Differential psychophysiological effects of operant and cognitive behavioural treatments in women with fibromyalgia.

BACKGROUND: Determination of psychophysiological effects of operant behavioural (OBT) and cognitive behavioural treatment (CBT) for fibromyalgia patients. METHODS: One hundred and fifteen female patients randomized to OBT (N = 43), CBT (N = 42), or whole-body infrared heat (IH) (N = 30) were compared before and after group treatment as well as at 6- and 12-month follow-ups using intent-to-treat analysis (12 drop-outs). Thirty matched pain-free controls (CON) served as reference group for the initial psychophysiological analysis. Surface electromyogram (EMG), blood pressure, heart rate (HR) and skin conductance levels (SCL) were continuously recorded during adaptation, baseline, social conflict, mental arithmetic and relaxation tasks. RESULTS: At baseline, fibromyalgia patients showed higher SCL and HR, lower diastolic blood pressure and EMG in comparison to controls. OBT and CBT compared to IH significantly reduced pain intensity [OBT: effect size (ES) = 1.21 CI: 0.71-1.71, CBT: ES = 1.23, CI: 0.72-1.74]. OBT increased diastolic blood pressure [ES = 1.13, CI: 0.63-1.63 and CBT reduced SCL (ES) = -0.66, CI: -1.14-0.18] 12 months after treatment. Both CBT and OBT significantly increased EMG levels (OBT: ES = 0.97, CI: 0.48-1.46, CBT: ES = 1.17, CI: 0.67-1.68). In contrast, the IH group did not show any significant changes in the psychophysiological parameters. CONCLUSION: Increased diastolic blood pressure and decreased pain after OBT suggest a reactivation of baroreflex-mechanisms in fibromyalgia and a normalization of the blood pressure and pain functional relationship. Reduced SCL following CBT may indicate reduced general arousal levels. Increased muscle tension after CBT and OBT suggest a normalization of physical parameters. The reduction in pain seems to be mediated by different psychophysiological processes, providing support for mechanism-based treatments might be indicated for CBT and OBT. WHAT DOES THIS STUDY ADD?: Differential physiological stress responses followed different psychological interventions. While OBT influenced blood pressure by restoring blood pressure-pain interaction, CBT reduced stress-related sudomotor activity. These results implicate specific mediating mechanisms in fibromyalgia suggesting a basis for matching based on specific patient psychophysiological features.

Neurosensory assessments of migraine.

Headache medicine is primarily dependent on patients' subjective reports of pain, which are assessed at diagnosis and throughout the duration of treatment. There is a need for an objective, quantitative biological measurement of headache pain severity. In this study, quantitative sensory testing (QST) was conducted via multi-site vibrotactile stimulation in patients with migraine. The purpose was to investigate the sensitivity of the method and to determine if the metrics obtained from migraineurs could be differentiated from controls. Metrics reflecting sensory percepts of baseline measures of stimulus amplitude discrimination, temporal order judgment, and duration discrimination were significantly different. Additional measures previously demonstrated to be sensitive to alterations in centrally-mediated information processing features such as adaptation and synchronization were also significantly different from control values. In contrast, reaction times and vibrotactile detection thresholds of migraineurs failed to differentiate them from controls, indicating that the results are not due to peripheral neuropathy or some other primary afferent mechanism. The long-term objective of the study is to develop methods that can improve diagnosis and enable more accurate assessments of treatment efficacy in migraine.

Using fMRI to evaluate the effects of milnacipran on central pain processing in patients with fibromyalgia.

