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Biomedical subjects

Donald D Price

Publications and source records attributed to Donald D Price.

At least 37 records · Page 2Linked to original sources
PubMed2005

The effect of propofol on thermal pain perception.

We studied the effect of propofol, a widely used sedative-hypnotic drug, on pain perception. Eighteen subjects received propofol in two sedative concentrations that were balanced and randomized in order. Painful (45 degrees C, 47 degrees C, and 49 degrees C) stimulation temperatures were presented in random order, and nonpainful 31 degrees C stimuli were presented on alternate trials. We used a target-controlled infusion and chose effect site concentrations of 0.5 mug/mL for mild sedation and 1.0 mug/mL for moderate sedation. Using a visual analog scale, subjects rated both pain intensity and unpleasantness higher when sedated with propofol. The average pain intensity was 28/100 for placebo, 35/100 for mild, and 40/100 for moderate sedation. Pain unpleasantness was 23/100 for placebo, 29/100 for mild, and 33/100 for moderate sedation. This effect was unexpected and may be explained by a difference of subjective pain experience by a patient and the perceived level of analgesia by a health care provider in sedated patients. This finding calls further attention to the need for adequate analgesia in patients sedated with propofol.

Adult↗
PubMed2005

Neurobiology of fibromyalgia syndrome.

Accumulating evidence suggests that fibromyalgia syndrome (FM) pain is maintained by tonic impulse input from deep tissues, such as muscle and joints, in combination with central sensitization mechanisms. This nociceptive input may originate in peripheral tissues (trauma and infection) resulting in hyperalgesia/allodynia and/or central sensitization. Evidence for abnormal sensitization mechanisms in FM includes enhanced temporal summation of delayed pain in response to repeated heat taps and repeated muscle taps, as well as prolonged and enhanced painful after-sensations in FM patients but not control subjects. Moreover, magnitudes of enhanced after-sensations are predictive of FM patients' ongoing clinical pain. Such alterations of relevant pain mechanisms may lead to longterm neuroplastic changes that exceed the antinociceptive capabilities of affected individuals, resulting in ever-increasing pain sensitivity and dysfunction. Future research needs to address the important role of abnormal nociception and/or antinociception for chronic pain in FM.

Acute Disease↗
PubMed2004

Representations of pain in the brain.

In this paper, the relationships between neural mechanisms of persistent pain and the neural representations of these conditions in the human and animal brain will be reviewed. Animal models of chronic pain, such as the sciatic nerve constrictive injuries, are accompanied by somatotopically organized increases in several pain-related areas of the brain. Recent human brain imaging studies utilizing functional magnetic resonance imaging and positron emission tomography have elucidated the cerebral representations of visceral and somatic hypersensitivity. Both forms of hypersensitivity are represented in similar brain regions that are activated during acute pain, yet have a more extensive or intense cerebral representation. This suggests that these somatic and visceral hyperalgesic states may be represented by increased activity in the same cerebral pathways and centers that are involved in nociceptive stimuli in normal individuals. Hyperalgesic states during clinically relevant pain are especially reflected in brain areas such as the anterior cingulate and prefrontal cortical regions.

Afferent Pathways↗
PubMed2004

Influences of gender role and anxiety on sex differences in temporal summation of pain.

UNLABELLED: Previous research has consistently shown moderate to large differences between pain reports of men and women undergoing experimental pain testing. These differences have been shown for a variety of types of stimulation. However, only recently have sex differences been demonstrated for temporal summation of second pain. This study examined sex differences in response to temporal summation of second pain elicited by thermal stimulation of the skin. The relative influences of state anxiety and gender role expectations on temporal summation were investigated. Asymptomatic undergraduates (37 women and 30 men) underwent thermal testing of the thenar surface of the hand in a temporal summation protocol. Our results replicated those of Fillingim et al indicating that women showed increased temporal summation compared to men. We extended those findings to demonstrate that temporal summation is influenced by anxiety and gender role stereotypes about pain responding. When anxiety and gender role stereotypes are taken into account, sex is no longer a significant predictor of temporal summation. These findings highlight the contribution of social learning factors in the differences between sexes' pain perception. PERSPECTIVE: Results of this study demonstrate that psychosocial variables influence pain mechanisms. Temporal summation was related to gender role expectations of pain and anxiety. These variables explain a significant portion of the differences between men and women's pain processing, and may be related to differences in clinical presentation.

