Intrinsic regulation of CGRP release by dental pulp sympathetic fibers.

Neurotransmission from sympathetic and peptidergic afferent fibers participates in the regulation of pulpal blood flow (PBF) via opposing effects. In this study, we directly tested the hypothesis that activation of pulpal sympathetic terminals inhibits exocytosis of immunoreactive calcitonin gene-related peptide (iCGRP) from peptidergic afferents innervating bovine dental pulp. The results demonstrate that norepinephrine inhibits capsaicin-evoked iCGRP release. The application of alpha-adrenergic antagonists (phentolamine or phenoxybenzamine) increased spontaneous release of iCGRP. Moreover, administration of agents that evoke the release of sympathetic neurotransmitters (guanethidine or reserpine) inhibited capsaicin-evoked iCGRP release. Collectively, these results indicate that sympathetic neurotransmission inhibits exocytosis from pulpal peptidergic afferent fibers. Analysis of these data supports the hypothesis that peripheral sympathetic vasomotor control may operate by a direct mechanism (vasoconstriction) as well as by an indirect mechanism (e.g., inhibition of exocytosis from afferent fibers). Since capsaicin-sensitive neurons are nociceptors, it is possible that certain sympathetic neurotransmission may modulate pain.

beta 2-Adrenoceptor regulation of CGRP release from capsaicin-sensitive neurons.

Previous studies have suggested that neurotransmitter substances from the sympatho-adrenomedullary system regulate pulpal blood flow (PBF), in part, by the inhibition of vasoactive neuropeptide release from pulpal sensory neurons. However, no study has evaluated the role of beta-adrenoceptors. We evaluated the hypothesis that activation of beta-adrenoceptors inhibits immunoreactive calcitonin gene-related peptide (iCGRP) release from capsaicin-sensitive nociceptive neurons via in vitro superfusion of bovine dental pulp. Either norepinephrine or epinephrine inhibited capsaicin-evoked iCGRP. The norepinephrine effect was blocked by the selective beta(2)-adrenoceptor antagonist, ICI 118,551, but not by pre-treatment with the selective beta(1)-adrenoceptor antagonist, atenolol. In addition, application of albuterol, a selective beta(2)-adrenoceptor agonist, significantly blocked capsaicin-evoked release of iCGRP. Collectively, these studies demonstrate that activation of beta(2)-adrenoceptors in dental pulp significantly reduces exocytosis of neuropeptides from capsaicin-sensitive nociceptors. This effect may have physiologic significance in regulating PBF. Moreover, since capsaicin selectively activates nociceptors, beta(2)-adrenoceptor agonists may have clinical utility as peripherally acting therapeutics for dental pain and inflammation.

A longitudinal evaluation of pulpal pain during orthodontic tooth movement.

OBJECTIVES: To examine the longitudinal changes in pulpal sensitivity to electrical stimulation and the relationship to pulpal sensitivity as measured by electrical stimulation and subjective reports of tooth pain after archwire insertion. DESIGN: Non-randomized, prospective trial, with matched controls. SETTING AND SAMPLE POPULATION: Regional Clinical Dental Research Center at the University of Washington School of Dentistry. Eighteen adult subjects of age 13-37 years. Nine experimental subjects planned for orthodontic treatment. Nine control subjects matched for gender and age who did not have orthodontic treatment. EXPERIMENTAL VARIABLE: Fixed orthodontic appliances and initial archwire placement in experimental subjects compared with 'no treatment' control subjects. OUTCOME MEASURE: Subjective assessments of orthodontic tooth pain were made using visual analogue scales. Electrically evoked detection and pain thresholds were determined using a computer-controlled tooth stimulator. Data were gathered at five time points: after bracket placement (baseline), 1 h after placement of initial archwires, 1 day after archwire placement, 1 week after archwire placement, and 1 month after archwire placement. Comparable time intervals were used for the 'no treatment' control subjects. RESULTS: Subjective ratings of treatment-evoked tooth pain in the experimental group were the greatest at the post-archwire day 1 observation and progressively decreased for the remaining observations. Control subjects reported little pain at any of these observation times. The detection and pain threshold changes from baseline showed no statistical differences over time or between groups. While not statistically significant, a trend was noted where reports of greater orthodontic tooth pain were associated with increased sensitivity to electrical stimulation (i.e. lower detection and pain thresholds). CONCLUSION: Orthodontic patients experience significant pain and discomfort 1 day after initial archwire placement (i.e. activation). Future research should investigate whether self-reports of treatment-evoked tooth pain intensity are associated with pulpal sensitivity.

