FAAH selectively influences placebo effects.

Endogenous opioid and cannabinoid systems are thought to act synergistically regulating antinociceptive and reward mechanisms. To further understand the human implications of the interaction between these two systems, we investigated the role of the common, functional missense variant Pro129Thr of the gene coding fatty acid amide hydrolase (FAAH), the major degrading enzyme of endocannabinoids, on psychophysical and neurotransmitter (dopaminergic, opioid) responses to pain and placebo-induced analgesia in humans. FAAH Pro129/Pro129 homozygotes, who constitute nearly half of the population, reported higher placebo analgesia and more positive affective states immediately and 24 h after placebo administration; no effects on pain report in the absence of placebo were observed. Pro129/Pro129 homozygotes also showed greater placebo-induced µ-opioid, but not D(2/3) dopaminergic, enhancements in neurotransmission in regions known involved in placebo effects. These results show that a common genetic variation affecting the function of the cannabinoid system is serving as a probe to demonstrate the involvement of cannabinoid and opioid transmitters on the formation of placebo effects.

Trends in Scope of Practice for Oral Health Care: Future Transformative Effects.

KNOWLEDGE TRANSFER STATEMENT: The results of this study can help key stakeholders, such as health care facilities, educational and research institutions, insurance companies, and governmental bodies, plan future activities and policies on dental practice and education.

Regional mu opioid receptor regulation of sensory and affective dimensions of pain.

The endogenous opioid system is involved in stress responses, in the regulation of the experience of pain, and in the action of analgesic opiate drugs. We examined the function of the opioid system and mu-opioid receptors in the brains of healthy human subjects undergoing sustained pain. Sustained pain induced the regional release of endogenous opioids interacting with mu-opioid receptors in a number of cortical and subcortical brain regions. The activation of the mu-opioid receptor system was associated with reductions in the sensory and affective ratings of the pain experience, with distinct neuroanatomical involvements. These data demonstrate the central role of the mu-opioid receptors and their endogenous ligands in the regulation of sensory and affective components of the pain experience.

Servo-controlled stepped and ramped mechanical tissue algometry.

A hand-held, servo-controlled tissue palpation device (SCPD) was developed to measure the pressure-pain characteristics of human tissue for disease states linked to altered pressure-pain sensitivity. The design was based on an adaptive controller using force feedback to reach and maintain a desired force in spite of movements of the operator's hand holding the device or positional changes of the subject.

Spatial and temporal summation of sensory and affective dimensions of deep somatic pain.

There is considerable evidence in support of differential information processing of the sensory-discriminative and motivational-affective meanings of pain. The purpose of this work was to examine whether temporal (acute, tonic, persistent) and spatial (local, regional, widespread) aspects of deep somatic pain influence the sensory and affective dimensions of pain. Acute pain consisted of a short bout of pain, lasting about 100 s. Tonic pain was the experience of experimentally maintained pain for 18 min. Both acute and tonic pain were induced by infusion of an algesic or control substance into muscle with the subject blinded with respect to the type of infusion and randomization of the application sequence. Comparing the response of experimental subjects to a group of matched cases with persistent masticatory myalgia alone or in combination with widespread musculoskeletal pain, we examine whether the experimental state is different from the matched clinical condition, and whether there is a difference between the condition being restricted to the face or not. The McGill pain questionnaire was used to assess the sensory and affective correlates of pain. The normalized sensory score for acute/unilateral face pain was different from that established for tonic/unilateral face pain (P = 0.055, borderline s.), and so was the normalized affective score (P = 0.009, s.). When comparing tonic/unilateral versus tonic/bilateral face pain, the affective scores increased with increased pain involvement (P = 0.009, s.) while the sensory sores were unaffected by the additional pain induced in the contralateral masseter muscle (P = 0.357, n.s). Notably, sensory and affective scores for tonic/bilateral and persistent/bilateral face pain were not statistically different (sensory: P = 0.169, n.s.; affective: P = 0.643, n.s). On the other hand, when contrasting persistent/bilateral face pain with persistent/ widespread musculoskeletal pain, both scores were significantly different (sensory: P < 0.001, s.; affective: P = 0.041, s.). Time in and spread of pain influenced the perceptual correlates of pain to a significant degree. The major increase in the sensory dimension occurred from 'no pain' to 'acute pain'. Affective scores showed the most significant increases from acute to tonic pain, particularly with greater spatial involvement. The significant increases in sensory scores observed when contrasting persistent facial pain alone and in combination with widespread musculoskeletal pain was attributed to the broader body experience. Because the perceptual correlates of tonic and matched persistent (chronic) pain states were similar, we concluded that it does not require months for the development of the sensory and affective meaning of persistent pain as assumed.