Adolescent↗
PubMed2004

Body pain area and pain-related negative affect predict clinical pain intensity in patients with fibromyalgia.

UNLABELLED: Patients with fibromyalgia (FM) report widespread chronic musculoskeletal pain. Palpation of 9 paired tender points (TPs) is commonly used for the diagnosis of FM according to criteria specified by the American College of Rheumatology. Although TP palpation can be used to assess deep tissue hypersensitivity, it has failed as a reliable indicator of clinical pain intensity in FM. The sum of local areas of pain (SLAP) obtained from a body pain diagram represents a relevant measure of the spatial extent of clinical pain, a feature most likely important for FM pain. Because spatial summation of pain can be an important determinant of clinical pain intensity, we hypothesized that this measure would predict clinical pain intensity in FM patients. Because pain is strongly associated with negative emotions, we evaluated the relationship of pain-related negative affect (PRNA) with clinical pain intensity in FM. The independent contributions of SLAP, PRNA, and TP count to the variance of clinical pain intensity were assessed in 280 FM patients. Clinical pain intensity of 280 FM patients was measured by using a visual analogue scale. FM patients shaded all painful body areas on body pain diagrams. Dolorimetry was used for TP evaluations. PRNA was assessed with the Medical College of Virginia Pain Questionnaire. Hierarchical linear regression was used to test the association of SLAP, TPs, and PRNA with clinical pain intensity. FM patients' mean visual analogue scale rating (0 to 100) of usual clinical pain was 50.1. Mean SLAP, TP count, and PRNA were 11.4, 16.0, and 44.3, respectively. Hierarchical linear regression analysis identified SLAP, TP count, and PRNA as independent predictors of clinical pain that accounted for 45% of the variance in clinical pain intensity ratings in FM patients. Consistent with the literature, TP count predicted only a small part (4%) of this variance. Our statistical model of body pain areas and negative affect predicts a large portion of the variance of pain intensity in FM. This result suggests that the extent of pain areas and negative emotions are uniquely associated with clinical pain intensity in FM. PERSPECTIVE: The number of painful body areas obtained by body pain diagrams is a better predictor of clinical pain intensity than TPs in FM patients. The combination of painful body areas, TP counts, and PRNA predicts 45% of the clinical pain intensity of FM patients. This finding might be useful for clinical evaluations of FM patients.

Adult↗
PubMed2004

Maintenance of windup of second pain requires less frequent stimulation in fibromyalgia patients compared to normal controls.

Many chronic pain syndromes, including fibromyalgia (FM), show evidence of central nervous system hyperexcitability related to central sensitization. Windup (WU) of second pain reflects increased excitability of spinal cord neurons that is related to central sensitization. Psychophysical testing can help characterize this important central nervous system phenomenon because of the parallels between electrophysiological WU and WU of second pain. Animal experiments have shown that once WU has been established, only low frequency tonic nociceptive input is required to maintain the sensitized state of dorsal horn neurons (WU-maintenance or WU-M). The stimulus frequency necessary to maintain the hyperexcitability of spinal cord neurons can provide a measure of central sensitization. Because central sensitization plays an important role in many chronic pain syndromes including FM, we compared WU-M in 72 normal controls (NC) and 104 FM subjects. WU of second pain was produced by a train of 0.7 s duration thermal pulses applied to the glabrous surface of the hands at a frequency of 0.3 Hz. Enhanced second pain associated with WU could, thereafter, be maintained in FM but not NC subjects for up to 120 s by stimuli delivered at 0.16 and 0.08 Hz (WU-M stimuli). These two frequencies of stimulation do not produce WU when delivered alone. Thus, unlike NC subjects, FM subjects showed enhanced second pain during WU-M stimuli at very low stimulus frequencies, indicating central sensitization. Increased WU sensitivity, enhanced WU-M, and increased WU-related aftersensations help account for persistent pain conditions in FM subjects. In addition to WU, WU-M appears to be a useful tool to study mechanisms of pain in patients with characteristics of central sensitization.

