European journal of pain : EJP
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Inflammation of the temporomandibular joint (TMJ) induced by rheumatoid arthritis (RA) have resulted in persistent pain and caused distress to many patients. Considering that not all patients respond to traditional drugs therapy to RA and it has demonstrated that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) into TMJ has a potential peripheral antinociceptive effect, the aim of this study was to evaluate the peripheral effect of 15d-PGJ2 in RA-induced TMJ inflammatory hypernociception. ⋯ In the present study, we demonstrated that 15d-PGJ2 was able to reduce the RA-induced TMJ inflammatory hypernociception by an indirect mechanism. This antinociceptive effect is in part due to decrease of TNF-α, IL-1β and KC levels and PKA/PKCε expression in the TMJ.
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Pain associated with musculoskeletal disorders can be difficult to control and the incorporation of new approaches for its treatment is an interesting challenge. Activation of cannabinoid (CB) receptors decreases nociceptive transmission in acute, inflammatory and neuropathic pain states; however, although the use of cannabis derivatives has been recently accepted as a useful alternative for the treatment of spasticity and pain in patients with multiple sclerosis, the effects of CB receptor agonists in muscular pain have hardly been studied. ⋯ Our results provide evidence that both, CB 1 and CB 2 receptors can contribute to muscular antinociception and, interestingly, suggest that the local administration of CB agonists could be a new and useful pharmacological strategy in the treatment of muscular pain, avoiding adverse effects induced by systemic administration.
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Gamma-aminobutyric acid (GABA) and glutamate (GLU) are involved in nociceptive signals processing in the trigeminal system. In this study, we investigated the influence of excitatory transmission on GABA release in nerve terminals isolated from the rat trigeminal caudal nucleus (TCN). ⋯ These findings indicate that pre-synaptic KA receptors facilitating GABA release from TCN nerve terminals mainly express GLUK2/GLUK3 subunits, supporting the notion that different types of KA receptors are involved in the various stages of pain transmission.
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Randomized Controlled Trial
Effects of dexmedetomidine on conditioned pain modulation in humans.
Systemic administration of dexmedetomidine (DEX; selective α(2) -adrenoceptor agonist) is found to inhibit diffuse noxious inhibitory control in rats, now referred to as conditioned pain modulation (CPM) in humans. The present study was designed to investigate the effect of intravenous administration of DEX on CPM in humans. ⋯ The present study shows that systemic administration of an α(2) -adrenoceptor agonist (DEX), less than the clinical dose, inhibited CPM in humans. These results may provide some mechanistic insight into why many chronic pain patients show impaired CPM.