Habituation of the early pain-specific respiratory response in sustained pain.

Neurokinin-1 receptor and mu-opioid receptor agonists affect respiratory rhythm when injected directly into the preBötzinger brainstem complex, which is the hypothesized site for respiratory rhythmogenesis in mammals (Science 286 (1999) 1566). Early stress-induced analgesia (SIA) is naloxone-insensitive and as such considered independent of the activation of the mu-opioid system. Prolonged application of electrical shocks, however, produces analgesia that is mediated by the mu-opioid system (Science 208 (1980) 623). Together these findings suggest that any early pain-specific increased respiration should be attenuated in the tonic state of pain. Ten healthy, pain-free female volunteer subjects participated in this experimental study involving deep acute and tonic pain. The experimental design included three conditions: (1) baseline; (2) pain; and (3) a placebo control stimulus. Experimental pain was induced by the infusion of hypertonic saline into the masseter muscle. Infusion of isotonic saline in the contralateral masseter was used as a control. Blinded subjects were randomly assigned to a particular sequential order of the experimental stages, i.e. hypertonic saline infusion preceded the isotonic saline infusion or vice versa. Respiration rate, mean peak inspiratory and expiratory flow rates, and the minute ventilation volume quantified breathing. Results indicate that effects on respiration were pain-specific and that the early effects on respiration were significantly attenuated in sustained pain. In the early stage of pain, all monitored variables (respiration rate, minute ventilation volume, and inspiratory and expiratory flow rates) were elevated to statistically significant degrees when compared to measurements taken at baseline or during control infusion. Only respiration rate continued to be significantly elevated in sustained pain. We concluded that rhythmogenic neurons in the preBötzinger brainstem complex appear as the likely target for pro-nociceptive and anti-nociceptive input, explaining both the observed initial facilitation and subsequent habituation of respiration in early and sustained pain.

The effect of experimental jaw muscle pain on postural muscle activity.

The purpose of this study was to examine whether tonic muscle pain of an intensity at least as great as that reported by the majority of chronic muscle pain patients causes an increase in postural electromyographic activity of the affected musculature. Twenty young adults volunteered for experiments, knowing that they involved experimental pain. We chose a controlled, two-period crossover and repeated measures design involving four experimental conditions: (1) baseline 1, (2) tonic experimental muscle pain, (3) sham pain, and (4) baseline 2. Subjects were randomly assigned to one of two sequential orders that differed with respect to whether tonic pain preceded sham pain or vice versa. At the within-subject level, the condition (baseline 1, sham pain, tonic pain, baseline 2) had a statistically significant effect on mean rms electromyographic activity at all four recording sites. We found that postural activities at all four recording sites, left/right masseter and left/right anterior temporalis were statistically different from baseline 1 and 2 during tonic pain (P < 0.004, s.; P < 0.024, s.). However, postural activities during tonic pain and sham pain were not significantly different from each other (P < 0.493, n.s.). We concluded that our data do not support the hyperactivity model which assumes a re-enforcing link between pain and muscle hyperactivity.

Greater disability with increased pain involvement, pain intensity and depressive preoccupation.

Persistent pain is often accompanied by functional disability. This study investigated the effect of pain extent and the involvement of specific pain sites on pain-related disability, as determined by the Pain Disability Index (PDI). Complete data were available from 278 persistent facial pain (PFP) patients. Patients were divided into one of two groups based on drawings of their pain distribution. When the patient's pain drawing was limited to the region supplied by the trigeminal nerves (Nn. V(1) V(2), and/or V(3)), with or without the inclusion of any combination of the cervical dermatomes C2, C3 and C4, the patient was assigned to the local/regional pain group. If the pain extended beyond this area, the patient was allocated to the group exhibiting widespread pain. In addition to the PDI, patients filled out the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). The local/regional pain group had significantly lower scores on the PDI, the BDI and STAI state than cases with widespread pain. Patients with widespread pain who indicated pain locations in any one or more of the extremities plus the lower back scored significantly higher on the PDI and the BDI than patients with no such combined involvement. Multiple regression analysis revealed that depressive preoccupation, pain extent and pain intensity were significant predictors of pain-related disability, whereas the STAI was not. If controlled for pain extent and pain intensity, the presence of high as opposed to low depressive scores added almost 11 points to the PDI score. These results showed that pain distribution, pain intensity and depressive mood are significant predictors of pain-related disability.