Adult↗
PubMed2004

Spatial summation of heat pain within and across dermatomes in fibromyalgia patients and pain-free subjects.

The mechanisms of spatial summation of pain (SSP) include pain coding dependent on impulse frequency and the number of recruited central neurons. However, SSP may also be influenced by pain inhibitory mechanisms, such as diffuse noxious inhibitory controls. Abnormal interactions between pain inhibitory mechanisms and SSP may be relevant for chronic pain conditions such as fibromyalgia (FM) and may help explain why widespread pain is characteristic for this chronic pain syndrome. The present study was designed to determine the difference of thermal SSP in the upper extremities between FM and normal control (NC) subjects, particularly within and across dermatomes of the hand. Fourteen NC and 19 FM subjects were enrolled in this study. SSP testing sessions involved immersion of each individual fingertip as well as stepwise immersion of the fingers, hands, and forearms in a hot water bath (46 degrees Celsius) for 5s and 20s. In addition, immersion of several fingertips across dermatome C(7)-C(8) was compared to progressive immersion of the index finger (dermatome C(7)). These experiments demonstrated significant spatial summation of heat-induced pain in both FM and NC subjects. SSP was most extensive within the fingers, and became negligible as the stimulus area increased above the hand. Furthermore, SSP was more pronounced within one dermatome such as that of the index finger than across several dermatomes of the hand. These results were similar for both FM and NC subjects. Thus, mechanisms of SSP, including possible inhibitory factors that limit this relevant pain mechanism, appear to be similar for both FM and NC subjects.

Adult↗
PubMed2004

Experimental pain models reveal no sex differences in pentazocine analgesia in humans.

BACKGROUND: Accumulating evidence suggests that there are sex differences in analgesic responses to opioid agonists. Several studies using an oral surgery pain model have reported more robust analgesia to kappa-agonist-antagonists (e.g., pentazocine, nalbuphine, butorphanol) among women than among men. However, evidence of sex differences in kappa-agonist-antagonist effects from studies of experimentally induced pain in humans is lacking. METHODS: Therefore, the analgesic effects of intravenous pentazocine (0.5 mg/kg) were determined in healthy women (n = 41) and men (n = 38) using three experimental pain models: heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both pentazocine and saline, which occurred on separate days in counterbalanced order. RESULTS: Compared with saline, pentazocine produced significant analgesic responses for all pain stimuli. However, no sex differences in pentazocine analgesia emerged. Effect sizes for the sex differences were computed; the magnitude of effects was small, and an equal number of measures showed greater analgesia in men than in women. Also, analgesic responses were not highly correlated across pain modalities, suggesting that different mechanisms may underlie analgesia for disparate types of pain. CONCLUSIONS: These findings indicate significant analgesic responses to pentazocine in both men and women across multiple experimental pain assays, and the absence of sex differences contrasts with previous data from the oral surgery model. The most likely explanation for the discrepancy in results is that of differences in the pain assays. These findings are important because they suggest that sex differences in opioid analgesia may be specific to certain types of pain.

Adolescent↗
PubMed2003

Diffuse noxious inhibitory controls (DNIC) attenuate temporal summation of second pain in normal males but not in normal females or fibromyalgia patients.

