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Biomedical subjects

Roland Staud

Publications and source records attributed to Roland Staud.

At least 19 recordsLinked to original sources
PubMed2006

Brain activity related to temporal summation of C-fiber evoked pain.

Temporal summation of "second pain" (TSSP) is considered to be the result of C-fiber-evoked responses of dorsal horn neurons, termed 'windup'. This phenomenon is dependent on stimulus frequency (0.33 Hz) and relevant for central sensitization and chronic pain. Previous brain imaging studies have only been used to characterize neural correlates of second pain but not its temporal summation. We utilized functional magnetic resonance imaging (fMRI) in healthy volunteers to measure brain responses associated with TSSP. Region of interest analysis was used to assess TSSP related brain activation. Eleven pain-free normal subjects underwent fMRI scanning during repetitive heat pulses to the right foot at 0.33 and 0.17 Hz. Stimulus intensities were adjusted to each individual's heat sensitivity to achieve comparable TSSP ratings of moderate pain in all subjects. As predicted, experimental pain ratings showed robust TSSP during 0.33 Hz but not 0.17 Hz stimuli. fMRI statistical maps identified several brain regions with stimulus and frequency dependent activation consistent with TSSP, including contralateral thalamus (THAL), S1, bilateral S2, anterior and posterior insula (INS), mid-anterior cingulate cortex (ACC), and supplemental motor areas (SMA). TSSP ratings were significantly correlated with brain activation in somatosensory areas (THAL, S1, left S2), anterior INS, and ACC. These results show that neural responses related to TSSP are evoked in somatosensory processing areas (THAL, S2), as well as in multiple areas that serve other functions related to pain, such as cognition (ACC, PFC), affect (INS, ACC, PAG), pre-motor activity (SMA, cerebellum), and pain modulation (rostral ACC).

Anxiety↗
PubMed2006

Biology and therapy of fibromyalgia: pain in fibromyalgia syndrome.

Fibromyalgia (FM) pain is frequent in the general population but its pathogenesis is only poorly understood. Many recent studies have emphasized the role of central nervous system pain processing abnormalities in FM, including central sensitization and inadequate pain inhibition. However, increasing evidence points towards peripheral tissues as relevant contributors of painful impulse input that might either initiate or maintain central sensitization, or both. It is well known that persistent or intense nociception can lead to neuroplastic changes in the spinal cord and brain, resulting in central sensitization and pain. This mechanism represents a hallmark of FM and many other chronic pain syndromes, including irritable bowel syndrome, temporomandibular disorder, migraine, and low back pain. Importantly, after central sensitization has been established only minimal nociceptive input is required for the maintenance of the chronic pain state. Additional factors, including pain related negative affect and poor sleep have been shown to significantly contribute to clinical FM pain. Better understanding of these mechanisms and their relationship to central sensitization and clinical pain will provide new approaches for the prevention and treatment of FM and other chronic pain syndromes.

Fibromyalgia↗
PubMed2006

Are patients with systemic lupus erythematosus at increased risk for fibromyalgia?

Widespread chronic pain, fatigue, and distress do not represent risk factors for future systemic lupus erythematosus (SLE) or other autoimmune syndromes. On the other hand, SLE seems to be a significant risk factor for fibromyalgia (FM). Up to 47% of SLE patients fulfill FM criteria. SLE patients with concomitant FM are often highly symptomatic and dysfunctional. The presence of FM symptoms in SLE patients, however, does not predict more extensive organ involvement or lupus activity. The high concordance of SLE with FM suggests common mechanisms related to pain and distress in both patient groups. Recent research suggests involvement of N-methyl-D-aspartate (NMDA) and neurokinin receptor systems. Thus, autoimmune activity against these receptor systems in SLE patients could result in pain, cognitive defects, and chronic pain states including FM. Conversely, treatment of SLE-FM patients with inhibitors of NMDA or neurokinin receptors may prevent or alleviate cognitive abnormalities and chronic pain, as well as FM.

Comorbidity↗
PubMed2006

Advanced continuous-contact heat pulse design for efficient temporal summation of second pain (windup).

