Biomedical subjects

William Maixner

Publications and source records attributed to William Maixner.

14 recordsLinked to original sources

PubMed2003

Repeated swim stress increases pain-induced expression of c-Fos in the rat lumbar cord.

We have previously demonstrated that repeated swim stress produces a long-lasting cutaneous hyperalgesia in rats. We have now looked at c-Fos expression in the spinal lumbar cord of male Sprague-Dawley rats subjected to 10-20 min daily sessions of forced swimming for 3 consecutive days. Control rats were subjected to sham swimming or were completely naive. Forty-eight hours later, nociception was assessed by recording for 90 min the nociceptive behavior evoked the injection of 1% formalin in the hind paw. Thirty min later, the rats' spinal cords were removed for c-Fos immunocytochemistry. Total pain scores were 45% higher in swim stressed rats compared to control animals due an increased nociceptive behavior during last 70 min of the recording period. In addition, the number of c-Fos-immunoreactive nuclei was 40% higher in the lumbar ipsilateral dorsal horn (L4-L5) of swim stressed rats than in controls, being the highest relative increase, relative to the control groups, observed in laminae III-IV, followed by laminae V-VI, with the smallest difference in laminae I-II. c-Fos expression in the contralateral dorsal horn was higher in swim stressed rats than in sham and nai;ve rats. In the absence of a nociceptive stimulus, a low level of c-Fos expression was observed mainly in laminae I, II, V, and VI, being higher in swim stressed rats than in sham rats. These findings suggest that repeated inescapable and uncontrollable stress could induce a sensitization and activation of sensory neurons at the spinal level.

Animals↗

PubMed2003

Reduction of TMD pain by high-frequency vibration: a spatial and temporal analysis.

Under some conditions, vibration delivered to the skin can reduce pain (vibratory analgesia). Previous studies of this phenomenon in a clinical context have been somewhat variable in terms of stimulus control, and have not examined the way in which the spatial distribution of pain is affected. In the present study, we used rigorously controlled conditions to examine vibratory analgesia in participants (N=17) with painful temporomandibular disorders (TMD). Results of 20- and 100-Hz vibration were compared with data from a no-vibration control condition. The results document for the first time that vibratory analgesia occurs in TMD chronic pain conditions. We measured its time course using continuous visual analog scale (VAS) recording, and its spatial aspects by asking subjects to indicate painful regions on standardized drawings. VAS ratings and drawings both showed that pain is reduced by 100-Hz, but not by 20-Hz, vibration. The effectiveness of the high-frequency vibration cannot be attributed to a mechanism involving Pacinian corpuscles, since these receptors are lacking in the skin of the orofacial region. Spatial analyses revealed that ipsilateral and contralateral effects of vibration were statistically equivalent, suggesting that vibratory analgesia relies at least in part on central nervous system processes rather than local mechanisms.

Adolescent↗

PubMed2002

Group differences in pain modulation: pain-free women compared to pain-free men and to women with TMD.

Previously reported differences in sensitivity to experimental pain stimuli between the sexes, as well as between temporomandibular disorder (TMD) patients and healthy control subjects, may be attributable in part to group differences in two pain modulatory mechanisms: the baroreceptor reflex arc and the endogenous opioid system. Twenty-two pain-free (PF) men, 20 PF women and 20 women with TMD underwent two testing sessions in which heat pain and ischemic arm pain threshold and tolerance were measured during both sessions, but followed relaxation during one session and laboratory stress tasks during the other. Blood pressure (BP) and plasma -endorphin (E) concentration were measured during a baseline rest and during the stress or relaxation periods. PF men's threshold and tolerance for heat pain, but not for ischemic pain, exceeded that of PF women's during both sessions. PF women and TMD women did not differ in sensitivity to either pain modality; however, significantly lower ischemic pain threshold (IPTh) was linked to oral contraceptive use in PF women but not TMD patients. In the men alone, higher baseline systolic BP (SBP) was correlated with higher heat pain threshold on both days and heat pain tolerance on the stress day. Conversely, in TMD women, higher baseline SBP was correlated with lower ischemic pain tolerance (IPTol) on both days; BP and pain sensitivity were not related in PF women. In men, but not in PF or TMD women, stress systolic and diastolic BP were positively correlated with heat pain threshold and tolerance and higher diastolic reactivity to stress were correlated with higher heat pain and IPTh and tolerance. On the stress day, higher baseline E level was strongly associated with higher IPTol in PF women but marginally associated with lower IPTol in TMD women. Thus, it appears that a BP-related analgesic mechanism (probably baroreceptor-mediated) predominates in PF men, while an endogenous opioid mechanism predominates in PF women. Stress enhances the expression of these central mechanisms. Female TMDs appear unable to effectively engage normal pain-inhibitory systems; opioid receptor desensitization and/or downregulation are probably implicated, because TMDs' production of E appears normal.