Background In recent years, the prescription of serotonin-noradrenalin reuptake inhibitors (SNRIs) for treatment of fibromyalgia (FM) has increased with reports of their efficacy. The SNRI milnacipran is approved by the U.S. Food and Drug Administration (FDA) for treatment of FM, yet, the mechanisms by which milnacipran reduces FM symptoms are unknown. A large number of neuroimaging studies have demonstrated altered brain function in patients with FM but the effect of milnacipran on central pain processing has not been investigated. The primary objective of this study was to assess the effect of milnacipran on sensitivity to pressure-evoked pain in FM. Secondary objectives were to assess the effect of milnacipran on cerebral processing of pressure-evoked pain using fMRI and the tolerability and safety of milnacipran 200 mg/day in FM. Methods 92 patients were randomized to either 13-weeks milnacipran treatment (200 mg/day) or placebo in this double-blind, placebo-controlled multicenter clinical trial. Psychophysical measures and functional MRI (fMRI) assessments were performed before and after treatment using a computer-controlled pressure-pain stimulator. Here, we present the results of several a priori defined statistical analyses. Results Milnacipran-treated patients displayed a trend toward lower pressure-pain sensitivity after treatment, compared to placebo, and the difference was greater at higher pain intensities. A single group fMRI analysis of milnacipran-treated patients indicated increased pain-evoked brain activity in the caudatus nucleus, anterior insula and amygdala after treatment, compared to before treatment; regions implicated in pain inhibitory processes. A 2 × 2 repeated measures fMRI analysis, comparing milnacipran and placebo, before and after treatment, showed that milnacipran-treated patients had greater pain-evoked activity in the precuneus/posterior cingulate cortex after treatment; a region previously implicated in intrinsic brain function and FM pathology. This finding was only significant when uncorrected for multiple comparisons. The safety analysis revealed that patients from both treatment groups had treatment-emergent adverse events where nausea was the most common complaint, reported by 43.5% of placebo patients and 71.7% of milnacipran-treated patients. Patients on milnacipran were more likely to discontinue treatment because of side effects. Conclusions Our results provide preliminary indications of increased pain inhibitory responses in milnacipran-treated FM patients, compared to placebo. The psychophysical assessments did not reach statistical significance but reveal a trend toward higher pressure-pain tolerance after treatment with milnacipran, compared to placebo, especially for higher pain intensities. Our fMRI analyses point toward increased activation of the precuneus/posterior cingulum in patients treated with milnacipran, however results were not corrected for multiple comparisons. The precuneus/posterior cingulum is a key region of the default mode network and has previously been associated with abnormal function in FM. Future studies may further explore activity within the default mode network as a potential biomarker for abnormal central pain processing. Implications The present study provides novel insights for future studies where functional neuroimaging may be used to elucidate the central mechanisms of common pharmacological treatments for chronic pain. Furthermore, our results point toward a potential mechanism for pain normalization in response to milnacipran, involving regions of the default mode network although this finding needs to be replicated in future studies.

Fibromyalgia dyscognition: concepts and issues.

Fibromyalgia is characterized by widespread pain and tenderness; however, comorbid cognitive difficulties are a common complaint among patients. Known as fibro fog or dyscognition, this symptom comprises difficulties with complex cognitive processes including memory, executive function, concentration and attention. While the mechanisms that initiate and maintain these cognitive deficits are still largely unknown, recent research has increased the understanding of subjective symptoms and objectively-determined deficits in cognitive performance. Treatments have also improved to include complementary cognitive and physical strategies. This review focuses on issues of dyscognition in fibromyalgia. Details of objective testing methods are not within the scope of this paper.

Posterior insular molecular changes in myofascial pain.

Temporomandibular disorders (TMD) include craniocervical pain conditions with unclear etiologies. Central changes are suspected; however, few neuroimaging studies of TMD exist. Single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) was used before and after pressure-pain testing to assess glutamate (Glu), glutamine (Gln), N-acetylaspartate (NAA), and choline (Cho) levels in the right and left posterior insulae of 11 individuals with myofascial TMD and 11 matched control individuals. Glu levels were significantly lower in all individuals after pain testing. Among those with TMD, left-insular Gln levels were related to reported pain, left posterior insular NAA and Cho levels were significantly higher at baseline than in control individuals, and NAA levels were significantly correlated with pain-symptom duration, suggesting adaptive changes. The results suggest that significant central cellular and molecular changes can occur in individuals with TMD.

Fibromyalgia syndrome: preventive, social and economic aspects.

