Is the injection of tramadol effective at control of pain after impacted mandibular third molar extractions? A systematic review and meta-analysis.

BACKGROUND: Third molar extraction is among the most common surgical procedures performed by oral-maxillofacial surgeons. Postoperative pain, swelling and trismus are common, especially in wisdom teeth, due to trauma to local tissues and the duration of the surgical procedure, among other factors. MATERIAL AND METHODS: This systematic review was conducted in accordance with the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' in order to answer the focused question: 'Is the local submucosal injection of tramadol effective at the control of postoperative pain in patients submitted to impacted mandibular third molar extractions?'. We analyzed papers published until March 30, 2021 in the MEDLINE|PubMed, Web of Science and Cochrane Library databases. Gray literature was also consulted. Standard pairwise meta-analyses of direct comparisons were performed using a fixed-effect model; I2 ≥ 50 % or ≥ 75 % indicated moderate or high heterogeneity, respectively. Risk of bias was assessed by Cochrane Collaboration's tool. RESULTS: In total, 172 participants (98 males and 74 females, aged 18 or over) from three randomized placebo-controlled trials were considered for analysis. The submucosal injection of 2 ml of tramadol adjacent to the impacted mandibular third molar was effective in controlling pain up to 6-hours after surgery, in increasing the onset of consumption of rescue analgesic and in reducing the total number of rescue analgesics used. CONCLUSIONS: The submucosal injection of tramadol can be considered a safe and effective procedure for pain control after impacted mandibular third molar extractions.

Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways.

Neurotrophins protect neurons against glutamate excitotoxicity, but the signaling mechanisms have not been fully elucidated. We studied the role of the phosphatidylinositol 3-kinase (PI3-K) and Ras/mitogen-activated protein kinase (MAPK) pathways in the protection of cultured hippocampal neurons from glutamate induced apoptotic cell death, characterized by nuclear condensation and activation of caspase-3-like enzymes. Pre-incubation with the neurotrophin brain-derived neurotrophic factor (BDNF), for 24 h, reduced glutamate-evoked apoptotic morphology and caspase-3-like activity, and transiently increased the activity of the PI3-K and of the Ras/MAPK pathways. Inhibition of the PI3-K and of the Ras/MAPK signaling pathways abrogated the protective effect of BDNF against glutamate-induced neuronal death and similar effects were observed upon inhibition of protein synthesis. Moreover, incubation of hippocampal neurons with BDNF, for 24 h, increased Bcl-2 protein levels. The results indicate that the protective effect of BDNF in hippocampal neurons against glutamate toxicity is mediated by the PI3-K and the Ras/MAPK signaling pathways, and involves a long-term change in protein synthesis.