UNLABELLED: Temporal summation of second pain or windup (WU(SP)) can be reliably evoked in normal human subjects by repetitive heat pulses to the skin at frequencies of 0.33 Hz or more. This phenomenon is dependent on activation of peripheral C-nociceptors and central N-methyl-D-aspartate receptors, resulting in windup of C-fiber-evoked discharges of dorsal horn neurons. Several investigations of heat pain summation have used Peltier devices for intermittent-contact heat pulses to the skin. This method returns the skin to an adapting temperature between each stimulus and can result in distinct first and second pain sensations. An alternative method of temporal summation consists of continuous-contact heat stimuli by computerized Peltier thermodes that can provide rapid heat pulses. Previously used continuous-contact heat pulse trains, however, seemed to lack characteristics that result in efficient WU(SP). The present study sought to obtain psychophysical evidence that reliable WU(SP) can be elicited with an advanced pulse design by using a computerized heat-foil/Peltier thermode. WU(SP) was elicited by repetitive thermal stimulation of the hands at frequencies of 0.33 Hz but not 0.25 and 0.17 Hz. WU(SP) stimuli were either adjusted to resemble the heat transfer characteristics of intermittent-contact stimulus trains, or they remained unadjusted. The estimated transmission velocity of impulses giving rise to second pain and WU(SP) was characteristic of C fibers. More pronounced second pain and efficient WU(SP) could be elicited with adjusted than with unadjusted heat pulse trains. Thus, specifically designed continuous-contact heat pulses can be used to elicit distinct second pain and robust WU(SP), thereby providing an efficient psychophysical test of this phenomenon. PERSPECTIVE: Temporal summation testing is rapidly becoming a relevant psychophysical tool for the study of chronic pain disorders. The results of this study will allow more efficient use of currently available constant-contact thermodes for clinical and research applications.

Adult↗
PubMed2006

Mechanisms of disease: pain in fibromyalgia syndrome.

Despite extensive research, the pathogenesis of pain in fibromyalgia syndrome is incompletely understood. Fibromyalgia pain is consistently felt in deep tissues including ligaments, joints and muscles. Increasing evidence points towards these tissues as relevant contributors of nociceptive input that might either initiate or maintain central sensitization, or both. Persistent or intense nociception can lead to transcriptional and translational changes in the spinal cord and brain resulting in central sensitization and pain. This mechanism represents a hallmark of fibromyalgia and many other chronic pain syndromes, including irritable bowel syndrome, temporomandibular disorder, migraine, and low back pain. Importantly, after central sensitization has been established, only minimal nociceptive input is required for the maintenance of the chronic pain state. Other factors, including pain-related negative affect, have been shown to significantly contribute to clinical fibromyalgia pain. An improved understanding of the mechanisms that characterize central sensitization and clinical pain will provide new approaches for the prevention and treatment of fibromyalgia and other chronic pain syndromes.

Autonomic Nervous System↗
PubMed2006

Mechanisms of acupuncture analgesia for clinical and experimental pain.

There is convincing evidence that acupuncture (AP) is effective for the treatment of postoperative and chemotherapy-induced nausea/vomiting, as well as postoperative dental pain. Less convincing data support AP's efficacy for chronic pain conditions, including headache, fibromyalgia and low back pain. There is no evidence that AP is effective in treating addiction, insomnia, obesity, asthma or stroke deficits. AP seems to be efficacious for alleviating experimental pain by increasing pain thresholds in human subjects and it appears to activate analgesic brain mechanisms through the release of neurohumoral factors, some of which can be inhibited by the opioid antagonist naloxone. In contrast to placebo analgesia, AP-related pain relief takes some time to develop and to resolve. Furthermore, repetitive use of AP analgesia can result in tolerance that demonstrates cross-tolerance with morphine. However, it appears that not all forms of AP are equally effective for providing analgesia. In particular, electro-AP seems to best deliver stimuli that activate powerful opioid and nonopioid analgesic mechanisms. Thus, future carefully controlled clinical trials using adequate electro-AP may be able to provide the necessary evidence for relevant analgesia in chronic pain conditions, such as headache, fibromyalgia, irritable bowel syndrome and low back pain.

Acupuncture Analgesia↗
PubMed2006

Are tender point injections beneficial: the role of tonic nociception in fibromyalgia.