There many open questions concerning the concept of primary prevention in FM. Diagnostic or classification criteria are not universally accepted, and this leads to difficulties in establishing the onset and duration of the disease. In the case of FM, primary prevention may consist of the immediate care of acute pain or treatment for affective disturbances as we do not have any specific laboratory or instrumental tests to determine risk factors of the disease. The goal of secondary prevention is early detection of the disease when patients are largely asymptomatic and intervention improves outcome. Screening allows for identification of an unrecognized disease or risk factor, which, for potential FM patients, includes analysis of tender points, Fibromyalgia Impact Questionnaire (FIQ), pain location and intensity, and fatigue and sleep complaints. Tertiary prevention inhibits further deterioration or reduces complications after the disease has developed. In FM the aim of treatment is to decrease pain and increase function via multimodal therapeutic strategies, which, in most cases, includes pharmacological and non-pharmacological interventions. Patients with FM are high consumers of health care services, and FM is associated with significant productivity-related costs. The degree of disability and the number of comorbidities are strongly associated with costs. An earlier diagnosis of FM can reduce referral costs and investigations, thus, leading to a net savings for the health care sector. However, every social assessment is closely related to the socio-economic level of the general population and to the legislation of the country in which the FM patient resides.

Fibromyalgia syndrome: definition and diagnostic aspects.

Ever since it was first defined, fibromyalgia (FM) has been considered one of the most controversial diagnoses in the field of rheumatology, to the point that not everybody accepts its existence as an independent entity. The sensitivity and specificity of the proposed diagnostic criteria are still debated by various specialists (not only rheumatologists), whose main criticism of the 1990 American College of Rheumatology criteria is that they identify subsets of particular patients that do not reflect everyday clinical reality. Furthermore, the symptoms characterising FM overlap with those of many other conditions classified in a different manner. Over the last few years, this has led to FM being considered less as a clinical entity and more as a possible manifestation of alterations in the psychoneuroendocrine system (the spectrum of affective disorders) or the stress reaction system (dysfunctional symptoms). More recently, doubts have been raised about even these classifications; and it now seems more appropriate to include FM among the central sensitisation syndromes, which identify the main pathogenetic mechanism as the cause of skeletal and extra-skeletal symptoms of FM and other previously defined "dysfunctional" syndromes.

Etiopathogenetic mechanisms of fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is a common chronic condition of widespread pain with causal mechanisms that are largely unknown. It is characterized by moderate to severe musculoskeletal pain and allodynia, but its pathogenesis appears confined to the nociceptive structures of the central nervous system. FMS is often triggered by negative environmental influences, especially if they occur in childhood. In a fetus, these environmental triggers may influence the development of the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal axis (HPA). Increasing evidence supports the comorbidity of psychological conditions including depression, panic disorders, anxiety, and post-traumatic stress disorder (PTSD). Recent evidence suggests that genetic factors may play a role in the pathogenesis of FMS. Central sensitization has long been associated with FMS pain. It describes enhanced excitability of dorsal horn neurons, which leads to transmission of altered nociceptive information to the brain. Understanding of pathogenetic pathways in FMS has advanced beyond observing patient responses to neurophysiologically targeted therapies and basic research.

Non pharmacological treatments in fibromyalgia.

Fibromyalgia is a complex syndrome associated with significant impairment in quality of life and function and with substantial financial costs. Once the diagnosis is made, providers should aim to increase patients' function and minimize pain. Fibromyalgia patients frequently use alternative therapies, strongly indicating both their dissatisfaction with and the substantial ineffectiveness of traditional medical therapy, especially pharmacological treatments. At present, pharmacological treatments for fibromyalgia have a rather discouraging cost/benefit ratio in terms of poor symptom control and high incidence of side effects. The interdisciplinary treatment programs have been shown to improve subjective pain with greater success than monotherapy. Physical therapies, rehabilitation and alternative therapies are generally perceived to be more "natural," to have fewer adverse effects, and in some way, to be more effective. In this review, physical exercise and multimodal cognitive behavioural therapy are presented as the more accepted and beneficial forms of nonpharmacological therapy.

Symptoms and signs in fibromyalgia syndrome.

Fibromyalgia syndrome (FM) is a common chronic pain condition that affects at least 2% of the adult population. Chronic widespread pain is the defining feature of FM, but patients may also exhibit a range of other symptoms, including sleep disturbance, fatigue, irritable bowel syndrome, headaches, and mood disorders. The etiology of FM is not completely understood and the syndrome is influenced by factors such as stress, medical illness, and a variety of pain conditions. Establishing diagnosis may be difficult because of the multifaceted nature of the syndrome and overlap with other chronically painful conditions. A unifying hypothesis is that FM results from sensitization of the central nervous system; this new concept could justify the variety of characteristics of the syndrome. FM symptoms can be musculoskeletal, non-musculoskeletal, or a combination of both; and many patients will also experience a host of associated symptoms or conditions. The ACR classification criteria focus only on pain and disregard other important symptoms; but three key features, pain, fatigue and sleep disturbance, are present in virtually every patient with FM. Several other associated syndromes, including circulatory, nervous, digestive, urinary and reproductive systems are probably a part of the so called central sensitivity or sensitization syndrome. A minority subgroup of patients (30-40%) has a significant psychological disturbance. Psychological factors are an important determinant of any type of pain, and psychological comorbidity is frequent in FM. Psychiatric disorders most commonly described are mood disorders, but psychiatric illness is not a necessary factor in the etiopathogenesis of FM.

