We examined the effects of corticotropin-releasing factor (CRF) on plasticity of optically recorded neuronal activity in the substantia gelatinosa (lamina II) of 12-18-day-old rat spinal cord slices stained with a voltage-sensitive dye. Single-pulse test stimulation to the dorsal root that activated A and C fibres evoked prolonged (>100 ms) light-absorption change in the lamina II. This response represents the gross membrane potential change of all elements along the slice depth. After conditioning high-frequency stimulation of A-fibre-activating strength, test stimulus elicited less neuronal activity [-27+/-1% (7), (average+/-SE (n)), P<0.01 (*) at 45-60 min after conditioning]. When CRF (1 microM, 10 min) was applied during conditioning, the neuronal activity was facilitated rather than suppressed [+20+/-3% (5), P<0.05]. CRF alone exhibited insignificant effect [-5+/-1% (4), P=0.2]. In the presence of the inhibitory amino acid antagonists bicuculline (1 microM) and strychnine (0.3 microM) in the perfusate, in contrast, the conditioning facilitated it [+27+/-1% (12)*], and CRF treatment during conditioning inhibited the facilitation dose-dependently [0.1 microM: +18+/-2% (5)*, 1 microM: +13+/-1% (7)*]. Although interneuronal actions might contribute, these results suggest that CRF may have dual effects on excitatory synaptic transmission within the lamina II depending upon cellular conditions: a conversion from the induction of long-term depression to long-term potentiation (LTP), and inhibition of LTP induction. Since the LTP is thought to be responsible at least in part for the persistent pain, CRF could regulate the induction.

Laser evoked potentials (LEPs) are nociceptive-related brain responses to activation of cutaneous nociceptors by laser radiant heat stimuli. We previously showed that LEP amplitude during the P2 period (approximately 400 ms) was increased by rare noxious stimuli, inside and outside the focus of spatial attention. It was postulated that this effect reflected a P3a response indexing an involuntary shift of attention. In the present study, LEPs were recorded in a three-stimulus oddball paradigm, commonly used to evoke P3a (or novelty-P3). CO(2) laser-induced noxious stimuli were delivered on one hand (80%, frequent). Two series of rare stronger-intensity deviant stimuli were randomly intermixed: target stimuli (10%) were delivered on the same hand while distractor stimuli (10%) were delivered on the other hand. Subjects were instructed to count targets. During an additional session, strong stimuli were delivered alone on one hand without instruction (100%, no-task stimuli). All stimulus types evoked a first positivity around 360 ms (P360). Targets and distractors elicited a late positive complex (LPC) around 465-500 ms. Topography of LPC to distractors was central and significantly more anterior than that of LPC to targets. Distractor LPC corresponds to P3a (or novelty-P3) indexing an involuntary orientation of attention toward an unexpected new/deviant event. It suggests that at least an early part of the LEP positivity (P360) is independent of P3-activities.

Injury to peripheral nerves often produces non-physiological, long-lasting spontaneous pain, hyperalgesia and allodynia that are refractory to standard treatment and often insensitive to opioids, such as morphine. Recent studies demonstrate spinal glial activation and increased proinflammatory cytokines in animal models of neuropathic pain. When these data are considered together, a unifying hypothesis emerges which implicates a role of central neuroimmune processes in the etiology of neuronal and behavioral hypersensitivity. The present investigation assessed the influence of propentofylline, a glial modulating and anti-inflammatory agent, on the development of L5 spinal nerve transection-induced hyperalgesia and associated enhancement of spinal neuroimmune responses using real-time reverse transcription-polymerase chain reaction, RNase protection assay, enzyme-linked immunosorbent assay, and immunocytochemistry in rats. The results show that chronic propentofylline treatment attenuated the development of hyperalgesia and restored the analgesic activity of acute morphine in neuropathic rats. These findings directly correlated with the ability of propentofylline to inhibit glial activation and enhanced spinal proinflammatory cytokines following peripheral nerve injury. These findings along with our earlier observations of an anti-allodynic activity of propentofylline using the identical animal model of mononeuropathy supports the concept that modulation of glial and neuroimmune activation may be potential therapeutic targets to treat or prevent neuropathic pain. Further, restoration of the analgesic activity of morphine by propentofylline treatment suggests that increased glial activity and proinflammatory cytokine responses may account for the decreased analgesic efficacy of morphine observed in the treatment of neuropathic pain.