Characteristic symptoms of fibromyalgia syndrome (FM) include widespread pain, fatigue, sleep abnormalities, and distress. FM patients show psychophysical evidence for mechanical, thermal, and electrical hyperalgesia. To fulfill FM criteria, the mechanical hyperalgesia needs to be widespread and present in at least 11 out of 18 well-defined body areas (tender points). Peripheral and central abnormalities of nociception have been described in FM and these changes may be relevant for the increased pain experienced by these patients. Important nociceptor systems in the skin and muscle seem to undergo profound changes in FM patients by yet unknown mechanisms. These changes may result from the release of algesic substances after muscle or other soft tissue injury. These pain mediators can sensitize important nociceptor systems, including the transient receptor potential channel, vanilloid subfamily member 1 (TRPV1), acid sensing ion channel (ASIC) receptors, and purino-receptors (P2X3). Subsequently, tissue mediators of inflammation and nerve growth factors can excite these receptors and cause substantial changes in pain sensitivity. FM pain is widespread and does not seem to be restricted to tender points (TP). It frequently comprises multiple areas of deep tissue pain (trigger points) with adjacent much larger areas of referred pain. Analgesia of areas of extensive nociceptive input has been found to provide often long lasting local as well as general pain relief. Thus interventions aimed at reducing local FM pain seem to be effective but need to focus less on tender points but more on trigger points (TrP) and other body areas of heightened pain and inflammation.

Botulinum Toxins↗
PubMed2005

Isometric exercise has opposite effects on central pain mechanisms in fibromyalgia patients compared to normal controls.

Aerobic exercise has been shown to activate endogenous opioid and adrenergic systems and attenuate experimental pain in normal control subjects (NC). In contrast, fibromyalgia (FM) subjects' experimental pain ratings increase after aerobic exercise, suggestive of abnormal pain modulation. In order to determine whether central or peripheral mechanisms are predominantly involved in the abnormal pain modulation of FM patients, the effects of handgrip exercise on thermal (cutaneous) and mechanical (somatic) experimental pain was tested in local as well as remote body areas of FM and NC subjects. Supra-threshold thermal pain ratings and pressure pain thresholds over both forearms were obtained before and during 90 s of sustained 30% maximal voluntary contraction (MVC). This isometric exercise resulted in substantially decreased thermal pain ratings and increased mechanical thresholds in local as well as remote body areas in NC. Opposite effects were detected in FM patients. Thus, sustained local muscular contraction induced widespread pain inhibitory effects in NC. In contrast, the widespread hyperalgesic effects of exercise on FM patients clearly indicate altered central pain mechanisms. However, whether these exercise effects of FM patients result from abnormal descending inhibition or excessive activation of muscle nociceptive afferents needs to be addressed in future studies.

Exercise↗
PubMed2005

Predictors of clinical pain intensity in patients with fibromyalgia syndrome.

Central changes in pain processing have been previously reported in patients with fibromyalgia syndrome. These changes include decreased thresholds to mechanical and thermal stimuli (allodynia) and central sensitization, both of which are fundamental to the generation of clinical pain. Therefore, psychophysical measures of central pain processing may be useful predictors of clinical pain intensity of fibromyalgia syndrome patients. Previous studies of fibromyalgia syndrome patients have shown statistically significant correlations of psychophysical test results with clinical pain intensity. The tests used to characterize this important relationship were dependent on spinal cord pain mechanisms and included temporal summation of pain or wind-up and wind-up after-sensations. Particularly, the magnitude of wind-up after-sensations appeared to be one of the best predictors for clinical pain intensity of fibromyalgia syndrome patients (27%). Furthermore, the combination of tender point count, negative affect, and wind-up after-sensations accounted for approximately 50% of the variance in clinical pain intensity of fibromyalgia syndrome patients. Therefore, wind-up after-sensations, tender point count, and negative affect not only seem to represent relevant pain mechanisms but also strongly emphasize their importance for fibromyalgia syndrome pain.

Fibromyalgia↗
PubMed2005

Vitamin D: more than just affecting calcium and bone.