Fibromyalgia syndrome: the pharmacological treatment options.

Pharmacological treatment has been gradually enriched by a variety of compounds; however, no single drug is capable of fully managing the constellation of fibromyalgia (FM) symptoms. Currently, it is not possible to draw definite conclusions concerning the best pharmacological approach to managing FM because results of randomized clinical trials present methodological limitations and therapeutic programs are too heterogeneous for adequate comparison. However, a variety of pharmacological treatments including antidepressants, nonsteroidal anti-inflammatory drugs (NSAIDS), opioids, sedatives, muscle relaxants and antiepileptics have been used to treat FM with varying results. In this review, we will evaluate those pharmacological therapies that have produced the most significant clinical results in treating FM patients. The nature of FM suggests that an individualized, multimodal approach that includes both pharmacologic and nonpharmacologic therapies seems to be the most appropriate treatment strategy to date.

The evaluation of the fibromyalgia patients.

Fibromyalgia (FM) is a rheumatic disease characterized by musculoskeletal pain, chronic diffuse tension and/or stiffness in joints and muscles, easy fatigue, sleep and emotional disturbances, and pressure pain sensitivity in at least 11 of 18 tender points. At present, there are no instrumental tests or specific diagnostic markers for FM; in fact, many of the existing indicators are significant for research purposes only. Many differential diagnoses may be excluded by an extensive clinical examination and patient history. Considering overlap of FM with other medical conditions, the treating physicians should be vigilant: chest-X-rays and abdominal ultrasonography are the first steps of general evaluation for all the patients with suspected FM. Functional neuroimaging methods have revealed a large number of supraspinal effects in FM, a disorder mediated by mechanisms that are essentially unknown. Many treatments are used in FM patients, but evaluating their therapeutic effects in FM is difficult because the syndrome is so multifaceted. To address the identification of core outcome domains, the Initiative on IMMPACT and OMERACT workshop convened a meeting to develop consensus recommendations for chronic pain clinical trials.

[Central pain processing in chronic low back pain. Evidence for reduced pain inhibition]. / Zentrale Schmerzverarbeitung bei chronischem Rückenschmerz. Hinweise auf verminderte Schmerzinhibition.

INTRODUCTION: A study of patients with low back pain (LBP) had revealed altered central pain processing. At an equal pain level LBP patients had considerably more neuronal activation in the somatosensory cortices than controls. In a new analysis of this dataset, we further investigated the differences in central pain processing between LBP patients and controls, looking for possible pathogenic mechanisms. METHODS: Central pain processing was studied by functional magnetic resonance imaging (fMRI), using equally painful pressure stimuli in a block paradigm. In this study, we reanalyzed the fMRI data to statistically compare pain-elicited neuronal activation of both groups. RESULTS: Equally painful pressure stimulation resulted in a significantly lower increase of regional cerebral blood flow (rCBF) in the periaqueductal gray (PAG) of the LBP patients. The analysis further revealed a significantly higher increase of rCBF in LBP than in HC in the primary and secondary somatosensory cortex and the lateral orbitofrontal cortex (LOFK), elicited by these same stimuli. CONCLUSIONS: These findings support a dysfunction of the inhibitory systems controlled by the PAG as a possible pathogenic mechanism in chronic low back pain.

Psychophysical elements of place and modality specificity in the thalamic somatic sensory nucleus (ventral caudal, vc) of awake humans.