Pressure-pain thresholds and MRI effusions in TMJ arthralgia.

It has been suggested that MRI-depicted effusions identify patients with TMJ arthralgia. The Research Diagnostic Criteria (RDC) propose a pressure-pain threshold (PPT) of 1 pound for the identification of TMJ arthralgia. The hypotheses in this study were that: (1) there is no association between MRI-depicted effusions and TMJ arthralgia, and (2) a PPT of 1 pound does not discriminate between subjects with and those without arthralgia. Thirty females with TMJ disc displacement with reduction were divided into two groups based on the presence or absence of the self-report of TMJ pain. Bilateral TMJ PPTs and MRIs were obtained. Increasing palpation pressure from 1 to 3 pounds increased the sensitivity for identifying arthralgia from 22% to 100%, with a corresponding decrease in the specificity from 100% to 81%. The sensitivity and specificity of effusions for identifying arthralgia were 85% and 28%, respectively. These results suggest that the use of palpation pressures greater than 1 pound is a valid test for TMJ arthralgia. However, TMJ effusions lack adequate specificity for identifying TMJ arthralgia and were not associated with pain.

Activation of excitatory amino acid receptors in bovine dental pulp evokes the release of iCGRP.

The activation of excitatory amino acid (EAA) receptors within the central nervous system is associated with numerous centrally mediated phenomena, including hyperalgesia. However, relatively little is known about the peripheral mechanisms which these receptors may regulate when activated. This research evaluated the hypothesis that EAA receptors in bovine dental pulp activate a population of peptidergic sensory neurons as measured by the release of immunoreactive calcitonin gene-related peptide (iCGRP), a neuropeptide associated with neurogenic inflammation. In vitro superfusion of bovine dental pulp was used to evaluate the regulation of iCGRP secretion by the EAA receptor agonists AMPA, kainate, NMDA, and L-glutamate. Both AMPA and kainate stimulated the release of iCGRP in a concentration-dependent manner (AMPA EC50 = 0.27 +/- 3.3 nM; kainate EC50 = 3.2 +/- 1.1 microM). Pre-treatment and co-administration of the AMPA/kainate receptor antagonist CNQX significantly reduced the iCGRP release evoked by either of these agonists. In contrast, neither NMDA nor L-glutamate induced any consistent changes in iCGRP release. These results suggest that the activation of AMPA and kainate receptors in dental pulp may contribute to peripheral release of vasoactive neuropeptides which mediate a neurogenic component of inflammation.

Tramadol hydrochloride: analgesic efficacy compared with codeine, aspirin with codeine, and placebo after dental extraction.

Tramadol hydrochloride is a novel, centrally acting analgesic with two complementary mechanisms of action: opioid and aminergic. Relative to codeine, tramadol has similar analgesic properties but may have fewer constipating, euphoric, and respiratory depressant effects. A two-center randomized double-blind controlled clinical trial was performed to assess the analgesic efficacy and reported side effects of tramadol 100 mg, tramadol 50 mg, codeine 60 mg, aspirin (ASA) 650 mg with codeine 60 mg, and placebo. Using a third molar extraction pain model, 200 healthy subjects were enrolled in a 6-hour evaluation after a single dose of drug. Of the 200 patients enrolled, seven provided incomplete efficacy data or discontinued prematurely and one was lost to follow-up. Using standard measures of analgesia, including total pain relief score (TOTPAR), maximum pain relief score (MaxPAR), sum of pain intensity difference scores (SPID), peak pain intensity difference (Peak PID), remedication, and global evaluations, all active treatments were found to be numerically superior to placebo. ASA/codeine was found to be statistically superior to placebo for all measures of efficacy. Tramadol 100 mg was statistically superior to placebo for TOTPAR, SPID, and time of remedication, whereas tramadol 50 mg was statistically superior to placebo onlyfor remedication time. Codeine was not found to be statistically superior to placebo for any efficacy measure. A greater TOTPAR response compared with all other active measures was seen for ASA/codeine during the first 3 hours of study. The 6-hour TOTPAR scores for the tramadol groups and ASA/ codeine group were not significantly different. Gastrointestinal side effects (nausea, dysphagia, vomiting) were reported more frequently with tramadol 100 mg, ASA/ codeine, and codeine 60 mg than with placebo.