Adult↗

PubMed2002

Trigeminal c-Fos expression and behavioral responses to pulpal inflammation in ferrets.

Injury to peripheral dental tissues evokes dynamic alternations in central sensory pathways. We have previously reported that transient stimulation of the dental pulp with noxious heat evokes the induction of the immediate early gene product Fos in the transitional region between subnucleus interpolaris and caudalis (Vi/Vc) and subnucleus caudalis (Vc). A question arises as to whether similar changes occur in response to inflammation to the tooth pulp. In this study, the effects of pulpal inflammation produced by bacterial lipopolysaccharide (LPS) on face-grooming behavior and trigeminal Fos expression were examined. Face-grooming behaviors were recorded daily for 3 days pre- and 24, 48 and 72 h post- LPS or saline application. All animals were perfused 72 h post- LPS or saline application. Brainstems were processed for Fos-like immunoreactivity (Fos-LI). Teeth were processed for H&E staining. Histological examination of LPS-treated teeth revealed features of an acute pulpitis. Moreover, LPS-treated animals showed greater face-grooming activity (i.e. tongue protrusions) directed to the injured tooth than the sham-operated group. The number of Fos-positive neurons was greater in the trigeminal subnucleus caudalis (Vc) and the transitional regions (Vi/Vc) in LPS-treated animals compared with sham-operated animals, and greater in the deeper laminae than the superficial laminae of each trigeminal region. LPS treatment did not evoke Fos expression in the rostral trigeminal regions above Vi/Vc. These results demonstrate that LPS-induced pulpal inflammation results in significant alterations in the Vi/Vc and Vc, and such changes may underlie the observed nociceptive behavioral responses and may play an important role in producing a symptomatic pulpitis in humans.

Animals↗

PubMed2002

Temporomandibular disorder and optimism: relationships to ischemic pain sensitivity and interleukin-6.

The current study examined patients with temporomandibular disorders (TMD) (n=20) and pain-free controls (n=28) under stress and relaxation conditions. Interleukin-6 (IL-6), norepinephrine and epinephrine (NE and E) were measured both before and during each of two conditions: a non-stressful relaxation period and a speech stressor. Ischemic pain sensitivity was also assessed after each of these conditions. Optimism (Life Orientation Test (LOT)), which has been associated with better outcomes in relationship to health and disease, was also evaluated in relationship to ischemic pain tolerance and unpleasantness ratings as well as to IL-6 levels under the two conditions. Regression analysis determined the unique contribution of each predictor and the interaction between Optimism and Group (TMD versus controls) after controlling for gender and blood pressure. During stress, IL-6 levels appeared to parallel NE with only controls displaying significant increases. After controlling for depressed mood, TMD patients as a whole showed a significantly blunted response in IL-6 levels produced during stress as compared to controls (beta=0.31*). Although TMD subjects as a whole did not show the expected greater pain sensitivity to the ischemic task, those displaying a less optimistic style did exhibit lower pain tolerance times (beta=-0.61*) and higher pain unpleasantness ratings (beta=0.48*), compared with low optimism controls and high optimism TMD patients. Less optimistic TMD patients also had higher NE and IL-6 levels during stress than other TMD patients, while optimism was unrelated to responses in controls (*P<0.05).

Adult↗

PubMed2002

4.1 Web-based interactive learning programmes.

In the future, the training of competent dentists will need to take advantage of up-to-date digital technologies and learning practices. In order to accomplish this, the following goals should be considered: i) the design of 'customizable' web-based curriculum matrices that accommodate the training philosophies and resources of individual dental schools; ii) the development of digital instructional modules that can be incorporated or downloaded into specific parts of a curriculum; iii) the establishment of an e-consortium, which provides peer view and guidance in the design of teaching modules, and which is responsible for the storage, maintenance, and distribution of teaching modules within the consortium; iv) the development of central human and physical resources at each dental school to enable the seamless delivery of instructional modules in a variety of learning environments; and v) the assessment and provision of ICT training to students and faculty with respect to the use of computers and related digital technologies and educational software programmes. These goals should lead to the creation of a 'virtual dental school'. Within this project summative and formative evaluations should be performed during both the production and development of teaching material (e-learning material) and the learning process. During the learning process the following aspects should be measured and evaluated: i) students' behaviour; and ii) effectiveness, retention and the transfer of e-learned material into the clinical situation. To obtain evidence of the efficacy of e-learning material a certain amount of research has to be done in the near future. It is suggested that all parameters currently known have to be implemented during the development of a learning programme. Previous workers have evaluated the following elements with e-learning: i) planning, ii) programming and technical development, iii) learning behaviours, iv) learning outcomes of both the programme and the student, v) the acquisition of knowledge, skills and attitude and vi) the transfer of e-learned skills into clinical situations.