Diffuse noxious inhibitory control (DNIC) is part of a central pain modulatory system that relies on spinal and supraspinal mechanisms. Previous studies have shown that fibromyalgia (FMS) patients are lacking DNIC effects on experimental pain, compared to normal control (NC) subjects. Because DNIC has a greater effect on second pain than on first pain, we hypothesized that wind-up (WU) of second pain should be attenuated by a strong conditioning stimulus. Thus, we compared DNIC's effect on WU in three groups of subjects: 11 NC males, 22 NC females, and 11 FMS females. To separately assess the contributions of distraction related mechanisms to inhibition of second pain, we designed the experiment in such a way that directed the subjects' attention to either the test or conditioning stimulus. Repeated heat taps to the thenar surface of the right hand were used as test stimuli to generate WU of second pain. Immersion of the left hand into a hot water bath was the conditioning stimulus. As previous experiments have shown, DNIC requires a strong conditioning stimulus for pain attenuation, which may be at least partly dependent on a distraction effect. DNIC significantly inhibited thermal WU pain in normal male subjects, but adding distraction to the DNIC effect did not increase the extent of this inhibition. In contrast, neither DNIC nor DNIC plus distraction attenuated thermal WU pain in female NCs. DNIC plus distraction but not DNIC alone produced significant inhibition of thermal WU pain in female FMS patients. Our results indicate that DNIC effects on experimental WU of second pain are gender specific, with women generally lacking this pain-inhibitory mechanism.

Adult↗
PubMed2003

Visceral and cutaneous hypersensitivity in Persian Gulf war veterans with chronic gastrointestinal symptoms.

Approximately 697000 United States military personnel participated in the Persian Gulf War (PGW) between August 1990 and March 1991. By April 1997, over 25% of veterans reported chronic health complaints of underdetermined etiology. Gastrointestinal symptoms were among the most frequently reported symptoms including abdominal pain and diarrhea. The objectives of this study were (1). to determine if PGW veterans chronic abdominal pain and diarrhea exhibit visceral and cutaneous hypersensitivity, (2). to determine if these differences in pain sensitivity are significantly associated with psychological stress. A total of 12 veterans (ten males, two females) (39+/-9 years) who were deployed to the Persian Gulf were enrolled. Seven civilians without prior military experience (five males, two females) and five veterans (five males) who had previously been deployed for active combat were enrolled as controls (35+/-9 years). All 12 PGW veterans reported chronic abdominal pain and diarrhea (negative diagnostic workup) that developed during their tour of duty in the Persian Gulf region. All patients completed a battery of psychological assessments and then randomly received experimental visceral (rectal distension of 35 and 55 mmHg for 30s) and cutaneous (immersion of right foot in 45 and 47 degrees C water for 30s) pain stimuli after which they rated their pain intensity and pain unpleasantness on a continuous visual analogue scale (M-VAS) scale. The trials were repeated and the mean M-VAS scores for the two trials were recorded for each subject. In comparison to controls, PGW subjects reported statistically significant higher mean ratings of pain intensity and pain unpleasantness in response to 35 and 55 mmHg rectal distention (P<0.001) and in response to 45 and 47 degrees C water immersion (P<0.001) of the hand and foot. Results of the hierarchical regressions indicated that the psychological measures (i.e. anxiety, somatic focus) accounted for a significant amount of variance in each of the pain measures. PGW veterans who developed chronic abdominal pain and diarrhea during their tour of duty exhibit visceral hypersensitivity similar to patients with the irritable bowel syndrome. These veterans also have cutaneous hypersensitivity and higher levels of anxiety and somatic focus accounting for these differences in pain reporting.

Adult↗
PubMed2003

Temporal summation of pain from mechanical stimulation of muscle tissue in normal controls and subjects with fibromyalgia syndrome.