Racial differences on the Conners Teacher Rating Scale.

Factor congruence and mean differences on the Conners Teacher Rating Scale were assessed across African-American and Caucasian school children. Factor analyses conducted separately by gender revealed similar factors across races for males and females. The main differences in factor structure within gender were the presence of an Antisocial factor in black males and an Inattention factor in white females. Across both males and females, teachers tended to rate black children higher than white children on factors relating to externalizing behaviors. Whether mean differences are a result of teacher bias or actual behavioral differences in the classroom needs further research.

Delayed diagnosis of a glenohumeral joint dislocation in a child with developmental delay.

Glenohumeral joint dislocations rarely occur in children. Those that have been reported have all been reduced in a closed fashion. With the exception of one, there have not been any comorbidities in the children that would have led to a delay in diagnosis. To the best of our knowledge, we report the first case of a child with a delayed diagnosis of an anterior dislocation of the glenohumeral joint that required an open reduction. In a child with other medical problems, especially developmental delay, who may have difficulty expressing his symptoms, early detection and intervention are crucial and may obviate the need for open reduction of the dislocated and painful glenohumeral joint.

Multidrug intravenous sedation: determinants of the sedative dose of midazolam.

OBJECTIVES: The efficacy of multidrug intravenous sedation regimens in oral surgery is based on the ability to titrate opioids, benzodiazepines, and barbiturates to a desired level of relaxation. Dosage requirements to reach the initial sedation end points of slurred speech and ptosis of eyelids vary widely from one patient to another. STUDY DESIGN: An assessment of physical, cardiovascular, behavioral, and pharmacologic factors that might predict midazolam dosage requirements for the initial sedation titration was carried out with data collected from a large controlled clinical trial of fentanyl, midazolam, and methohexital sedation for third molar surgery. RESULTS: Dosage requirements for the initial titration of midazolam were found to be significantly higher when fentanyl was not included in the sedation regimen and when presedation heart rate and presedation systolic blood pressure were elevated.

Catecholamine-Containing Cells in Larval and Postlarval Bivalve Molluscs.

Previous studies have suggested an involvement of catecholamines in the control of several larval behaviors, such as feeding, locomotion, and induction of settling and metamorphosis. In the present study we employed aldehyde-induced, blue-green fluorescence to indicate catecholamines in cells within representatives of two bivalve families, the Pectinidae (Placopecten magellanicus) and the Mytilidae (Mytilus edulis). Larvae were examined at different stages of development before and also shortly after settlement. The general distribution of fluorescent cells was similar in the two species. By midveliger stage, several fluorescent cells and fibers were located along the outer rim of each velar lobe, and a pair of flask-shaped cells was located lateral to the mouth. A single fiber from near the mouth projected to a region beneath the apical tuft. In the pediveliger, the cells by the mouth were joined by an additional two to four fluorescent cells. The developing foot also contained numerous such cells, some of which had processes that penetrated the epithelium on the "sole" and bore ciliated terminals. Fluorescent somata were also located around the edge of the mantle. Centrally projecting fibers appeared to terminate in the pedal and abdominal ganglia, which also contained a few fluorescent somata. After settlement, the velar lobes and resident fluorescent somata disappeared, but fluorescent cells in the foot persisted as this latter organ grew. Fluorescent cells within the developing gill were connected with the abdominal ganglia by means of fibers. Control preparations labeled with antibodies raised against serotonin indicated that the aldehyde-induced fluorescence was not due to the presence of indoleamines. The present study not only confirms previous chromatographic evidence suggesting the presence of catecholamines in the larvae of bivalve molluscs, but also identifies putative neuronal circuits that may control various larval behaviors.

