Dental Pulp Autotransplantation: A New Modality of Endodontic Regenerative Therapy-Follow-Up of 3 Clinical Cases.

The aim of this study was to develop a novel method of endodontic therapy, which we refer to as dental pulp autotransplantation. Three patients (2 males and 1 female) were selected for endodontic treatment of a uniradicular premolar and extraction of a third molar (without odontosection). Electric assessment of pulp vitality and computed tomographic imaging were undertaken followed by endodontic access and instrumentation using triantibiotic solution for irrigation in the host tooth. A few minutes before the transplant procedure, the third molar was extracted, the tooth was sectioned with a diamond blade in a low-speed handpiece, and the pulp was carefully removed. After premolar instrumentation, the harvested and preserved pulp tissue was reinserted into the root canal followed by direct pulp capping performed using Biodentine (Septodont, Saint-Maur-des-Fossés, France), a liner of resin-modified glass ionomer cement and composite resin restoration. The teeth were followed up for at least 12 months after the procedures and were analyzed using computed tomographic imaging, electric pulp vitality testing, and Doppler ultrasound examination. At the 3- and 6-month follow-ups, positive pulp vitality and regression of periapical lesions were verified. After 9-12 months, all teeth were revascularized as determined by Doppler imaging, and the tooth vitality was reestablished with no signs of endodontic/periodontal radiolucency or complications. Within the limitations of the study, considering that it was a case series with only 3 patients, we described a highly innovative procedure of pulp autotransplantation, which appears to be feasible, highlighting the potential for clinical application of pulp regeneration using this new modality of endodontic therapy.

Milk Kefir therapy reduces inflammation and alveolar bone loss on periodontitis in rats.

Periodontitis is a chronic inflammatory disease that affects the tooth-supporting tissues. This study evaluated the anti-inflammatory and antiresorptive effects of milk kefir (MK) on periodontitis in rats. Micro-Raman spectroscopy was performed on MK at different fermentation times to verify the presence of Lactobacillus kefiri. From these results, Wistar rats were divided into the following groups: C (Control); EP (experimental periodontitis); K1 (animals that received MK with one day of fermentation); K1+EP; K4 (animals without EP using MK with four days of fermentation) and K4+EP. MK was administered 28 days before EP induction and during the disease development period (11 days). On day 28, in the EP groups, periodontitis was induced. The animals were euthanized on day 39. The hemimaxillae were removed and the following parameters were evaluated: micro-Raman analysis of the presence of inflammation; histomorphometric analysis to quantify alveolar bone loss and immunohistochemistry for IL-6, TNF-α, IL-Iß and IL-10 in the periodontal ligament. Micro-Raman analysis showed that four days fermentation MK has a higher intensity spectrum of L. kefiri. Furthermore, the administration of this probiotic reduced the intensity of the inflammation spectrum when compared to one day fermentation MK. It was observed that the animals from the K4+EP group showed significant reduction of alveolar bone loss, as well as a lower IL-6, TNF-α and IL-Iß immunoexpression and a higher IL-10 immunoexpression, when compared to EP groups. We conclude that MK has anti-inflammatory and antiresorptive effects on periodontitis in rats and that these effects are fermentation time dependent.

Sulfated polysaccharide from the green marine algae Caulerpa racemosa reduces experimental pain in the rat temporomandibular joint.

