Oral Surgery Model Research Articles

A Review of Sedation Agents.

The oral and maxillofacial surgery model of anesthesia delivery is the subject of some controversy. However, a long track record of patient safety provides compelling support for the dual role of the oral and maxillofacial surgeon as proceduralist and anesthetist. Among the elements critical to continued success is a clear understanding of the pharmacology of the agents used to produce sedation and general anesthesia. This review highlights 6 sedation agents used as part of a balanced anesthesia technique in oral and maxillofacial surgery.

Effect of coronavirus disease 2019 outbreak on the specialty of maxillofacial surgery

The outbreak of coronavirus disease 2019 (COVID-19) has specific implications for oral and maxillofacial surgeons due to an accrued risk of exposure to the virus throughout surgical procedures involving the aerodigestive tract. Maxillofacial surgical procedures due to direct contact with oral and nasal mucosa that area unit thought of areas of high risk of infection in virtue of viral charge and great risk of exposure to COVID-19. Maxillofacial surgery represents associate example of a specialty that has had to adapt to the present outbreak, due to the subspecialties of medical specialty and medicine. Considering the numerous sociopolitical things in every country, the oral and maxillofacial surgery model was thought of acceptable to evaluate the safety measures taken by the healthcare establishments.

A Randomized Clinical Trial Comparing 2 Ibuprofen Formulations in Patients with Acute Odontogenic Pain

IntroductionIbuprofen sodium dihydrate, a new formulation of ibuprofen, was introduced with the claim of faster onset of analgesia. Most of the data on this new ibuprofen formulation are drawn from studies using the oral surgery model. Because this model differs significantly from the endodontic pain model, we conducted a study comparing ibuprofen sodium dihydrate with conventional ibuprofen acid in endodontic pain patients. MethodsThis randomized, double-masked study recruited subjects experiencing moderate to severe pain from a tooth diagnosed with symptomatic irreversible pulpitis and symptomatic apical periodontitis (n = 41). Subjects were randomized to receive 400 mg ibuprofen acid (Advil; Pfizer, Madison, NJ) or an equivalent dose of 512 mg ibuprofen sodium dihydrate (Advil Sodium, Pfizer). The outcome measures were time to onset of 50% pain relief recorded using a stopwatch, reduction in spontaneous pain experienced on a 100-mm visual analog scale, and change in mechanical allodynia measured using a bite force transducer. The last 2 measures were obtained before and 60 minutes after administration of the drug. ResultsThe median time to onset of 50% pain relief after administration of ibuprofen sodium dihydrate was significantly faster compared with ibuprofen acid (26.5 vs 44 minutes, P = .08). Ibuprofen sodium dihydrate provided a greater reduction in spontaneous pain (50.8% vs 33.3%, P < .05) and mechanical allodynia (15% vs 9%, P > .05). ConclusionsIn endodontic pain patients, a single dose of ibuprofen sodium dihydrate provides faster onset of pain relief and a greater reduction in spontaneous and evoked pain compared with ibuprofen acid.

Upregulation of IL-6, IL-8 and CCL2 gene expression after acute inflammation: Correlation to clinical pain

Tissue injury initiates a cascade of inflammatory mediators and hyperalgesic substances including prostaglandins, cytokines and chemokines. Using microarray and qRT-PCR gene expression analyses, the present study evaluated changes in gene expression of a cascade of cytokines following acute inflammation and the correlation between the changes in the gene expression level and pain intensity in the oral surgery model of tissue injury and acute pain. Tissue injury resulted in a significant upregulation in the gene expression of interleukin-6 (IL-6; 63.3-fold), IL-8 (8.1-fold), chemokine (C-C motif) ligand 2 (CCL2; 8.9-fold), chemokine (C-X-C motif) ligand 1 (CXCL1; 30.5-fold), chemokine (C-X-C motif) ligand 2 (CXCL2; 26-fold) and annexin A1 (ANXA1; 12-fold). The upregulation of IL-6 gene expression was significantly correlated to the upregulation of IL-8, CCL2, CXCL1 and CXCL2 gene expression. Interestingly, the tissue injury-induced upregulation of IL-6, IL-8 and CCL2 gene expression, was positively correlated to pain intensity at 3 h post-surgery, the onset of acute inflammatory pain. However, ketorolac treatment did not have a significant effect on the gene expression of IL-6, IL-8, CCL2, CXCL2 and ANXA1 at the same time point of acute inflammation. These results demonstrate that the upregulation of IL-6, IL-8 and CCL2 gene expression contributes to the development of acute inflammation and inflammatory pain. The lack of effect of ketorolac on the expression of these gene products may be related to the ceiling analgesic effects of non-steroidal anti-inflammatory drugs.