Discrete anatomic structures in the monkey somatic sensory thalamus may segregate input arising from different peripheral receptors and from different parts of the body. It has been proposed that these structures serve as components of modality- and place-specific pathways from the periphery to the cortex. We now test this hypothesis by examining the modality- and place-specific segregation of sensations at sites where microstimulation (microA currents) within the region of ventral caudal (Vc; human principal somatic sensory nucleus) evokes somatic sensations. Microstimulation was delivered in an ascending staircase protocol consisting of different numbers of pulses (4-100) presented at different frequencies (10-200 Hz) during awake thalamic surgery for movement disorders. The results demonstrate that the part of the body where microstimulation evoked sensation (projected field) and the descriptors of nonpainful sensations were usually uniform across the staircase. These results strongly support the existence of psychophysical elements of place and modality specificity in the Vc thalamus. The proportion of sites at which the sensation included more than one part of the body almost always stayed constant over current intervals (plateaus) of 10 microA. Similar plateaus were not found for sites with more than one descriptor, suggesting that elements of modality-specificity are smaller than and located within those for place-specificity. The intensity of sensations varied with the number of stimulation pulses for mechanical/tingle and cool sensations. The results provide strong evidence for psychophysically defined elements that are responsible for modality specificity of nonpainful sensations, place specificity, and intensity coding of somatic sensation in the human thalamus.

Pain catastrophizing and neural responses to pain among persons with fibromyalgia.

Pain catastrophizing, or characterizations of pain as awful, horrible and unbearable, is increasingly being recognized as an important factor in the experience of pain. The purpose of this investigation was to examine the association between catastrophizing, as measured by the Coping Strategies Questionnaire Catastrophizing Subscale, and brain responses to blunt pressure assessed by functional MRI among 29 subjects with fibromyalgia. Since catastrophizing has been suggested to augment pain perception through enhanced attention to painful stimuli, and heightened emotional responses to pain, we hypothesized that catastrophizing would be positively associated with activation in structures believed to be involved in these aspects of pain processing. As catastrophizing is also strongly associated with depression, the influence of depressive symptomatology was statistically removed. Residual scores of catastrophizing controlling for depressive symptomatology were significantly associated with increased activity in the ipsilateral claustrum (r = 0.51, P < 0.05), cerebellum (r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.47, P < 0.05), and parietal cortex (r = 0.41, P < 0.05), and in the contralateral dorsal anterior cingulate gyrus (ACC; r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.41, P < 0.05), medial frontal cortex (r = 0.40, P < 0.05) and lentiform nuclei (r = 0.40, P < 0.05). Analysis of subjects classified as high or low catastrophizers, based on a median split of residual catastrophizing scores, showed that both groups displayed significant increases in ipsilateral secondary somatosensory cortex (SII), although the magnitude of activation was twice as large among high catastrophizers. Both groups also had significant activations in contralateral insula, SII, primary somatosensory cortex (SI), inferior parietal lobule and thalamus. High catastrophizers displayed unique activation in the contralateral anterior ACC, and the contralateral and ipsilateral lentiform. Both groups also displayed significant ipsilateral activation in SI, anterior and posterior cerebellum, posterior cingulate gyrus, and superior and inferior frontal gyrus. These findings suggest that pain catastrophizing, independent of the influence of depression, is significantly associated with increased activity in brain areas related to anticipation of pain (medial frontal cortex, cerebellum), attention to pain (dorsal ACC, dorsolateral prefrontal cortex), emotional aspects of pain (claustrum, closely connected to amygdala) and motor control. These results support the hypothesis that catastrophizing influences pain perception through altering attention and anticipation, and heightening emotional responses to pain. Activation associated with catastrophizing in motor areas of the brain may reflect expressive responses to pain that are associated with greater pain catastrophizing.

Sex-dependent components of the analgesia produced by athletic competition.

Competing in various athletic events (track meet, basketball game, or fencing match) can produce analgesia to cold pressor stimuli in male and female college athletes compared with baseline assessments. This competition-induced analgesia has been attributed to the stress associated with competition, which has components related to both physical exercise and the cognitive aspects of competing. This study evaluated the analgesic effect of exercise-related stress, and that caused by the cognitively stressful components of competing independent of exercise. Cold pressor pain ratings were assessed after competition in a track meet and after treadmill exercise or sedentary video game competition in both athletes and nonathletes. As expected, competing in athletics resulted in a decrease in cold pressor ratings in both male and female athletes. Independent of athletic status, treadmill running induced analgesia in women, but not in males, whereas sedentary video game competition produced analgesia in men, but not in women. These findings suggest that different components of the competitive athletic experience might be responsible for the analgesic effects in a sex-dependent manner.