Textural properties of food used in studies of mastication.

Foods are known to influence jaw elevator muscle activity in chewing. With the long-range goal of gaining insight into force control and modeling muscle recruitment, these initial experiments were performed to determine the textural properties of commonly used test food. Experiments were carried out by means of a standard Instron instrument, equipped with a compression cell. A stylus with 45-degree cuspal angulation and an opposing copper-plated lower arch was used for approximation of the natural situation. The breakage force characteristics of a single peanut, a carrot cube, beefstick, and monkey chow were determined. The peanut demonstrated the steepest and beefstick the least steep force build-up, with breaking forces of 104 N (Newtons) for monkey chow, 66 N for the carrot, and 52 N for the peanut. No clear breakage point was found with beefstick; the force build-up showed an initial plateau at 25 N, which was followed by a significantly steeper force increase to peak. We conclude that each of the test foods commonly used in studies of mastication had particular breakage characteristics in terms of its force-time curve.

Pain maps from facial pain patients indicate a broad pain geography.

Two hundred consecutive female patients, who were referred to a university-based facial pain clinic, were asked to mark all painful sites on sketches showing the contours of a human body in the frontal and rear views. The drawings were analyzed with transparent templates containing 1875 (frontal view) and 1929 (rear view) square cells of equal size. The average patient scored 71.8 cells in the frontal and 99.7 cells in the rear view (corresponding to 3.8% and 5.2% of the maximum possible scores). In individual patient drawings, however, up to 42.7% and 44.9% of all cells were marked. Only 37 cases (18.5%) exhibited pain that was limited to the trigeminal system. An analysis of the pain distribution according to the arrangements of dermatomes revealed three distinct clusters of patients: (1) pain restricted to the region innervated by the trigeminal nerves (n = 37); (2) pain in the trigeminal dermatomes and any combination involving the spinal dermatomes C2, C3, and C4, but no other dermatomes (n = 32); and (3) pain sites involving dermatomes in addition to the ones listed above (n = 131). Mean ages in the three clusters were 38.7, 35.5, and 37.5 years, respectively (p = 0.62, n.s.). Widespread pain existed for longer durations (median, 48 months) than conditions involving local and regional pain (median, 24 months) (p = 0.02, s.). Our findings showed that among a great percentage of persistent facial pain patients the pain distribution is more widespread than commonly assumed, and that the persistence of pain in the regional and widespread pain presentations is significantly greater than in cases with pain limited to the trigeminal system.

Three-dimensional unilateral method for the bilateral measurement of condylar movements.

Using a unilateral optoelectronic tracking system (JAWS-3D), a method was developed for the simultaneous measurement of the three-dimensional kinematics of both ipsilateral and contralateral human condyles, the latter being represented by virtual points beyond the field of vision of the camera system during the actual recording. The method leaves the subject's head unrestrained while measuring the movements of two sets of three light-emitting diodes rigidly attached to the upper and lower teeth. The Tait-Bryan angles method was employed for calculating the jaw rotations in three dimensions. Movements were referenced to both a skeletal and a dental coordinate system. The worst-case static measurement errors were 0.24 mm for a 20 mm translation and 0.71 degrees for a 35 degrees rotation. The mean dynamic measurement errors were 9.73 microns s-1 at a constant linear velocity of 200 microns s-1 and 0.73 degrees s-1 at a constant angular velocity of 149 degrees s-1. The utility of the method was demonstrated in a subject who was asked to open and close the mouth in a cyclic fashion.

A closed-loop system for maintaining constant experimental muscle pain in man.