Vitamin D is a fat-soluble steroid that is essential for maintaining normal calcium metabolism. In vitamin D deficiency, calcium absorption is insufficient and cannot satisfy the body's needs. Consequently, parathyroid hormone production increases and calcium is mobilized from bones and reabsorbed in the kidneys to maintain normal serum calcium levels--a condition defined as secondary hyperparathyroidism. Most organs, including the gut, brain, heart, pancreas, skin, kidneys, and immune system have receptors for 1,25 (OH)vitamin D. Furthermore, all of these organs have the capacity to synthesize 1,25 (OH)vitamin D from vitamin D. Extensive research suggests that vitamin D deficiency is common and represents a global health problem. Clinical consequences related to low vitamin D levels include not only osteomalacia, osteoporosis, and rickets, but also neuro-muscular dysfunction and fractures. Falls related to neuromuscular dysfunction lead to 40% of all nursing home admissions and are the largest single cause of injury-related deaths in elderly people. About one-third of all persons 65 and older fall at least once a year, resulting in more than 1.5 million emergency room treatments and more than 300,000 hospitalizations. Falls cause more than 11,000 deaths per year, most of them in elderly patients (> or = 75 years) who suffer hip fractures. It is well established that vitamin D deficiency not only has serious consequences for bone health, but also for other organ systems. Previous studies have shown that vitamin D supplementation reduces the number of fractures and directly improves neuromuscular function, thus helping to prevent falls and subsequent fractures. In addition, vitamin D appears to have other important functions as a regulator of cell differentiation and cell growth.

Bone Density Conservation Agents↗
PubMed2005

Morphine responses and experimental pain: sex differences in side effects and cardiovascular responses but not analgesia.

UNLABELLED: Sex differences in analgesic responses to mu opioid agonists have been reported, although the direction of these differences varies across studies. To further characterize sex differences in responses to mu opioids, the analgesic effects of intravenous morphine (0.08 mg/kg) were determined in healthy women (n = 61) and men (n = 39) by using 3 experimental pain models, heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both morphine and saline, which occurred on separate days in counterbalanced order. Although morphine produced significant analgesic effects for all pain stimuli, no significant sex differences in morphine analgesia emerged. However, morphine attenuated cardiovascular reactivity to the ischemic pain task in men but not women, and women reported significantly more drug-related adverse effects than men. These findings are in contrast with some recent clinical and experimental results suggesting more robust analgesic response to mu opioids among women compared to men, although the data indicate that sex differences in non-analgesic effects of morphine were present. These results suggest that sex differences in responses to morphine might depend on the pain model and/or drug dose as well as the specific end point assessed. PERSPECTIVE: This study examines morphine responses in women and men by using laboratory pain measures. The results indicate no sex differences in analgesia, but women reported greater side effects, and morphine attenuated cardiovascular responses more strongly among men than women. These results add to the literature regarding sex differences in response to opioids.

Adult↗
PubMed2005

The A118G single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans.

Responses to painful stimuli are characterized by tremendous interindividual variability, and genetic factors likely account for some proportion of this variability. However, few studies have identified genetic contributions to experimental pain perception in humans. This experiment investigated whether the A118G single nucleotide polymorphism of the mu-opioid receptor gene ( OPRM1 ) was associated with responses to three different experimental pain modalities in a sample of 167 healthy volunteers (96 female, 71 male). Responses to thermal, mechanical, and ischemic pain were assessed in all subjects, and genotyping of OPRM1 was performed, which revealed that the rare A118G allele occurred in 24 females (25%) and 12 males (17%). Statistical analyses indicated that subjects with a rare allele had significantly higher pressure pain thresholds than those homozygous for the common allele. Also, a sex by genotype interaction emerged for heat pain ratings at 49 degrees C, such that the rare allele was associated with lower pain ratings among men but higher pain ratings among women. These data indicate an association of a common single nucleotide polymorphism of OPRM1 with mechanical pain responses and that this genotype may be associated with heat pain perception in a sex-dependent manner. This study examines the association of the A118G SNP of OPRM1 to experimental pain sensitivity. The results indicate that the rare allele is associated with higher pressure pain thresholds. These results support previous contentions that OPRM1 may be a pain-relevant gene; however, replication of these findings is needed.

Adult↗
PubMed2005

Effects of the N-methyl-D-aspartate receptor antagonist dextromethorphan on temporal summation of pain are similar in fibromyalgia patients and normal control subjects.