Diagnosing sensory abnormalities with either normal values or values from contralateral skin: comparison of two approaches in complex regional pain syndrome I.

BACKGROUND: To diagnose sensory abnormalities, patient values can be compared with values of the general population (absolute approach) or to values measured at contralateral homologous skin (relative approach). The current study gives normal values for both approaches and compares the advantages of each method by applying the technique to patients with complex regional pain syndrome type I (CRPS I). METHODS: In 50 healthy control subjects, sensory and pain thresholds were measured for pressure, warmth, and cold on both wrists and both feet. In 53 patients with unilateral CRPS I (33 hand, 20 foot), the same assessments were conducted twice, at an interval of 1 month. RESULTS: In control subjects, contralateral homologous sides have approximately the same sensitivity, supporting the validity of the relative approach in patients. Hypoesthesia and allodynia can be diagnosed by either the absolute or relative approach, whereas hyperesthesia and hypoalgesia can only be identified with the relative approach. The two approaches obtain different results in 20% of cases. Age, gender, and subject criteria may influence the absolute but not the relative approach. Both approaches are comparable with regard to reproducibility. Frequency distributions of sensory abnormalities in chronic CRPS I are presented. The most frequent diagnoses were cold allodynia and mechanical hypoesthesia and allodynia. CONCLUSIONS: To divide sensory characteristics into a binary classification of "normal" and "abnormal," the relative approach is the best choice, with the exception of cases in which the contralateral homologous side is absent or affected by disease. The authors recommend the relative approach for both research and clinical purposes.

Pain measurement.

Increasing evidence from laboratory methods in humans and animals indicates that pain arises from, and is modulated by, a number of mechanisms. In addition, these mechanisms are not static but change as pain persists. Recent human studies have demonstrated new aspects of pain processing at all levels of the central nervous system. Studies of the influence of analgesic agents on a large number of experimental pain measures have shown a preferential effect of opioids for attenuating the central integration of prolonged stimuli while local anesthetics may be more effective for brief stimulation. Studies of NK1 antagonists in man have shown results similar to those found with animals. There is little effect on brief stimulation of A delta and C-fiber nociceptors, including conditions that can evoke central summation. However, these antagonists, which block the effects of substance P, are effective in more persistent states such as postsurgical pain. Persistent pain can also alter the function of the large diameter A beta touch afferents, ranging from increased tactile sensitivity in inflammatory conditions to frank allodynia following nerve injury or focal nociceptor stimulation. Recent advances in evaluation of supraspinal pain processing in humans have demonstrated pain-related activation using both methods that assess synchronized neural activity and methods that infer this activity in the whole brain by local changes in regional cerebral blood flow. These methods have begun to identify brain regions associated with the multiple dimensions and processing of painful stimulation and the modulation of these processes by pharmacological agents and non-pharmacological interventions.

Tourniquet constriction exacerbates hyperalgesia-related pain induced by intradermal capsaicin injection.

BACKGROUND: When capsaicin is injected intradermally, hyperalgesia develops around the injection site. The authors observed that volunteers report painful sensations in the skin remote from the injection site during tourniquet constriction of the affected extremity. METHODS: Each volunteer received an intradermal injection of capsaicin on the volar forearm, followed by intermittent tourniquet constriction of the extremity. In some participants, the tourniquet position was rotated between different sites on the upper extremities. Laser Doppler measurements were made in the skin to measure capillary blood flow during pain magnification. RESULTS: Hyperalgesia developed in the volunteers who were tested after the capsaicin injection. Blood flow increased three times in the dermal capillaries remote from the injection site after capsaicin injection. The tourniquet-induced pain reached peak intensity soon after tourniquet inflation. Tourniquet constriction of the arm on the affected side reliably induced painful exacerbation in each person tested. The quality of the sensation was described as burning and extended across the arm in most volunteers. Only when pinprick hyperalgesia was detectable did the volunteers experience the diffuse, immediate pain sensation. The pain initiated by the tourniquet constriction likely is related to changes in skin capillary blood flow. CONCLUSIONS: Low cutaneous blood perfusion is related to the intensity of ongoing, spontaneous pain when secondary hyperalgesia is present. The specific trigger(s) have yet to be identified.