Individuals diagnosed with fibromyalgia syndrome (FMS) report chronic pain that is frequently worsened by physical activity and improved by rest. Palpation of muscle and tendinous structures suggests that nociceptors in deep tissues are abnormally sensitive in FMS, but methods of controlled mechanical stimulation of muscles are needed to better characterize the sensitivity of deep tissues. Accordingly, force-controlled mechanical stimulation was applied to the flexor digitorum muscle of the forearm in a series of brief contacts (15 stimuli, each of 1s duration, at 3 or 5s interstimulus intervals). Repetitive stimulation was utilized to determine whether temporal summation of deep muscular pain would occur for normal subjects and would be enhanced for FMS subjects. Moderate temporal summation of deep pain was observed for normal controls (NC), and temporal summation was greatly exaggerated for FMS subjects. Temporal summation for FMS subjects occurred at substantially lower forces and at a lower frequency of stimulation. Furthermore, painful after-sensations were greater in amplitude and more prolonged for FMS subjects. These observations complement a previous demonstration that temporal summation of pain and after-sensations elicited by thermal stimulation of the skin are moderately enhanced for FMS subjects. Abnormal input from muscle nociceptors appears to underlie production of central sensitization in FMS that generalizes to input from cutaneous nociceptors.

Adult↗
PubMed2003

Central representation of visceral and cutaneous hypersensitivity in the irritable bowel syndrome.

We have previously shown that irritable bowel syndrome (IBS) patients have both visceral and cutaneous hyperalgesia. The neural mechanisms of these forms of hyperalgesia were further characterized by comparing cortical processing of both rectal distension (35, 55mmHg) and cutaneous heat nociceptive stimuli (foot immersion in 45 and 47 degrees C water bath) in IBS patients and in a group of healthy age/sex-matched controls. Our approach relied on functional magnetic resonance imaging neuroimaging analyses in which brain activation in age/sex-matched control subjects was subtracted from that found in IBS patients. These analyses revealed that both rectal distension and cutaneous heat stimuli evoked greater neural activity in several brain regions of IBS patients in comparison to age/sex-matched control subjects. These include those related to early stages of somatosensory processing (e.g. thalamus, somatosensory cortex) as well as those more related to cognitive and affective processing (insular, anterior cingulate, posterior cingulate, prefrontal cortex). Thus, our results support the hypothesis that hyperalgesia of IBS is manifested by increased somatosensory processing at all cortical levels. This was found to be the case not only for visceral hyperalgesia but also for cutaneous heat hyperalgesia, a likely form of secondary hyperalgesia. Furthermore, visceral and heat hyperalgesia were accompanied by increased neural activity within the same brain structures. These results support the hypothesis that visceral and cutaneous hyperalgesia in IBS patients is related to increased afferent processing in pathways ascending to the brain rather than to selectively increased activity at higher cortical levels (e.g. limbic and frontal cortical areas).

Adult↗
PubMed2003

The contributions of suggestion, desire, and expectation to placebo effects in irritable bowel syndrome patients. An empirical investigation.

In order to investigate external factors that may influence the magnitude of placebo analgesia as well as psychological factors that mediate placebo analgesia, 13 irritable bowl syndrome (IBS) patients rated evoked rectal distension and cutaneous heat pain under the conditions of natural history (NH), rectal placebo (RP), rectal nocebo (RN), rectal lidocaine (RL) and oral lidocaine (OL). Patients were given verbal suggestions for pain relief and rated expected pain levels and desire for pain relief for both evoked visceral and cutaneous pain, respectively. Large reductions in pain intensity and pain unpleasantness ratings were found in the RP, RL and OL condition as compared to the natural history condition, whereas no significant difference in pain reduction between the three treatment conditions was found. Ratings during RN and NH were not statistically different. Compared to a previous study, which shows that rectal lidocaine reverses visceral and cutaneous hyperalgesia, these results suggest that adding a verbal suggestion for pain relief can increase the magnitude of placebo analgesia to that of an active agent. Since IBS patients rate these stimuli as much higher than do normal control subjects and since placebo effects were very large, they probably reflect anti-hyperalgesic mechanisms to a major extent. Expected pain levels and desire for pain relief accounted for large amounts of the variance in visceral pain intensity in the RP, RL, and OL condition (up to 81%), and for lower amounts of the variance in cutaneous pain intensity. Hence, the combination of expected pain levels and desire for pain relief may offer an alternative means of assessing the contribution of placebo factors during analgesia.

