Sharon M. Gordon

Coaggregation-Mediated Interactions of Streptococci and Actinomyces Detected in Initial Human Dental Plaque

Streptococci and actinomyces that initiate colonization of the tooth surface frequently coaggregate with each other as well as with other oral bacteria. These observations have led to the hypothesis that interbacterial adhesion influences spatiotemporal development of plaque. To assess the role of such interactions in oral biofilm formation in vivo, antibodies directed against bacterial surface components that mediate coaggregation interactions were used as direct immunofluorescent probes in conjunction with laser confocal microscopy to determine the distribution and spatial arrangement of bacteria within intact human plaque formed on retrievable enamel chips. In intrageneric coaggregation, streptococci such as Streptococcus gordonii DL1 recognize receptor polysaccharides (RPS) borne on other streptococci such as Streptococcus oralis 34. To define potentially interactive subsets of streptococci in the developing plaque, an antibody against RPS (anti-RPS) was used together with an antibody against S. gordonii DL1 (anti-DL1). These antibodies reacted primarily with single cells in 4-h-old plaque and with mixed-species microcolonies in 8-h-old plaque. Anti-RPS-reactive bacteria frequently formed microcolonies with anti-DL1-reactive bacteria and with other bacteria distinguished by general nucleic acid stains. In intergeneric coaggregation between streptococci and actinomyces, type 2 fimbriae of actinomyces recognize RPS on the streptococci. Cells reactive with antibody against type 2 fimbriae of Actinomyces naeslundii T14V (anti-type-2) were much less frequent than either subset of streptococci. However, bacteria reactive with anti-type-2 were seen in intimate association with anti-RPS-reactive cells. These results are the first direct demonstration of coaggregation-mediated interactions during initial plaque accumulation in vivo. Further, these results demonstrate the spatiotemporal development and prevalence of mixed-species communities in early dental plaque.

Blockade of peripheral neuronal barrage reduces postoperative pain

Abstract Peripheral afferent neuronal barrage from tissue injury produces central nervous system hyperexcitability which may contribute to increased postoperative pain. Blockade of afferent neuronal barrage has been reported to reduce pain following some, but not all, types of surgery. This study evaluated whether blockade of sensory input with a long‐acting local anesthetic reduces postoperative pain after the anesthetic effects have dissipated. Forty‐eight patients underwent oral surgery with general anesthesia in a parallel group, double‐blind, placebo‐controlled study. Subjects randomly received either 0.5% bupivacaine or saline intraoral injections, general anesthesia was induced with propofol, a non‐opioid anesthetic, and 2–4 third molars extracted. Subjects were assessed at 24 and 48 h for postoperative pain and analgesic intake. Blood samples were collected at baseline, intraoperatively and at 1‐h intervals postoperatively for measurement of beta‐endorphin as an index of CNS response to nociceptor input. Plasma beta‐endorphin levels increased significantly from baseline to the end of surgery in the saline group in comparison to the bupivacaine group (P<0.05), indicating effective blockade of nociceptor input into the CNS by the local anesthetic. Pain intensity was not significantly different between groups at 24 h. Pain at 48 h was decreased in the bupivacaine group as measured by category scale and graphic rating scales for pain and unpleasantness (P<0.05). Additionally, subjects in the bupivacaine group self‐administered fewer codeine tablets for unrelieved pain over 24–48 h postoperatively (P<0.05). These data support previous animal studies demonstrating that blockade of peripheral nociceptive barrage during and immediately after tissue injury results in decreased pain at later time points. The results suggest that blockade of nociceptive input by administration of a long‐acting local anesthetic decreases the development of central hyperexcitability, resulting in less pain and analgesic intake.

Clinical Findings and Pain Symptoms as Potential Risk Factors for Chronic TMD: Descriptive Data and Empirically Identified Domains from the OPPERA Case-Control Study

Clinical characteristics might be associated with temporomandibular disorders (TMD) because they are antecedent risk factors that increase the likelihood of a healthy person developing the condition or because they represent signs or symptoms of either subclinical or overt TMD. In this baseline case-control study of the multisite Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) project, 1,633 controls and 185 cases with chronic, painful TMD completed questionnaires and received clinical examinations. Odds ratios measuring association between each clinical factor and TMD were computed, with adjustment for study-site as well as age, sex, and race/ethnicity. Compared to controls, TMD cases reported more trauma, greater parafunction, more headaches and other pain disorders, more functional limitation in using the jaw, more nonpain symptoms in the facial area, more temporomandibular joint noises and jaw locking, more neural or sensory medical conditions, and worse overall medical status. They also exhibited on examination reduced jaw mobility, more joint noises, and a greater number of painful masticatory, cervical, and body muscles upon palpation. The results indicated that TMD cases differ substantially from controls across almost all variables assessed. Future analyses of follow-up data will determine whether these clinical characteristics predict increased risk for developing first-onset pain-related TMD PERSPECTIVE: Clinical findings from OPPERAs baseline case-control study indicate significant differences between chronic TMD cases and controls with respect to trauma history, parafunction, other pain disorders, health status, and clinical examination data. Future analyses will examine their contribution to TMD onset.

