F. Petzke

Increased pain sensitivity in fibromyalgia: effects of stimulus type and mode of presentation

&NA; Fibromyalgia (FM) is defined in part by sensitivity to blunt pressure. Pressure pain sensitivity in FM is evaluated typically by the use of ‘ascending’ testing methods such as tender point counts or dolorimetry, which can be influenced by response bias of both the subject and examiner. Methods that present stimuli in a random, unpredictable fashion might minimize the influence of these factors. In this study, we compared the results of ascending and random assessments of both pressure and thermal pain sensitivities in 43 FM patients and 28 age‐ and gender‐matched controls. Even though FM is defined on the basis of pressure sensitivity, this group was also more sensitive to heat stimuli, presented in either ascending or random paradigms. In both the patient and control groups, the pain ratings to painful sensations evoked by both thermal and pressure stimuli were significantly greater in the random, compared with the ascending method. The number of subjects classified as ‘expectant’ because they rated pain higher in ascending than random paradigms was similar for FM and control groups. Both patients and controls exhibited a similar degree of sensitization to pressure and thermal stimuli. The increased sensitivity to both pressure and thermal stimuli for threshold and suprathreshold stimuli in FM patients is consistent with central augmentation of pain processing.

Comparative Efficacy and Harms of Duloxetine, Milnacipran, and Pregabalin in Fibromyalgia Syndrome

UNLABELLED Duloxetine (DLX), milnacipran (MLN), and pregabalin (PGB) are the only drugs licensed by the US Food and Drug Administration (FDA) for fibromyalgia syndrome (FMS). Evidence on the comparative benefits and harms is still accruing. The authors searched MEDLINE, SCOPUS, Cochrane Central Register of Controlled Trials, and sought unpublished data from the databases of FDA, US National Institutes for Health, and Industry through May 2009 for randomized controlled trials. Outcomes of interest were symptom reduction (pain, fatigue, sleep disturbance, depressed mood, reduced health-related quality of life), and adverse events. 17 studies with 7,739 patients met the inclusion criteria. The 3 drugs were superior to placebo except DLX for fatigue, MLN for sleep disturbance, and PGB for depressed mood. Adjusted indirect comparisons indicated no significant differences for 30% pain relief and dropout rates due to adverse events between the 3 drugs. Significant differences in average symptom reduction were found: DLX and PGB were superior to MLN in reduction of pain and sleep disturbances. DLX was superior to MLN and PGB in reducing depressed mood. MLN and PGB were superior to DLX in reducing fatigue. The risk of headache and nausea with DLX and MLN was higher compared with PGB. The risk of diarrhea was higher with DLX compared to MLN and PGB. There is evidence for the short-term (up to 6 months) efficacy of DLX, MLN, and PGB. Differences with regard to the occurrence of the key symptoms of FMS and to drug-specific adverse events may be relevant for the choice of medication. PERSPECTIVE This article presents comparative data on the efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome. The results can help clinicians in choosing medication since the 3 drugs have different effects on the key symptoms of fibromyalgia syndrome and differences in side effects, contraindications, and warnings.

Patients with fibromyalgia display less functional connectivity in the brain's pain inhibitory network

BackgroundThere is evidence for augmented processing of pain and impaired endogenous pain inhibition in Fibromyalgia syndrome (FM). In order to fully understand the mechanisms involved in FM pathology, there is a need for closer investigation of endogenous pain modulation. In the present study, we compared the functional connectivity of the descending pain inhibitory network in age-matched FM patients and healthy controls (HC).We performed functional magnetic resonance imaging (fMRI) in 42 subjects; 14 healthy and 28 age-matched FM patients (2 patients per HC), during randomly presented, subjectively calibrated pressure pain stimuli. A seed-based functional connectivity analysis of brain activity was performed. The seed coordinates were based on the findings from our previous study, comparing the fMRI signal during calibrated pressure pain in FM and HC: the rostral anterior cingulate cortex (rACC) and thalamus.ResultsFM patients required significantly less pressure (kPa) to reach calibrated pain at 50 mm on a 0–100 visual analogue scale (p < .001, two-tailed). During fMRI scanning, the rACC displayed significantly higher connectivity to the amygdala, hippocampus, and brainstem in healthy controls, compared to FM patients. There were no regions where FM patients showed higher rACC connectivity. Thalamus showed significantly higher connectivity to the orbitofrontal cortex in healthy controls but no regions showed higher thalamic connectivity in FM patients.ConclusionPatients with FM displayed less connectivity within the brain’s pain inhibitory network during calibrated pressure pain, compared to healthy controls. The present study provides brain-imaging evidence on how brain regions involved in homeostatic control of pain are less connected in FM patients. It is possible that the dysfunction of the descending pain modulatory network plays an important role in maintenance of FM pain and our results may translate into clinical implications by using the functional connectivity of the pain modulatory network as an objective measure of pain dysregulation.