Competency-Based Education↗

PubMed2002

Menstrual cycle, beta-endorphins, and pain sensitivity in premenstrual dysphoric disorder.

This study examined pain sensitivity and pain modularity mechanisms (e.g., beta-endorphin levels, blood pressure) in women with premenstrual dysphoric disorder (PMDD; n = 27) and healthy controls (n = 27) during the follicular and luteal phases of the menstrual cycle. Physiological measures were taken during rest and ischemic pain testing. In both cycle phases, PMDD women (a) displayed lower resting cortisol and beta-endorphin levels and (b) exhibited shorter pain threshold and tolerance times and greater pain unpleasantness ratings during pain. PMDD women also reported greater pain unpleasantness and intensity and had lower beta-endorphin levels in their luteal phase and tended to display higher blood pressure levels at rest and during pain testing. Results suggest that endogenous opioids may be pathophysiologically relevant to PMDD and that the hypothalamic-pituitary-gonadal axis may modulate pain sensitivity in PMDD.

Adult↗

PubMed1999

The effect of fentanyl on c-fos expression in the trigeminal brainstem complex produced by pulpal heat stimulation in the ferret.

We have previously shown that Fos-like immunoreactivity (Fos-LI) is evoked in the brainstem of ferrets following stimulation of pulpal A delta and C fibers originating from the maxillary canine. This study evaluated the effects of the mu-opioid receptor agonist fentanyl on Fos expression evoked by noxious thermal stimulation of the right maxillary and mandibular canines in pentobarbital/chloral hydrate anesthetized adult male ferrets. Pulpal heating evoked Fos expression in two distinct regions of the spinal trigeminal nuclear complex: the transitional region between subnucleus interpolaris and caudalis (Vi/Vc) and within the subnucleus caudalis (Vc). More Fos positive cells were expressed in both regions ipsilateral to the site of stimulation compared with the contralateral side (P < 0.05, ANOVA). Pretreatment with fentanyl significantly and dose-dependently suppressed the number of Fos positive cells in both the Vi/Vc transitional region and Vc (P < 0.05, ANOVA). The suppressive effect of fentanyl on Fos expression was blocked by the intravenous administration of naloxone, an opioid antagonist, indicating a specific opioid receptor effect. In addition, opioid receptor antagonism with naloxone alone enhanced Fos expression in Vi/Vc and Vc in response to heat stimulation. The administration of naloxone without heat stimulation failed to evoke Fos expression in Vi/ Vc and Vc. These findings suggest that the activation of trigeminal Vi/Vc and Vc neurons by noxious dental heat stimulation is controlled by a naloxone sensitive endogenous opioid system as indicated by Fos expression. Collectively, these results suggest that neuronal populations in Vi/Vc and Vc regions may contribute to pain responses to noxious dental stimulation and these responses can be modulated by both endogenous and exogenous opioids.

Analgesics, Opioid↗

PubMed1998

Sex differences in temporal summation but not sensory-discriminative processing of thermal pain.

Gender differences in experimental pain sensitivity have been widely investigated, and the results generally indicate that females exhibit greater sensitivity to noxious stimuli than males. However, results using thermal pain procedures have been inconsistent, with some studies reporting greater responses among females and other studies reporting no gender differences. The present study investigated gender differences in thermal pain perception using several different psychophysical procedures. Twenty-seven females and 22 males underwent thermal testing, including: determination of thermal pain threshold and tolerance, a thermal discrimination procedure, real-time magnitude estimates of heat pulses, and temporal summation of thermal pain. The results indicated lower thermal pain threshold and tolerance and greater temporal summation of thermal pain among females, but no gender differences in thermal discrimination or real-time magnitude estimates of discrete heat pulses. These findings suggest that gender differences in thermal pain perception may be more robust for sustained, temporally dynamic thermal stimuli with a strong C-fiber component.

Adult↗

PubMed1998

Generalized vibrotactile allodynia in a patient with temporomandibular disorder.

This report presents the findings from a psychophysical study of vibrotactile responses in a patient diagnosed with temporomandibular disorder (TMD). This patient unexpectedly reported pain due to innocuous vibrotactile stimulation, and this allodynia appeared to have a component of temporal summation. The pain response occurred not only in the region of the clinical pain (the face), but also on the volar forearm, where the patient reported no clinical pain. Administration of the N-methyl-D-aspartate (NMDA) receptor antagonist dextromethorphan (DM), but not vehicle, attenuated the vibration-induced pain at both sites.