Peripheral prostanoid levels and nonsteroidal anti-inflammatory drug analgesia : Replicate clinical trials in a tissue injury model

Nonsteroidal anti‐inflammatory drug (NSAID) analgesia is generally attributed to peripheral suppression of cyclooxygenase (COX) enzymes, leading to decreased products of the arachidonic acid cascade. This study evaluated the in vivo relationship between levels of prostanoids at the site of tissue injury and analgesia aftersystemic or local NSAID administration in a clinical model of tissue injury.

Changes in signs and symptoms following temporomandibular joint disc repositioning surgery

Fifty-one subjects with documented intra-articular pathology refractory to non-surgical therapy underwent temporomandibular joint (TMJ) disc repositioning surgery. Following surgery, subjects were evaluated for 6 months to 6 years by clinical examinations and questionnaires at designated times, and by postsurgical joint imaging. Significant decreases were noted in pain (headache, TMJ pain, ear pain, and neck/shoulder pain), the incidence of joint sounds and locking, and the presence of dietary restrictions. However, 35% of the subjects continued to have residual TMJ pain, and a similar percentage continued to need periodic nonsteroidal anti-inflammatory drugs for analgesia. Some degree of dietary restriction remained in approximately 50% of the subjects, and joint sounds persisted in a similar percentage following surgery. Mean mouth opening was improved by 8 mm, although lateral movements were increased by less than 0.5 mm. Surgery did not decrease the occurrence of jaw deviation, and disc position was unchanged in 86% of the joints imaged at an average of 2 years following surgery. Although TMJ disc repositioning surgery significantly improved pain and dysfunction in TMJ surgery patients, the improvement in disc position was not maintained in most subjects following surgery.

Dexamethasone suppresses peripheral prostanoid levels without analgesia in a clinical model of acute inflammation

PURPOSE The therapeutic effects of glucocorticoids are generally attributed to suppression of multiple signaling pathways involved in the inflammatory response leading to decreased levels of inflammatory mediators at the site of injury. This study evaluated the in vivo relationship between levels of prostanoids at the site of tissue injury and analgesia after dexamethasone administration in a clinical model of tissue injury. METHODS Subjects were administered dexamethasone 4 mg or placebo 12 hours and 1 hour before the removal of 2 mandibular third molars. A microdialysis probe was implanted at each surgical site for measurement of immunoreactive prostaglandin E2 (PGE(2)) or immunoreactive thromboxane B(2) (TxB(2)), and pain was measured concurrently. Subjects received either ketorolac 30 mg intravenously or placebo at pain onset. RESULTS PGE(2) was detectable in the first postoperative sample, decreased over the next hour and then increased coincident with the onset of postoperative pain. Administration of dexamethasone suppressed PGE(2) levels in samples collected at pain onset in comparison to placebo and significantly suppressed TxB(2) at the surgical site but without any effect on pain report. Subsequent administration of ketorolac significantly reduced pain while decreasing both PGE(2) and TxB(2) levels at the surgical site. CONCLUSION The lack of an analgesic effect for dexamethasone while reducing both PGE(2) and TxB(2) at the site of injury in comparison to ketorolac analgesia accompanied by greater reductions in levels of these prostanoids suggests that glucocorticoids at this dose do not suppress PGE(2) release sufficiently to attenuate peripheral sensitization of nociceptors after tissue injury.

Attenuation of pain in a randomized trial by suppression of peripheral nociceptive activity in the immediate postoperative period.