Temporomandibular disorder is a clinical painful condition in the temporomandibular joint (TMJ) region. The purified sulfated polysaccharide from the green marine algae Caulerpa racemosa (Cr) has provided anti-inflammatory and antinociceptive activity. This study evaluated these effects on a TMJ hypernociception model. Wistar rats (180 - 250 g) were pre-treated (i.v.) with Cr at 0.01, 0.1, or 1 mg/kg or vehicle 30 min before formalin (1.5%/50 µL, i.art.), capsaicin (1.5%/20 µL, i.art.), or serotonin (225 µg/50 µL, i.art.) in the TMJ, and nociceptive behaviors were measured for 45 or 30 min upon inflammatory stimuli. Inflammatory parameters vascular permeability assay, TNF-α, and IL-1ß by ELISA, protein expression of adhesion molecules ICAM-1 and CD55 by Western blot were assessed. The involvement of heme oxygenase-1 (HO-1) and nitric oxide (NO) pathways were assessed by pharmacological inhibition. Cr (1 mg/kg) reduced nociceptive behavior, plasmatic extravasation, TNF-α, and IL-1ß levels, as well as ICAM-1 and CD55 expression in periarticular tissues. Cr antinociceptive effect was not prevented by aminoguanidine, but ZnPP-IX did reduce its antinociceptive effect. Therefore, Cr antinociceptive and anti-inflammatory effects in this experimental model of hypernociception depended on the HO-1 pathway integrity, as well as reducing peripheral inflammatory events, e.g., TNF-α and IL-1ß cytokines levels, ICAM-1 and CD55 expression.

A lectin fraction from green seaweed Caulerpa cupressoides inhibits inflammatory nociception in the temporomandibular joint of rats dependent from peripheral mechanisms.

Temporomandibular disorders are the second most common cause of orofacial pain mediated by inflammatory compounds, which in many cases leads to chronic orofacial pain. This study assessed the antinociceptive and anti-inflammatory effects of a lectin from the green seaweed Caulerpa cupressoides (CcL) on hypernociception inflammatory in TMJ of rats and investigated the involvement of different mechanisms. Rats received i.v. CcL 30 min prior to injection of flogistic agentes or 0.9% saline into the left TMJ. Pretreatment with CcL (0. 1; 1 or 10 mg/kg) promoted a reduction (p < 0.05) of inflammatory hypernociception induced by 1.5% Formalin along with inhibition of inflammatory plasma extravasation, cytokines levels, ciclooxigenase-2, and intercellular adhesion molecule (ICAM-1). CcL was able to inhibit the nociceptive response induced by 1.5% Capsaicin, suggesting that CcL has an antinociceptive effect, acting directly on the primary nociceptive neurons. CcL also inhibited the nociceptive response induced by Carrageenan (100 µg/TMJ) or Serotonin (5-HT) (225 µg/TMJ). In conclusion, the results demonstrate that administration of CcL has a potential antinociceptive and anti-inflammatory effect, with a mechanism that is partially dependent on TNF-α, IL-1ß, COX-2 and ICAM-1 inhibition and independently from the cannabinoide and opioid system and NO/cGMP/PKG/K+ATP channel pathway.

The efficacy of a lectin from Abelmoschus Esculentus depends on central opioid receptor activation to reduce temporomandibular joint hypernociception in rats.

Abelmoschus esculentus is largely cultivated in Northeastern Brazil for medicinal purposes, e.g. inflammatory conditions. This study aimed to evaluate the efficacy of Abelmoschus esculentus lectin (AEL) in reducing formalin-induced temporomandibular joint inflammatory hypernociception in rats. The behavioral experiments were performed in male Wistar rats (180-240 g). Rats were pre-treated (i.v.) with AEL (0.001, 0.01 or 0.1 mg/kg) 30 min before formalin injection (i.art.). To analyze the possible effect of opioid pathways on AEL efficacy, animals were pre-treated with naloxone or CTOP (µ opioid receptor antagonist), naltrindole (δ opioid receptor antagonist) or nor-binaltorphimine (κ opioid receptor antagonist) (i.t.) 15 min before AEL administration followed by intra-TMJ injection of 1.5% formalin. Animals were monitored for a 45-min observation period. TMJ tissue, trigeminal ganglion, and subnucleus caudalis were collected for TNF-α dosage (ELISA). In addition, the vascular permeability was evaluated by Evans Blue extravasation. AEL significantly reduced formalin-induced TMJ inflammatory hypernociception and decreased Evans blue extravasation. It decreased TNF-α levels in the TMJ tissue, trigeminal ganglion, and subnucleus caudalis. AEL antinociceptive effects were not observed in the presence of naltrindole or nor-binaltorphimine, suggesting that AEL efficacy depends on TNF-α inhibition and the activation of δ and κ opioid receptors. AEL has provided prominent analgesic and anti-inflammatory effects in this pre-clinical model of TMJ, supporting its possible use as a pharmacological tool for the management of painful conditions.