Adult↗

PubMed1995

Sensitivity of patients with painful temporomandibular disorders to experimentally evoked pain.

Temporomandibular disorders (TMD) represent a group of chronic painful conditions involving the muscles of mastication and the temporomandibular joint. We determined whether patients with painful TMD are more sensitive to noxious stimuli than age-matched control subjects. Fifty-two TMD patients (16 with muscle pain and 36 with combined muscle and joint pain) and 23 age-matched and gender-matched volunteers participated. Forearm thermal pain threshold and tolerance values were determined. A submaximal effort tourniquet procedure was used to evoke ischemic muscle pain. Relative to control subjects, TMD patients had significantly lower thermal pain threshold, ischemic pain threshold, and ischemic pain tolerance values; and thermal pain tolerance values also tended to be lower. Pain sensitivity did not differ between the two groups of TMD patients. Furthermore, the submaximal effort tourniquet procedure, which is capable of altering acute orofacial pain (Sigurdsson and Maixner, 1994) did not produce a consistent reduction in orofacial pain associated with TMD. We concluded that TMD patients are more sensitive to noxious stimuli than pain-free controls. These findings provide additional evidence that TMD is a psychophysiological disorder of the central nervous system which modulates emotional, physiological and neuroendocrine responses to emotional and physical stressors.

Adolescent↗

PubMed1994

Effects of experimental and clinical noxious counterirritants on pain perception.

It is commonly accepted that application of a sustained noxious stimulus frequently suppresses the perception of pain. In this investigation, we have determined whether painful forearm ischemia suppresses tooth pain resulting from an acute irreversible pulpitis. We have also determined whether the physiological responses to toothache alter the perception of pain evoked by experimental procedures. Ten male subjects experiencing a painful toothache (group TA) and 7 age-matched pain-free male subjects (group PF) participated in these studies. During session 1, heat pain threshold and tolerance values were determined for both groups. The times to ischemic pain onset and ischemic pain tolerance were determined for both groups using the submaximal effort tourniquet procedure. The effect of the tourniquet procedure on the intensity, unpleasantness, and spatial distribution of toothache was also assessed. Session 2 was conducted on 7 TA and 7 PF subjects 1 week later and was conducted like session 1 with the exception that group TA was not experiencing tooth pain during this session. Measures of thermal pain perception and forearm ischemic pain perception were not altered by the occurrence of toothache. In contrast, sustained noxious forearm ischemia produced a marked reduction in the intensity, unpleasantness and spatial distribution of pulpal pain. These effects on pulpal pain remained for at least 5 min after removal of the tourniquet while the arm was pain free. These findings suggest that a noxious conditioning stimulus does not universally inhibit pain perception but instead depends on unidentified interactions between the noxious test and conditioning stimuli.

Acute Disease↗

PubMed1992

Sensitizing effects of leukotriene B4 on intradental primary afferents.

Previous studies have established that leukotriene B4 (LTB4) sensitizes cutaneous nociceptors. In this study the effects of LTB4 on spontaneous and stimulus-evoked nerve activity from primary afferents innervating the dentin of canines in adult cats were examined. LTB4 treatment (25 micrograms/ml) significantly enhanced stimulus-evoked intradental nerve activity (INA) for at least 20 min after the removal of the compound from the recording preparation. Teeth treated with LTB4 demonstrated enhanced spontaneous nerve activity following the removal of hypertonic saline used to evoked INA. These findings provide additional evidence that LTB4 is able to sensitize nociceptors and may be a long-lasting hyperalgesic factor which may contribute to pain of pulpal origin.

Animals↗

PubMed1992

Systemic morphine administration attenuates the perceived intensity of noxious heat in the monkey.

We examined the ability of systemic morphine to diminish the sensory discriminative features of noxious heating. Monkeys were trained to perform a thermal detection task, and the time until their detection of small increases in heating was used as a measure of the perceived intensity of pain. Relatively small doses of morphine sulfate (0.1, 0.3 and 1.0 mg/kg, i.m.) increased the time until detection of graded temperature increases (0.4-1.0 degrees C) from a noxious 46 degrees C baseline. These effects were generally dose-dependent, reversed by systemic naloxone, and did not result from changes in attentional, motivational or motoric aspects of the monkeys' behavior. Furthermore, the effects of morphine were more pronounced on detection of temperature shifts that were near threshold. These findings indicate that doses of morphine in the therapeutic dose range for humans alter the perceived intensity of noxious heat in monkeys.

Animals↗