Peripheral neuronal barrage from tissue injury produces central nervous system changes that contribute to the maintenance of postoperative pain. The therapeutic approaches to blocking these central changes remain controversial, because previous studies have not differentiated presurgical interventions from those administered after tissue injury, yet before pain onset. In this study, we evaluated the relative contributions of blockade of nociceptive input during surgery or during the immediate postoperative period on pain suppression. Subjects were randomly allocated to one of four groups: preoperative 2% lidocaine, postoperative 0.5% bupivacaine, both, or placebo injections. General anesthesia was induced and third molars extracted. Pain was assessed over 4 h and at 24 and 48 h. The &bgr;-endorphin in blood samples increased twofold during surgery, which is indicative of activation of the peripheral nociceptive barrage in response to painful stimuli. Pain was decreased in the immediate postoperative period in the bupivacaine groups, whereas it increased in the lidocaine group over time. Pain intensity was less 48 h after surgery in the groups whose postoperative pain was blocked by the administration of bupivacaine, but no effect was demonstrated for the preoperative administration of lidocaine alone. These results in the oral surgery pain model suggest that minimizing the peripheral nociceptive barrage during the immediate postoperative period decreases pain at later time periods. In contrast, blocking the intraoperative nociceptive barrage does not appear to contribute significantly to the subsequent reduction in pain.

Clinical orofacial characteristics associated with risk of first-onset TMD: the OPPERA prospective cohort study.

UNLABELLED Case-control studies have documented clinical manifestations of chronic temporomandibular disorder (TMD), whereas clinical predictors of TMD development are largely unknown. We evaluated 41 clinical orofacial characteristics thought to predict first-onset TMD in a prospective cohort study of U.S. adults aged 18 to 44 years. During the median 2.8-year follow-up period, 2,737 people completed quarterly screening questionnaires. Those reporting symptoms were examined and 260 people were identified with first-onset TMD. Univariate and multivariable Cox regression models quantified associations between baseline clinical orofacial measures and TMD incidence. Significant predictors from baseline self-report instruments included oral parafunctions, prior facial pain and its life-impact, temporomandibular joint noises and jaw locking, and nonspecific orofacial symptoms. Significant predictors from the baseline clinical examination were pain on jaw opening and pain from palpation of masticatory, neck, and body muscles. Examiner assessments of temporomandibular joint noise and tooth wear facets did not predict incidence. In multivariable analysis, nonspecific orofacial symptoms, pain from jaw opening, and oral parafunctions predicted TMD incidence. The results indicate that only a few orofacial examination findings influenced TMD incidence, and only to a modest degree. More pronounced influences were found for self-reported symptoms, particularly those that appeared to reflect alterations to systems beyond the masticatory tissues. PERSPECTIVE OPPERAs prospective cohort study identifies predictors of first-onset TMD comprising self-reported orofacial symptoms and examination findings. The results suggest a complex pattern of TMD etiology that is influenced by disorders locally, in masticatory tissues, and systemically, in pain-regulatory systems.

Retrieval of biofilms from the oral cavity.

With the use of the removable stents or bonded enamel piece models with or without a continuous bacterial layer, many in vitro or in vivo studies can be initiated. For example, studies on salivary pellicle formation, surface characteristics of biomaterials as they affect plaque development, antiplaque agents, the dynamics of adhesion of bacteria, interspecies adhesion of bacteria, the colonization of bacteria, the dynamics of bacterial growth in vivo, and the succession of growth in older supragingival plaques can be carried out.

The Differential Effects of Bupivacaine and Lidocaine on Prostaglandin E2 Release, Cyclooxygenase Gene Expression and Pain in a Clinical Pain Model

BACKGROUND:In addition to blocking nociceptive input from surgical sites, long-acting local anesthetics might directly modulate inflammation. In the present study, we describe the proinflammatory effects of bupivacaine on local prostaglandin E2 (PGE2) production and cyclooxygenase (COX) gene expression that increases postoperative pain in human subjects. METHODS:Subjects (n = 114) undergoing extraction of impacted third molars received either 2% lidocaine or 0.5% bupivacaine before surgery and either rofecoxib 50 mg or placebo orally 90 min before surgery and for the following 48 h. Oral mucosal biopsies were taken before surgery and 48 h after surgery. After extraction, a microdialysis probe was placed at the surgical site for PGE2 and thromboxane B2 (TXB2) measurements. RESULTS:The bupivacaine/rofecoxib group reported significantly less pain, as assessed by a visual analog scale, compared with the other three treatment groups over the first 4 h. However, the bupivacaine/placebo group reported significantly more pain at 24 h and PGE2 levels during the first 4 h were significantly higher than the other three treatment groups. Moreover, bupivacaine significantly increased COX-2 gene expression at 48 h as compared with the lidocaine/placebo group. Thromboxane levels were not significantly affected by any of the treatments, indicating that the effects seen were attributable to inhibition of COX-2, but not COX-1. CONCLUSIONS:These results suggest that bupivacaine stimulates COX-2 gene expression after tissue injury, which is associated with higher PGE2 production and pain after the local anesthetic effect dissipates.