11th International Dental Congress on Modern Pain Control The Essential Role of Dental Anesthesiology in the 21st Century Safe and Comfortable Dentistry 4th–7th October, 2006

11th International Dental Congress on Modern Pain Control The Essential Role of Dental Anesthesiology in the 21st Century Safe and Comfortable Dentistry 4th–7th October, 2006

COX-2 inhibitors and pain after oral surgery – pertinent papers 2002–2003

Khan AA, Brahim JS, Rowan JS, Dionne RA. In vivo selectivity of a selective cyclooxygenase 2 inhibitor in the oral surgery model. Clin Pharmacol Ther 2002;72:44–9.Prostanoids formed by cyclo-oxygenase inhibitors have an important role in treating pain and inflammation. It is thought that COX-1 is constitutively expressed, whereas COX-2 is induced during inflammation. This study examined the in vivo selectivity of celecoxib, a COX-2 inhibitor, and evaluated whether estimates of selectivity that are based on in vitro and ex vivo analyses are reliable indicators of in vivo selectivity.

Capsaicin as a Preventive Analgesic in the Oral Surgery Model

Capsaicin as a Preventive Analgesic in the Oral Surgery Model

Effects of a dual COX-1/-2 inhibitor and a selective COX-2 inhibitor on pro-inflammatory gene expression in a clinical model of tissue injury

Aims COX-1 expression is significantly decreased and COX-2 expression significantly increased 4 hours after surgery, but both return to pre-surgical levels by 48 hours in acutely inflamed human tissue (Lee et al, Soc. for Neurosci. 2004). This study evaluated the effect of a dual COX-1/-2 inhibitor (ibuprofen) and a selective COX-2 inhibitor (rofecoxib) on expression patterns of pro-inflammatory genes related to prostaglandin (PG) formation in the oral surgery model. Methods Pre- and post-surgical (48 hours) biopsy samples were taken from 64 patients undergoing surgical removal of impacted third molars. For evaluation of transcriptional activity, real-time PCR assays were performed. Results We found little detectable change in COX-1 expression but wide variation in COX-2 expression associated with drug administration: no change in the placebo group but increased COX-2 mRNA from ibuprofen (p rofecoxib > placebo), and 15-PGDH related to PG degradation, was significantly decreased (ibuprofen < rofecoxib < placebo). Conclusions These findings demonstrate that a dual COX-1/-2 inhibitor and a selective COX-2 inhibitor change expression patterns of pro-inflammatory genes following tissue injury that stimulate the arachidonic acid cascade and may attenuate the inhibitory actions of these drugs by increased production of PG. Clinical Pharmacology & Therapeutics (2005) 77, P9–P9; doi: 10.1016/j.clpt.2004.11.035

Analgesic Effect of Sustained‐Release Flurbiprofen Administered at the Site of Tissue Injury in the Oral Surgery Model

Nonsteroidal anti-inflammatory drugs produce their analgesic and adverse effects through interaction with cyclooxygenase in a variety of tissues. The authors evaluated the therapeutic potential of administering a sustained-release formulation of flurbiprofen into a surgical wound following oral surgery to produce analgesia at the site of injury while minimizing exposure to potential targets for toxicity. Subjects (N = 98) received 1 of 8 treatments: flurbiprofen in a microparticle formulation in doses of 3.125 mg, 6.25 mg, 12.5 mg, 25 mg, or 50 mg; PO flurbiprofen 25 mg or 50 mg; or placebo. The flurbiprofen microparticle formulation or matching placebo was placed into the extraction sites at the end of surgery (removal of 2 lower impacted third molars). The sum of the pain visual analog scale over the 6-hour observation period demonstrated significantly less pain (P < .05) for flurbiprofen microparticle in comparison with placebo. Fewer subjects remedicated in the flurbiprofen microparticle drug groups, primarily for the 12.5-mg and higher doses. The incidence of adverse effects and local complications did not differ across groups. These data suggest that direct administration of flurbiprofen in a microparticle formulation at a site of tissue injury delays the onset and lowers the intensity of postoperative pain at lower doses than usually administered orally.