Mechanisms involved in antinociception induced by a polysulfated fraction from seaweed Gracilaria cornea in the temporomandibular joint of rats.

Temporomandibular disorder is a common clinical condition involving pain in the temporomandibular joint (TMJ) region. This study assessed the antinociceptive effects of a polysulfated fraction from the red seaweed Gracilaria cornea (Gc-FI) on the formalin-induced TMJ hypernociception in rats and investigated the involvement of different mechanisms. Male Wistar rats were pretreated with injection (sc) of saline or Gc-FI 1h before intra- TMJ injection of formalin to evaluate the nociception. The results showed that pretreatment with Gc-FI significantly reduced formalin-induced nociceptive behavior. Moreover, the antinociceptive effect of the Gc-FI was blocked by naloxone (a non-selective opioid antagonist), suggesting the involvement of opioids selective receptors. Thus, the pretreatment with selective opioids receptors antagonists, reversed the antinociceptive effect of the Gc-FI in the TMJ. The Gc-FI antinociceptive effect depends on the nitric oxide/cyclic GMP/protein kinase G/ATP-sensitive potassium channel (NO/cGMP/PKG/K+ATP) pathway because it was prevented by pretreatment with inhibitors of nitric oxide synthase, guanylate cyclase enzyme, PKG and a K+ATP blocker. In addition, after inhibition with a specific heme oxygenase-1 (HO-1) inhibitor, the antinociceptive effect of the Gc-FI was not observed. Collectively, these data suggest that the antinociceptive effect induced by Gc-FI is mediated by µ/δ/κ-opioid receptors and by activation NO/cGMP/PKG/K+ATP channel pathway, besides of HO-1.

Role of central opioid on the antinociceptive effect of sulfated polysaccharide from the red seaweed Solieria filiformis in induced temporomandibular joint pain.

This study aimed to investigate the effect of sulfated polysaccharide from red seaweed Solieria filiformis (Fraction F II) in the inflammatory hypernociception in the temporomandibular joint (TMJ) of rats. Male Wistar rats were pretreated (30min) with a subcutaneous injection (s.c.) of vehicle or FII (0.03, 0.3 or 3.0mg/kg) followed by intra-TMJ injection of 1.5% Formalin or 5-hydroxytryptamine (5-HT, 225µg/TMJ). In other set of experiments rats were pretreated (15min) with an intrathecal injection of the non-selective opioid receptors Naloxone, or µ-opioid receptor antagonist CTOP, or δ-opioid receptor Naltridole hydrochloride, or κ-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI) followed by injection of FII (s.c.). After 30min, the animals were treated with an intra-TMJ injection of 1.5% formalin. After TMJ treatment, behavioral nociception response was evaluated for a 45-min observation period, animals were terminally anesthetized and periarticular tissue, trigeminal ganglion and subnucleus caudalis (SC) were collected plasma extravasation and ELISA analysis. Pretreatment with F II significantly reduced formalin- and serotonin-induced TMJ nociception, inhibit the plasma extravasation and inflammatory cytokines release induced by 1.5% formalin in the TMJ. Pretreatment with intrathecal injection of Naloxone, CTOP, Naltridole or Nor-BNI blocked the antinociceptive effect of F II in the 1.5% formalin-induced TMJ nociception. In addition, F II was able to significantly increase the ß-endorphin release in the subnucleus caudalis. The results suggest that F II has a potential antinociceptive and anti-inflammatory effect in the TMJ mediated by activation of opioid receptors in the subnucleus caudalis and inhibition of the release of inflammatory mediators in the periarticular tissue.