Electrodiagnostic study of carpal tunnel syndrome in wheelchair basketball players.

UNLABELLED: OBJECTIVE-DESIGN-SUBJECTS: Compression neuropathies are common injuries about the wrist in wheelchair athletes. Thirty-three world-class wheelchair basketball players were studied electrodiagnostically to determine the prevalence and severity of median neuropathy at the wrist in these athletes. RESULTS: Thirty percent of these athletes had symptoms consistent with carpal tunnel syndrome (CTS), and 70% of these had electrodiagnostic confirmation of this injury. Overall, 52% of the 33 athletes had electrodiagnostic findings of median neuropathy at the wrist with nine athletes (27%) exhibiting bilateral abnormalities. Four athletes (12%) had abnormal electrodiagnostic findings involving the ulnar nerve at the wrist. CONCLUSIONS: This prevalence of CTS in wheelchair basketball players appears to be similar to that found in the general paraplegic population. Early recognition and treatment of CTS in these athletes are recommended to avoid chronic problems.

Laminin overrides the inhibitory effects of peripheral nervous system and central nervous system myelin-derived inhibitors of neurite growth.

Axon growth inhibitory proteins associated with central nervous system (CNS) myelin are responsible in part for the absence of long distance axon regeneration in the adult mammalian CNS. We have recently reported that myelin-associated glycoprotein (MAG), which is also present in peripheral nerves, is a potent inhibitor of neurite growth. This was surprising given the robust regenerative capacity of peripheral nerves. We now provide evidence that myelin purified from peripheral nerve also has neurite growth inhibitory activity. However, this activity can be masked by laminin, which is a constituent of the Schwann cell basal lamina. We also report that laminin, which is largely absent from the normal adult mammalian CNS, when added to purified CNS myelin, can override the neurite growth inhibitory activity in CNS myelin. These results have important implications for the development of strategies to foster axon regeneration in the adult mammalian CNS where multiple growth inhibitors exist.

Glutamate participates in the peripheral modulation of thermal hyperalgesia in rats.

While the effects of excitatory amino acids have been well characterized in the central nervous system, relatively little is known about their possible modulation of elements responsible for hyperalgesia within peripheral tissue. The presented experiments demonstrate that the intraplantar (i.pl.) injection of L-glutamate (30 nmol) evokes a thermal hyperalgesic response in the paw withdrawal latencies of normal rats which is stereospecific. In addition, the i.pl. injection of either the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (10 nmol) or the competitive alpha-amino-3-hydroxy-4-methyl-5-isoxazolepropionic acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)(100 nmol) into hindpaws inflamed with carrageenan significantly reduced the thermal hyperalgesic response in rats. Collectively, these results suggest that excitatory amino acids activate a peripheral target which facilitates a hyperalgesic behavioural response to thermal stimulation via a receptor mediated process.

Suprascapular neuropathy in athletes: case reports.

Shoulder pain and dysfunction is a common problem among athletes, and a great deal of attention is being given to scapular stability and rotator cuff pathology. Two athletes who were first seen with posterolateral shoulder pain and weakness were found to have isolated entrapment of the suprascapular nerve, causing their impairment. Both athletes responded well to conservative treatment, but this entity occasionally requires operative decompression. This article reviews the most common presentation, etiologies, and treatments of suprascapular neuropathy and how it can affect athletic performance.

Pharmacology of peripheral neuropeptide and inflammatory mediator release.

Research conducted in the last 10 years has increased our knowledge on pain mechanisms substantially. Although many local tissue mediators, including neuropeptides, are known to exert pro-inflammatory effects, comparatively little is known about the actual tissue levels of these inflammatory mediators and their pharmacologic regulation. This article describes two new methods, clinical microdialysis and superfusion of dental pulp, which provide data on the pharmacology of peripheral neuropeptide and inflammatory mediator release. Collectively, these methods provide a biochemically based approach toward determining the mechanisms and management of orofacial pain.