Reliable experimental models are needed to help improve our knowledge of how the central nervous system adapts to function in the presence of muscle pain in man. We developed a microprocessor-based control system for maintaining a constant level of experimental muscle pain. Pain was induced in the relaxed right masseter of healthy young adults by using an infusion pump to inject an algesic 0.15 mL bolus of 5% hypertonic saline over 15 s. Subjects supplied feedback on their present pain intensity (PPI) via a 10 cm long electronic visual-analog scale (VAS) and a 0.07 Hz zero-order hold. The adaptive controller identified the system dynamic response and proportional-integral-derivative (PID) controller parameters from the subject's initial response to the bolus (pain rise and fall time constants and peak amplitude) as well as his/her response to a 90 s constant infusion. Finally, using the pain feedback the adaptive PID controller was successfully used to adjust the infusion rate to maintain PPI in five out of seven healthy adults at a mean (SD) 4.8(0.9) PPI level with respect to the 5.0 PPI setpoint for periods up to 15 min (when the experiment was arbitrarily terminated). The infusion rate required to maintain the given level of masseter pain was found to increase by approximately 3 to 5%/minute.

Cervical muscle myoelectric response to acute experimental sternocleidomastoid pain.

A method is presented for investigating the response of passive and active muscle to experimentally induced deep muscle pain. Ten healthy adult males performed multiple, submaximal isometric neck flexion tasks before and after pain had been induced in the sternocleidomastoid (SCM) muscle by injecting 5 ml of a hypertonic (5%) saline solution. A similar volume of isotonic saline was injected into the contralateral muscle as a control. Cervical myoelectric signal (MES) root-mean-square (RMS) response to each injection was recorded from eight neck muscles over 8 minutes. The subject rated perceived pain at regular intervals using a visual analog scale (VAS). Sternocleidomastoid pain, which reached a mean of 36 mm on the 100-mm VAS 2 minutes after the injection, resulted in significantly increased (1-2 microV, P less than 0.05) RMS MES in the otherwise relaxed SCM muscle during the first 2 minutes. This was followed by a gradual return to control values after 5 minutes. A similar trend in MES was found for the active SCM muscle during a 10% maximum voluntary contraction (MVC) isometric neck flexion effort. Thus, acute deep muscle pain caused subtle, yet systematic, changes in motor output in both the relaxed and active painful muscle, and its synergists and antagonists.

A comparative electromyographic and kinesiographic study of deliberate and habitual mastication in man.

Twelve healthy, fully-dentate subjects participated in experiments which included the continuous recording of surface electromyography and jaw movement during habitual and deliberate right-sided or left-sided chewing of a coherent bolus. Analogue data streams were converted to digital values. Root-mean-square (r.m.s.) muscle-activity traces were computed from raw electromyographic data. The working side was defined as the side from which the mandible approached the position of occlusal stoppage when in the most cranially directed part of the chewing cycle. In any given muscle, greater mean peak r.m.s. activities were found with ipsilateral than contralateral bolus replacement (p less than 0.01, s); such differences were more pronounced for the masseter than the anterior temporal muscles. During habitual chewing, mean peak r.m.s. activities exceeded the value established by deliberate mastication with ipsilateral bolus placement in 27 of 48 muscles; this may be because of more vigorous chewing during habitual performance. No subject was strictly unilateral in their preference for bolus placement and in 6 of the 12 subjects, there was a timed side-switching of the bolus within the masticatory sequence. The results also indicated that any averaging of data based upon time-amplitude alone would be inappropriate for habitual chewing because of the call for different working sides within a particular masticatory sequence. Thus a new data format based upon numerical representation of the electromyographic activity against time was introduced.

Predicting foodstuff from jaw dynamics during masticatory crushing in man.

In previous in vitro experiments using an Instron instrument, each test food was found to have characteristic textural properties. In vivo experiments were now made (1) to determine the degree to which variations in the vertical jaw movements during the crushing phase of mastication can be explained by the inherent properties of the foodstuff being chewed, and (2) to establish the degree to which the foodstuff being chewed can be identified by certain features of the jaw dynamics. Five adults were used for chewing tasks with standardized pieces of beef, carrot or peanut. Each subject made two trials with each foodstuff. The movement of the lower incisal point was monitored; features of movement associated with jaw closing in the first chewing cycle were considered. Five of these features were not suitable to categorize the various test foods. Each of the remaining 4, however, was able to distinguish either one food from the 2 others (2 cases), or one from another (2 cases). Pattern recognition techniques based upon principal component analysis could differentiate jaw closing patterns associated with chewing beef from those involving peanut or carrot. The extent to which peanut could be distinguished from carrot was not as predictable as the categorization of peanut or carrot versus beef. Cross-correlation of in vitro force-time breakage characteristics and the jaw movement data showed that on average 52% of the variation in the vertical jaw movement during crushing of food could be explained by the inherent properties of the food.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-linear amplification of electromyographic signals with particular application to human chewing.