Overlapping structural and functional brain changes in patients with long-term exposure to fibromyalgia pain

OBJECTIVE There is vast evidence to support the presence of brain aberrations in patients with fibromyalgia (FM), and it is possible that central plasticity is critical for the transition from acute to chronic pain. The aim of the present study was to investigate the relationship between brain structure and function in patients with FM. METHODS Functional connectivity of the brain during application of intermittent pressure-pain stimuli and measures of brain structure were compared between 26 patients with FM and 13 age- and sex-matched healthy controls. Magnetic resonance imaging (MRI) was performed to obtain high-resolution anatomic images and functional MRI scans of the brain, which were used for measurements of pain-evoked brain activity. RESULTS FM patients displayed a distinct overlap between decreased cortical thickness, decreased brain volumes, and decreased functional regional coherence in the rostral anterior cingulate cortex. The morphometric changes were more pronounced with longer exposure to FM pain. In addition, there was evidence of an association between structural and functional changes in the mesolimbic areas of the brain and the severity of comorbid depression symptoms in FM patients. CONCLUSION The combined integration of structural and functional measures allowed for a unique characterization of the impact of FM pain on the brain. These data may lead to the identification of early structural and functional brain alterations in response to pain, which could be used to develop markers for predicting the development of FM and other pain disorders.

Temporal Presentation of Chronic Cancer Pain: Transitory Pains on Admission to a Multidisciplinary Pain Clinic

Transitory flares of pain are well-recognized events in both untreated and treated patients suffering from chronic cancer pain. For the purpose of this survey, we refer to transitory pain (TP) as any event subjectively characterized by transience and pain intensity over a baseline pain. In Part I, TP was reported by 243 (39%) of 613 consecutive cancer pain patients. Gender, age, tumor site, stage, and therapy were not related to the presence of TP. Neuropathic baseline pain was associated with a higher prevalence of TP (P < 0.0001). TP was somatic in 39%, visceral in 22%, and neuropathic in 36% of patients. TP intensity was severe or worse in 92% of patients. Neuropathic TP was briefer and occurred more frequently than nociceptive TP. In Part II, further features of TP were surveyed in 55 patients. Patients reported spontaneous occurrence of TP (40%), a relationship to movement (36%), to the analgesic regimen (35%), to coughing (11%), and to various other factors (18%). Only half of the movement-related TP were predictable. Rescue medication was at least partially effective in 75% of patients. Change in position, rest, diversion, and physiotherapy were commonly employed to alleviate TP. This survey outlined a framework to characterize TP that may prove useful to clarify the definition, pathophysiology, and prevalence of these pains.

Transdermal fentanyl for the management of cancer pain: a survey of 1005 patients.

Transdermal fentanyl was released in Germany in 1995. From October 1996 to February 1998 transdermal treatment was documented for 1005 patients (506 men and 499 women with a mean age of 60 years, range 20–92 years) with chronic pain in an open survey including 290 physicians from hospitals and general practitioners throughout Germany. Most patients suffered from cancer pain and only 11 patients had chronic pain from non-malignant disease. Physicians were asked to complete a questionnaire for patients treated with transdermal fentanyl on initiation of therapy (day 0), and days 3, 6, 18, 30 thereafter, followed by monthly follow-up intervals. Patients were asked to complete a pain diary. Transdermal therapy was documented from day 0 for 824 patients, while 181 patients had been treated with transdermal fentanyl before admission in the survey. Most of the other 824 patients had been treated with other step 3 opioids (55% of the patients) or step 2 opioids (23%) before conversion to transdermal fentanyl, whereas 8% had been treated only with non-opioids and 14% had received analgesics only as required or not at all before initiation of transdermal therapy. The most important reasons for switching to transdermal opioid therapy were insufficient pain relief with the previous medication followed by a variety of gastrointestinal symptoms impeding oral analgesic therapy. Initial fentanyl doses ranged from 0.6 to 9.6 mg/day (25 to 400 [.mu]g/h) with a median of 1.2 mg/day (50 [.mu]g/h). Median doses slowly increased throughout the observation period to 2.4 mg/day (100 [.mu]g/h) after 4 months of treatment. Most patients continued transdermal therapy until the time of death (47% of patients). Other reasons for discontinuation were inadequate pain relief (10%), pain relief with other analgesic regimens (10%), other symptoms than pain (5%), rejection of transdermal therapy by the patient (6%) or miscellaneous (16%). Adverse events were documented as the reason for discontinuation of transdermal therapy in 49 patients (5%). Dyspnoea was documented for seven patients as the reason for discontinuation. One of these patients, as well as another patient with an episode of apnoea, had to be treated with artificial respiration for several hours, but both patients recovered without sequelae. Transdermal therapy with fentanyl was safe and efficient in this national survey. Transdermal fentanyl can be recommended for treatment of moderate to severe cancer pain and probably may even be used as a first-line drug on step 3 of the World Health Organization recommendations in selected patient groups.