UNLABELLED: Temporal summation of second pain at least partly reflects temporal summation of dorsal horn neuronal responses, and both have been termed windup (WU), a form of nociception-dependent central sensitization. Animal and human experiments have shown that both forms of WU depend on N-methyl-D-aspartate (NMDA) and substance P receptor systems. WU of second pain (WU(SP)) in patients with fibromyalgia (FM) is enhanced compared with normal control (NC) subjects and is followed by exaggerated WU(SP) aftersensations and prolonged WU(SP) maintenance at low stimulus frequencies. Because the enhanced WU(SP) of FM patients could be related to abnormal endogenous modulation of NDMA receptors, we tested the effects of the NMDA receptor antagonist dextromethorphan (DEX) on WU(SP) in FM and NC subjects in a double-blind, placebo-controlled, crossover study. WU(SP) was elicited by trains of 0.7-second duration thermal pulses applied to the glabrous surface of the hands or by 1-second mechanical stimuli to the adductor pollicis muscle of the hands at a frequency of 0.33 Hz. In comparison to baseline and placebo conditions, single oral doses of DEX 60 and 90 mg reduced thermal and mechanical WU(SP) in NC and FM subjects, with DEX 90 mg being most effective. These effects did not differ for male and female NC subjects. FM subjects required less thermal and mechanical stimulus intensity than NC to achieve maximal WU(SP), but the extent of WU(SP) reduction by DEX did not statistically differ between NC and FM subjects for all study conditions. Thus, central pain processing of FM subjects is not different from NC in at least one important aspect, namely their NMDA receptor system responsiveness to pharmacologic inhibition by DEX. PERSPECTIVE: Results of this study demonstrate that FM patients show abnormal WU(SP) during thermal and mechanical stimulation compared with NC. Because oral doses of the NMDA receptor antagonist DEX attenuated thermal and mechanical WU(SP) similarly in FM patients and NC, other mechanisms than WU(SP) need to be considered for the widespread pain of FM patients. These mechanisms might include tonic nociceptive input from peripheral tissues and/or enhanced descending facilitation.

Adult↗
PubMed2005

Cluster analysis of multiple experimental pain modalities.

Identifying individual differences in pain is an important topic; however, little is known regarding patterns of responses across various experimental pain modalities. This study evaluated subgroups emerging from multiple experimental pain measures. One hundred and eighty-eight individuals (59.0% female) completed several psychological instruments and underwent ischemic, pressure, and thermal pain assessments. Thirteen separate pain measures were obtained by using three experimental pain modalities with several parameters tested within each modality. The pain ratings and scores were submitted to factor analysis that identified four pain factors from which Pain Sensitivity Index (PSI) scores were computed: heat pain (HP), pressure pain (PP), ischemic pain (IP), and temporal summation of heat pain (TS). Cluster analyses of PSI scores revealed four distinct clusters. The first cluster demonstrated high overall pain sensitivity, the second cluster revealed high TS, the third cluster showed particular insensitivity to IP and low sensitivity across pain modalities except PP, and the fourth cluster demonstrated low sensitivity to PP. Significant correlations were found between psychological measures and Index scores and those differed by sex. Cluster membership was associated with demographic variables of ethnicity and sex as well as specific psychosocial variables, although cluster differences were only partially explained by such factors. These analyses revealed that groups respond differently across varied pain stimuli, and this was not related solely to demographic or psychosocial factors. These findings highlight the need for future investigation to identify patterns of responses across different pain modalities in order to more accurately characterize individual differences in responses to experimental pain.

Adolescent↗
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

Sex-related psychological predictors of baseline pain perception and analgesic responses to pentazocine.

Sex differences in pain perception and analgesic responses have garnered increasing attention in recent years. We examined the association of psychological factors to baseline pain perception and pentazocine analgesia among 49 healthy women and 39 men. Subjects completed psychological questionnaires measuring positive and negative affect as well as catastrophizing. Subsequently, responses to experimental pain were assessed before and after double-blind administration of intravenous pentazocine (0.5mg/kg). In correlational analyses, positive affect predicted lower pain sensitivity among men but not women. Negative affect predicted lower baseline pain tolerances among both sexes but predicted poorer analgesia only among men. Catastrophizing was associated with greater pain sensitivity and less analgesia more consistently in men than women. Regression models revealed that positive affect predicted lower overall pain sensitivity and catastrophizing predicted poorer overall analgesic responses among men, while no significant predictors of overall pain or analgesia emerged for women. Moreover, positive affect and catastrophizing were negatively and positively correlated, respectively, with side effects from the medication, but only among men. These findings indicate sex-dependent associations of psychological factors with baseline pain perception, analgesic responses, and medication side effects.

Adult↗