A method is described for logarithmically-amplifying electromyographic signals so that the most commonly-occurring events within them are enhanced selectively before digital conversion. There is a need to resolve low and intermediate levels of activity during chewing, while preserving the occasional high-level responses. Besides achieving a higher resolution in subsequent digital sampling, this signal-processing technique increased the representation of low and intermediate activities in polygraphic displays. It further ensured that signals were presented to the A/D converter within the code width of the instrument.

The effects of pain from the mandibular joint and muscles on masticatory motor behaviour in man.

Habitual chewing of a coherent bolus was studied in 12 dentate subjects with painful mandibular-joint disorders and 12 healthy, dentate controls. Bilateral electromyograms of jaw elevators, and jaw movement, were recorded for three complete masticatory sequences. Computer analysis was used to classify chewing movements as continuous or discontinuous. Root-mean-square (r.m.s.), myoelectric signal amplitudes were computed for each of four jaw elevators. Although discontinuous chewing cycles were significantly more frequent in painful function (p = 0.001), they also occurred in pain-free function, a finding which reduces their diagnostic significance. During painless and painful function, r.m.s. activities did not differ statistically when elevators acted as agonists on both the dominant and non-dominant chewing side (p greater than 0.1). When used as antagonists, such as during jaw opening, the elevators had greater mean peak activities during painful than painless function (p = 0.0001). Variability in maximum gape was greater during painful than painless function (p = 0.001), but peak maximum gapes in complete masticatory sequences were not affected by pain, and neither were minimum interocclusal gapes. More frequent reshaping and repositioning of the bolus in the presence of pain could explain these differences between painful and pain-free function.

Short and long latency jaw-opening reflex responses elicited by mechanical stimulation in man.

Jaw-opening reflex responses elicited by tapping the chin during maximum clenching in incisal edge-to-edge contact position were studied in 10 healthy subjects. Stimuli were also delivered during weak clenching on a rubber stamp, separating the incisors by approx. 10 mm and protruding the mandible to the edge-to-edge incisor relationship. All four central incisors were stimulated simultaneously. With weak stimuli, there was a short-latency (9.5 ms) digastric response which may have had a disynaptic pathway. Taps of moderate strength produced long-latency (20 ms) responses, and sometimes a short-latency (9.5 ms) component as well. Strong (non-painful) taps produced an even longer-latency digastric response, 30 ms or more following the stimulus with less synchronization than earlier responses. Jaw-jerk reflexes occurred 8.5 ms following the tap, independently of the magnitude of the stimulus. Local anaesthesia of the upper and lower incisors abolished the digastric muscle response. Thus large periodontal afferents may be responsible for the early digastric reflex activity and smaller fibres for later effects. Temporal summation of the reflex response probably occurred when all incisors were stimulated simultaneously.

Generic pain intensity scores are affected by painful comorbidity.

AIMS: To determine the degree to which the generic pain intensity rating (i.e., overall and without reference to a particular body site) of facial pain patients being seen in a specialty setting for facial pain is influenced by painful comorbidity in body parts other than the face. METHODS: In this prospective study, 40 consecutive female temporomandibular pain patients rated their generic pain on a 100-mm visual analog scale. After marking all painful body sites on pain drawings, patients were asked to rate the pain intensity for each of the indicated pain sites; the patients did not have access to the generic pain intensity score. Pearson's correlation coefficient was used to correlate the generic pain intensity score with site-specific pain intensity ratings, their mean and maximum, and the number of pain sites. RESULTS: The medians of the generic, maximum, and facial pain intensity scores were 49.5, 53, and 45.5, respectively. The generic pain intensity rating correlated more highly with the intensity scores reported for the most painful body site (r2 = 0.82; P < 0.001) than with the average rating across all painful sites (r2 = 0.62; P < 0.001), or the pain intensity score in the face (r2 = 0.61; P < 0.001). The number of pain sites did not correlate to any statistically significant degree with the generic pain intensity rating (r2 = 0.006; P = 0.65). CONCLUSION: The results of this study suggest that the maximum visual analog scale pain intensity score, observed in any body location, is a better reflection of the generic pain intensity rating than the corresponding score of the face. To avoid over-rating or underrating of facial pain intensity, patients should be instructed to provide site-specific pain intensity scores if painful comorbidity is present.