Comorbid Somatic Symptoms and Functional Status in Patients With Fibromyalgia and Chronic Fatigue Syndrome: Sensory Amplification as a Common Mechanism

BACKGROUND Somatic symptoms are common in conditions such as fibromyalgia (FM) and chronic fatigue syndrome (CFS). OBJECTIVE Authors investigated a potential shared pathologic mechanism: a generalized perceptual abnormality where there is heightened responsiveness to varied sensory stimulation, including pain. METHOD A composite measure of sensory sensitivity was created and compared with measures of somatic symptoms, comorbid psychological disturbances, and self-reported physical functioning in 38 patients with FM and/or CFS. RESULTS Sensory amplification influenced physical functioning indirectly through pain intensity, and physical symptoms and fatigue also independently contributed to physical functioning. CONCLUSION Sensory amplification may be an underlying pathophysiologic mechanism in these disorders that is relatively independent of depression and depressive symptoms.

Preoperative pain as a risk factor for chronic post-surgical pain - six month follow-up after radical prostatectomy.

Background: Chronic post‐surgical pain (CPSP) by definition develops for the first time after surgery and is not related to any preoperative pain. Preoperative pain is assumed to be a major risk factor for CPSP. Prospective studies to endorse this assumption are missing.

Differences in unpleasantness induced by experimental pressure pain between patients with fibromyalgia and healthy controls

Pain possesses both sensory and affective dimensions, which are highly correlated yet distinct. Comparison of these dimensions within experimental pain settings has resulted in the construct of relative unpleasantness. Relative unpleasantness is defined as the amount of affective unpleasantness elicited for a given sensory magnitude. The aim of this study was to determine the relationship between affective and sensory components of evoked pain in subjects with fibromyalgia (FM) and healthy controls. Here we show that patients with FM unexpectedly display less relative unpleasantness than healthy controls in response to random noxious pressure stimuli. Relative unpleasantness was not correlated with distress, anxiety, or depression, which were pronounced in the FM group. Clinical pain in patients with FM was perceived to be more unpleasant than the evoked pain stimuli. These results are consistent with the concept that chronic pain may reduce the relative unpleasantness of evoked pain sensations.

Anxiety and Depressive Symptoms in Fibromyalgia Are Related to Poor Perception of Health but Not to Pain Sensitivity or Cerebral Processing of Pain

OBJECTIVE Mood disturbance is common among patients with fibromyalgia (FM), but the influence of psychological symptoms on pain processing in this disorder is unknown. We undertook the present study to investigate the differential effect of depressive symptoms, anxiety, and catastrophizing on 1) pain symptoms and subjective ratings of general health status and 2) sensitivity to pain and cerebral processing of pressure pain. METHODS Eighty-three women (mean ± SD age 43.8 ± 8.1 years) who fulfilled the American College of Rheumatology 1990 criteria for the classification of FM participated in the study. Patients rated pain intensity (100-mm visual analog scale [VAS]), severity of FM (Fibromyalgia Impact Questionnaire), general health status (Short Form 36), depressive symptoms (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory), and catastrophizing (Coping Strategies Questionnaire). Experimental pain in the thumb was induced using a computer-controlled pressure stimulator. Event-related functional magnetic resonance imaging was performed during administration of painful stimuli representing 50 mm on a pain VAS, as well as nonpainful pressures. RESULTS A correlation analysis including all self-ratings showed that depressive symptoms, anxiety, and catastrophizing scores were correlated with one another (P < 0.001), but did not correlate with ratings of clinical pain or with sensitivity to pressure pain. However, the subjective rating of general health was correlated with depressive symptoms and anxiety (P < 0.001). Analyses of imaging results using self-rated psychological measures as covariates showed that brain activity during experimental pain was not modulated by depressive symptoms, anxiety, or catastrophizing. CONCLUSION Negative mood in FM patients can lead to a poor perception of ones physical health (and vice versa) but does not influence performance on assessments of clinical and experimental pain. Our data provide evidence that 2 partially segregated mechanisms are involved in the neural processing of experimental pain and negative affect.