Effect of a selective COX-2 inhibitor in the development of central sensitization in the oral surgery model

Nociceptive input from surgical insult and postoperative inflammation contribute to the development of central sensitization, yet their relative contributions have not been evaluated. COX-1 and -2 catalyze prostaglandin synthesis, with COX-1 being primarily responsible for PGE2 production over the first 1–2 hours with COX-2 regulation at later time points. This study evaluated the effect of COX-2 mediated prostanoid production to nociceptive input contributing to the development of central sensitization in the oral surgery model with either 50 mg rofecoxib or placebo administered preoperatively and lidocaine or long-acting bupivicaine used for local anesthesia. Microdialysis was used to collect submucosal perfusate from the surgical site for four hours postoperatively and pain report recorded concurrently. Both rofecoxib and bupivicaine suppressed pain in the immediate postoperative period independently and additively. PGE2 levels were significantly suppressed by rofecoxib as compared to placebo across the last two hours of the postoperative period (p < 0.05). TXB2 levels did not differ significantly between groups during the postoperative period. The local anesthetic did not have any effect on PGE2 or TXB2 levels. The suppression of PGE2 during the later time points suggests that inhibition of cytokine mediated postoperative inflammation limits the development of sensitization following surgery. Clinical Pharmacology & Therapeutics (2004) 75, P4–P4; doi: 10.1016/j.clpt.2003.11.014

In vivo selectivity of a selective cyclooxygenase 2 inhibitor in the oral surgery model

Prostanoids formed by cyclooxygenase play an important role in pain and the induction of inflammation. It is generally believed that COX-1 is constitutively expressed, whereas COX-2 is primarily inducible during inflammation. This study examined the in vivo selectivity of celecoxib, a COX-2 inhibitor, and evaluated whether estimates of selectivity that are based on in vitro and ex vivo analyses are reliable indicators of in vivo selectivity. Subjects (103 outpatients undergoing surgical removal of two impacted mandibular third molars) received either 200 mg celecoxib, 600 mg ibuprofen, or placebo 8 hours before surgery and a second dose 1 hour before surgery. After surgery, microdialysis probes were placed in the surgical sites for collection of inflammatory transudate. Samples were collected every 20 minutes and pain intensity was estimated concurrently with a visual analog scale and a categorical rating scale for up to 4 hours after surgery. A significant analgesic effect (P <.01, compared with placebo) was shown for both drugs, with the efficacy of celecoxib being intermediate between ibuprofen and placebo. A similar relationship was observed for the suppression of prostaglandin E(2) (a product of both isoforms) at time points consistent with COX-2 expression (P <.001). Ibuprofen consistently suppressed thromboxane B(2) (a product of COX-1) levels at all time points (P <.05), whereas the effect of celecoxib did not differ from that of placebo. The suppression of products of COX-2 coincident with pain suppression and the absence of COX-1 inhibition suggest that celecoxib is a relatively selective COX-2 inhibitor in vivo.

Therapeutic uses of non-steroidal anti-inflammatory drugs in dentistry.

The non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used classes of drugs for the management of acute and chronic pain in dentistry. Their therapeutic efficacy and toxicity are well-documented and provide evidence that NSAIDs generally provide an acceptable therapeutic ratio of pain relief with fewer adverse effects than the opioid-mild analgesic combination drugs that they have largely replaced for most dental applications. The great many studies done with the oral surgery model of acute pain indicate that a single dose of an NSAID is more effective than combinations of aspirin or acetaminophen plus an opioid, with fewer side-effects, thus making it preferable for ambulatory patients. The combination of an NSAID with an opioid generally results in marginal analgesic activity but with an increased incidence of side-effects, which limits its use to patients in whom the NSAID alone results in inadequate analgesia. The selective COX-2 inhibitors hold promise for clinical efficacy with less toxicity from chronic administration and may prove advantageous for the relief of chronic orofacial pain. The use of repeated doses of NSAIDs for chronic orofacial pain should be re-evaluated in light of a lack of documented efficacy and the potential for serious gastrointestinal and renal toxicity with repeated dosing.