Administration, Oral↗
PubMed2003

Ratings of experimental pain and pain-related negative affect predict clinical pain in patients with fibromyalgia syndrome.

Patients with fibromyalgia syndrome (FMS) report chronic pain related to abnormal sensitivity of muscles that is reflected by so-called tender points (TP). TP represent areas of abnormal mechanical pain thresholds that have only shown a minor correlation with clinical pain of FMS patients and seem to be better suited for predicting distress. Pain-related negative affect (PRNA), abnormal temporal summation of second pain (termed wind-up or WU), and abnormal WU decay are frequently present in FMS patients. WU and WU decay can provide measures of central sensitization, which may contribute to clinical FMS pain. We therefore investigated the role of WU, WU decay, TP count, and PRNA as predictors of clinical pain in FMS subjects.Fifty-five FMS subjects rated their clinical pain at entry into the study using a visual analogue scale (VAS). After a TP evaluation, all subjects received two trials of thermal WU and WU decay testing. Hierarchical regression analysis demonstrated that the combination of PRNA ratings, TP count, and WU decay ratings predicted 49.7% of the variance of clinical pain in FMS. This model demonstrates independent relationships of biological and psychological factors to clinical pain and underscores the important role of abnormal peripheral and central pain mechanisms for FMS. Therefore, the combination of PRNA, TP count, and WU decay may provide an excellent measure for future clinical studies of FMS patients.

Adult↗
PubMed2003

Reversal of visceral and cutaneous hyperalgesia by local rectal anesthesia in irritable bowel syndrome (IBS) patients.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal illnesses and is characterized by altered visceral perception. The aim of the study was to determine if local anesthetic blockade of peripheral visceral nociceptive input reduces both visceral and cutaneous secondary hyperalgesia in IBS patients. Ten women with IBS (mean age 30+/-10 years) and ten control subjects (all women) (mean age 29+/-7 years) rated pain intensity and unpleasantness to distension of the rectum (35 mmHg) and thermal stimulation (47 degrees C) of the foot before and after rectal administration of either lidocaine jelly or saline jelly in a double blind crossover design. Intrarectal lidocaine (300 mg) reduced reported rectal and cutaneous pain in all of the IBS patients. The effects were statistically much greater than those of placebo and most of the effects were present within 5-15 min after the onset of the treatment. In the control subjects, rectal lidocaine did not decrease pain report from visceral and cutaneous stimuli. The results of this study support the hypothesis that local anesthetic blockade of peripheral impulse input from the rectum/colon reduces both visceral and cutaneous secondary hyperalgesia in IBS patients. The results provide further evidence that visceral hyperalgesia and secondary cutaneous hyperalgesia in IBS reflects central sensitization mechanisms that are dynamically maintained by tonic impulse input from the rectum/colon. Rectal administration of lidocaine jelly may also be a safe and effective means of reducing pain symptoms in IBS patients.

Administration, Rectal↗
PubMed2003

Altering gender role expectations: effects on pain tolerance, pain threshold, and pain ratings.

The literature demonstrating sex differences in pain is sizable. Most explanations for these differences have focused on biologic mechanisms, and only a few studies have examined social learning. The purpose of this study was to examine the contribution of gender-role stereotypes to sex differences in pain. This study used experimental manipulation of gender-role expectations for men and women. One hundred twenty students participated in the cold pressor task. Before the pain task, participants were given 1 of 3 instructional sets: no expectation, 30-second performance expectation, or a 90-second performance expectation. Pain ratings, threshold, and tolerance were recorded. Significant sex differences in the "no expectation" condition for pain tolerance (t = 2.32, df = 38, P <.05) and post-cold pressor pain ratings (t = 2.6, df = 37, P <.05) were found. Women had briefer tolerance times and higher post-cold pressor ratings than men. When given gender-specific tolerance expectations, men and women did not differ in their pain tolerance, pain threshold, or pain ratings. This is the first empirical study to show that manipulation of expectations alters sex differences in laboratory pain.

Adult↗