Early Phase of Type 1 Diabetes Decreases the Responsiveness of C-Fiber Nociceptors in the Temporomandibular Joint of Rats.

Diabetes is a chronic degenerative disease that represent a major threat to public health worldwide. Once the disease is established, one of the major concerns about the diabetes complications is the development of neuropathy. This study established an experimental model that evaluates the effect of type 1 diabetes on nociceptive challenges in the temporomandibular joint (TMJ). Streptozotocin-induced type 1 (STZ 75 mg/Kg) diabetes inhibited the responsiveness of C-fibers nociceptors located in the TMJ of Wistar rats since seventh day after the disease induction. Diabetes-induced hyporesponsiveness of C-fibers nociceptors was associated with significantly reduction of protein level of neuropeptides Substance P and Calcitonin Gene Related Peptide. Diabetic animals pre-treated with Protein Kinase C (PKC)-α and -ß inhibitor (GO6976) or PKC-ß inhibitor (LY333531) significantly increased capsaicin-induced nociception in the TMJ higher protein levels of Na+/K+-ATPase pump in the trigeminal ganglia. On the other hand, although diabetes inhibits formalin-induced nociception higher protein levels of pro-inflammatory cytokine IL1-ß and chemokine CINC-1/CXCL-1 were observed. Overall, the results of the present work suggest that diabetes causes a hyporesponsiveness of C-fiber and a potentialization of the inflammatory response which may result in the degenerative process of periarticular tissues without pain perception.

The anti-inflammatory effect of tramadol in the temporomandibular joint of rats.

Tramadol is a centrally acting analgesic drug able to prevent nociceptor sensitization when administered into the temporomandibular joint (TMJ) of rats. The mechanism underlying the peripheral anti-inflammatory effect of tramadol remains unknown. This study demonstrated that intra-TMJ injection of tramadol (500µg/TMJ) was able to inhibit the nociceptive response induced by 1.5% formalin or 1.5% capsaicin, suggesting that tramadol has an antinociceptive effect, acting directly on the primary nociceptive neurons activating the nitric oxide/cyclic guanosine monophosphate signaling pathway. Tramadol also inhibited the nociceptive response induced by carrageenan (100µg/TMJ) or 5-hydroxytryptamine (225µg/TMJ) along with inhibition of inflammatory cytokines levels, leukocytes migration and plasma extravasation. In conclusion, the results demonstrate that peripheral administration of tramadol has a potential antinociceptive and anti-inflammatory effect. The antinociceptive effect is mediated by activation of the intracellular nitric oxide/cyclic guanosine monophosphate pathway, at least in part, independently from the opioid system.

Quercetin inhibits inflammatory bone resorption in a mouse periodontitis model.

Periodontitis is a disease that leads to bone destruction and represents the main cause of tooth loss in adults. The development of aggressive periodontitis has been associated with increased inflammatory response that is induced by the presence of a subgingival biofilm containing Aggregatibacter actinomycetemcomitans. The flavonoid quercetin (1) is widespread in vegetables and fruits and exhibits many biological properties for possible medical and clinical applications such as its anti-inflamatory and antioxidant effects. Thus, in the present study, the properties of 1 have been evaluated in bone loss and inflammation using a mouse periodontitis model induced by A. actinomycetemcomitans infection. Subcutaneous treatment with 1 reduced A. actinomycetemcomitans-induced bone loss and IL-1ß, TNF-α, IL-17, RANKL, and ICAM-1 production in the gingival tissue without affecting bacterial counts. These results demonstrated that quercetin exhibits protective effects in A. actinomycetemcomitans-induced periodontitis in mice by modulating cytokine and ICAM-1 production.