Additive analgesic effects of oxycodone and ibuprofen in the oral surgery model

Purpose: A traditional approach to achieve greater analgesic efficacy is to combine an efficacious dose of a nonopioid with a dose of an opioid sufficient to produce additive analgesia without a substantial increase in the incidence of adverse effects. This study evaluated the additive analagesic effects of the combination of ibuprofen and oxycodone. Patients and Methods: A dose of 400 mg ibuprofen was compared with 400 mg ibuprofen with oxycodone in doses of 2.5, 5, or 10 mg in the oral surgery model of acute pain. Analgesic efficacy was measured with category and visual analog scales at 15, 30, 45, and 60 minutes and hourly up to 6 hours. Results: Ibuprofen plus 10 mg oxycodone produced significantly greater analgesia compared with the other three groups, as measured by the visual analog scale from 15 minutes after drug administration up to the 2-hour observation. All four treatments were similar from 3 to 6 hours, with the area under the pain intensity difference curve being similar across groups. Neither the 2.5-mg nor the 5-mg oxycodone dose provided any additive analgesia over ibuprofen at any points. Addition of oxycodone resulted in a dose-related increase in the number of patients reporting adverse effects, with significantly greater drowsiness and vomiting at the 10-mg dose. Conclusions: These results indicate that additive analgesia can be achieved for the combination of a nonsteroidal anti-inflammatory drug and an orally effective opioid, with faster onset of relief for the combination of 400 mg ibuprofen and 10 mg oxycodone over the first 2 hours after administration, but at the expense of an increased incidence of adverse events.

Quantifying analgesic onset in the oral surgery model

Quantifying analgesic onset in the oral surgery model

Antihyperalgesic Effect of the N‐methyl‐D‐aspartate Receptor Antagonist Dextromethorphan in the Oral Surgery Model

Peripheral neuronal barrage from tissue injury produces central nervous system hyperexcitability through the activation of N-methyl-D-aspartate (NMDA) receptor sites by excitatory amino acids and neuropeptides. This study evaluated if attenuation of NMDA receptor activation with dextromethorphan (DM) suppresses the postoperative development of hyperalgesia. Seventy-five patients undergoing oral surgery in a parallel-group, double-blind study randomly received either a placebo or the maximally tolerated dose of DM administered orally prior to and continuing for 48 hours following surgery. Pain as measured by category, visual analog, and verbal descriptor scales was not significantly different between groups during the first 6 hours following surgery. However, pain at 48 hours was decreased in the DM group as measured by scales for pain intensity and unpleasantness. Subjects in the DM group also self-administered fewer acetaminophen tablets for unrelieved pain over 24 to 48 hours postoperatively. The results suggest that DM at maximally tolerated doses does not produce an analgesic effect in the immediate postoperative period but reduces pain at 48 hours. This may be related to antagonism of NMDA receptors necessary for the expression of hyperalgesia associated with noxious afferent input postoperatively.

Evaluation of a Neurokinin1 antagonist, CP-99,994, in comparison to ibuprofen and placebo in the oral surgery model.

Evaluation of a Neurokinin1 antagonist, CP-99,994, in comparison to ibuprofen and placebo in the oral surgery model.

Comparison of oral triazolam and nitrous oxide with placebo and intravenous diazepam for outpatient premedication

Triazolam was evaluated as an oral sedative agent for dental outpatients in two studies in the oral surgery model. The first study demonstrated that 0.25 mg of triazolam in combination with nitrous oxide provides therapeutic effects but with a more rapid recovery than a 0.50 mg dose in combination with nitrous oxide. In the second study, triazolam produced a significant anxiolytic effect that was comparable to the effects of diazepam titrated to the usual clinical endpoint (mean dose = 19.3 mg). Less impairment in cognitive-psychomotor impairment and ambulatory function was seen after triazolam in comparison with diazepam. Triazolam appears to be a safe, effective alternative to parenteral sedation with a benzodiazepine for dental outpatients.

Comparison of nonsteroidal anti-inflammatory drugs, ibuprofen and flurbiprofen, with methylprednisolone and placebo for acute pain, swelling, and trismus

Pain, swelling, loss of function, and hyperthermia are acute postoperative sequelae of inflammation due to tissue injury during surgical procedures. Pharmacologic strategies for minimizing the clinical manifestations of surgical trauma are often directed toward blocking the formation or inhibiting the effects of the biochemical mediators of acute inflammation. This study compared two nonsteroidal anti-inflammatory drugs (NSAIDs), flurbiprofen and ibuprofen, with a prototype glucocorticoid, methylprednisolone, in two replicate placebo-controlled studies for suppression of inflammation due to the surgical removal of impacted third molars. The results indicate that NSAIDs produce greater initial analgesia than do steroids, whereas steroids result in greater suppression of swelling and less loss of function. Examination of the pooled data from the two studies indicates that NSAID pretreatment results in a modest suppression of swelling in comparison with placebo. These data suggest that the acute analgesic effects of NSAIDs in the oral surgery model are due to suppression of a nociceptive process, presumably prostaglandin formation, rather than a generalized anti-inflammatory effect.