEN
BACKGROUND: P2X7 receptors are responsible for triggering inflammatory responses contributing to processes of pain in articular tissues. This study aimed to investigate whether the activation of the P2X7 receptor located in the temporomandibular joint (TMJ) tissues induces nociception through an inflammatory mechanisms and/or the activation of C-fibres (small-diameter primary afferents) of rats' TMJ. METHODS: The TMJ hypernociception induced by the activation of P2X7 receptor was assessed by measuring the behavioural nociceptive responses. After behavioural experiments, the animals were terminally anaesthetized and periarticular tissues were removed and homogenate for enzyme-linked immunosorbent assay, leukocyte infiltration and western blotting analysis. RESULTS: The nonselective P2X7 receptor agonist BzATP induced a dose-dependent TMJ nociception, which was blocked by the selective P2X7 receptor antagonist A-438079. The co-administration of the selective ß2-adrenoceptor antagonist (ICI-118,551) and the pre-treatment with cyclooxygenase inhibitor indomethacin or with the nonspecific selectin inhibitor Fucoidan significantly reduced BzATP-induced TMJ nociception. BzATP also induced an increase of pro-inflammatory cytokines TNFα, IL-1ß and CINC-1 levels, as well as leukocyte recruitment in TMJ tissue, effects that were reduced by A-438079. Moreover BzATP-induced TMJ nociception was inhibited in rats neonatal-treated with Capsaicin (depleting C-fibers). Finally, BzATP-induced an increase in TRPV1 expression in TMJ tissue. CONCLUSIONS: These findings suggest that P2X7 receptor activation in TMJ of rats induces nociceptive responses mediated by sympathomimetic amines, prostaglandins, leukocyte migration and increased levels of pro-inflammatory cytokines. Furthermore, the P2X7 receptor activation induces nociceptive responses dependent on the activation of the primary afferent nociceptors of rats' TMJ. SIGNIFICANCE: The activation of P2X7 receptors has an essential role in TMJ nociception and could be an interesting target to control the inflammatory pain in temporomandibular disorders.
Asunto(s)
Nocicepción , Trastornos de la Articulación Temporomandibular , Animales , Dolor , Ratas , Ratas Wistar , Articulación Temporomandibular , Trastornos de la Articulación Temporomandibular/inducido químicamenteRESUMEN
Pharmacological agents directed to either opioid receptors or peroxisome proliferator-activated receptor gamma (PPARγ) at peripheral tissues reduce behavioral signs of persistent pain. Both receptors are expressed in muscle tissue, but the contribution of PPARγ activation to muscle pain and its modulation by opioid receptors remains unknown. To address this question, we first tested whether the endogenous PPARγ ligand 15d-PGJ2 would decrease mechanical hyperalgesia induced by carrageenan administration into the gastrocnemius muscle of rats. Next, we used receptor antagonists to determine whether the antihyperalgesic effect of 15-deoxyΔ-12,14-prostaglandin J2 (15d-PGJ2) was PPARγ- or opioid receptor-dependent. Three hours after carrageenan, muscle hyperalgesia was quantified with the Randall-Selitto test. 15d-PGJ2 prevented carrageenan-induced muscle hyperalgesia in a dose-dependent manner. The antihyperalgesic effect of 15d-PGJ2 was dose-dependently inhibited by either the PPARγ antagonist, 2-chloro-5-nitro-N-phenylbenzamide, or by the opioid receptor antagonist, naloxone. We conclude that 15d-PGJ2 targets PPARγ and opioid receptors to prevent muscle hyperalgesia. We suggest that local PPARγ receptors are important pharmacological targets for inflammatory muscle pain.