Animal studies have shown that opioids modulate the function of dopaminergic neurons. The effect of alfentanil on cortical and thalamic binding of the D2/D3 receptor ligand [(11)C]FLB 457 was evaluated in eight healthy subjects with positron emission tomography. The simplified reference tissue model was used to calculate tracer binding potential (BP) during a baseline condition and target-controlled infusion of alfentanil, and the results were analyzed using a comparison group not receiving opioid. Behavioral and analgesic effects of alfentanil were also evaluated. In the region-of-interest analysis, alfentanil increased the BP of [(11)C]FLB 457 in the medial frontal cortex (P=0.0027), dorsolateral prefrontal cortex (P=0.027) superior temporal cortex (P=0.028), and medial thalamus (P=0.003) These results were confirmed in a voxel-based analysis, which further revealed an opioid-induced increase in [(11)C]FLB 457 BP in the anterior cingulate cortex (P<0.001). Alfentanil induced euphoria (P=0.003) and analgesia (P=0.006) Cheerfulness (r=0.918, P=0.001) and euphoria (r=0.982, P<0.001) were associated with increased BP of [(11)C]FLB 457 in the left posterior cingulate cortex, but the analgesic effect of alfentanil did not correlate with changes in [(11)C]FLB 457 BP. The results of this study demonstrate opioid-dopamine interactions in frontal and temporal cortical regions and the thalamus in healthy subjects. Increased D2/D3 tracer binding during opioid infusion may reflect decreased synaptic dopamine levels. The association of the uplifting effect of alfentanil with increased D2/D3 binding in the posterior cingulate cortex suggests that cortical dopamine may be involved in the behavioral effects of opioids.

The novel neuropeptides orexin A and B are selectively synthesised in the lateral and posterior hypothalamus and are involved in hypothalamic regulation of autonomic and neuroendocrine functions. Recent findings point also to a role in nociception. As the posterior hypothalamus is involved in the central modulation of nociception we studied the effects of hypocretin/orexin receptor activation in the posterior hypothalamic area (PH) of the rat on dural nociceptive input. Orexins were microinjected into the PH and the effects on responses of neurones in the caudal trigeminal nucleus studied. Injection of orexin A decreased the A- and C-fibre responses to dural electrical stimulation as well as spontaneous activity. Responses to noxious thermal stimulation of the facial skin were also decreased by orexin A. Injection of orexin B into the PH, however, elicited increased responses to dural stimulation in A- and C-fibre responses and resulted in increased spontaneous activity. Responses to facial thermal stimulation were also increased by orexin B. Control injection of saline into the PH had no significant effect. The results show a differential modulation of dural nociceptive input by orexin A and B receptor activation in the PH. The results support the role of the PH in the nociceptive processing of meningeal input. As both peptides are also involved in hypothalamic regulation of neuroendocrine and autonomic functions, orexinergic mechanisms in the PH may provide a link for endocrine and autonomic changes as well as nociceptive phenomena seen in primary headache disorders.

Electrophysiological studies have revealed a source of laser pain evoked potentials (LEPs) in cingulate cortex. However, few studies have used realistically shaped head models in the source analysis, which account for individual differences in anatomy and allow detailed anatomical localisation of sources. The aim of the current study was to accurately localise the cingulate source of LEPs in a group of healthy volunteers, using realistic head models, and to assess the inter-individual variability in anatomical location. LEPs, elicited by painful CO(2) laser stimulation of the right forearm, were recorded from 62 electrodes in five healthy subjects. Dipole source localisation (CURRY 4.0) was performed on the most prominent (P2) peak of each LEP data set, using head models derived from each subject's structural magnetic resonance image (MRI).For all subjects, the P2 LEP peak was best explained by a dipole whose origin was in cingulate cortex (mean residual variance was 3.9+/-2.4 %). For four out of five subjects, it was located at the border of the caudal division of left anterior cingulate cortex (area 24/32') with left posterior cingulate cortex (area 23/31). For the fifth subject the dipole was centred in right posterior cingulate cortex (area 31). This study demonstrates that the location of the cingulate source of LEPs is highly consistent across subjects, when analysed in this way, and supports the involvement of caudal cingulate regions in pain processing.

The study design is a cross-sectional survey with psychometric analysis. The objective is to determine the validity of a modified version of the Short-Form McGill Pain Questionnaire (SF-MPQ). The SF-MPQ has been widely used to differentiate between reports of sensory and affective pain. The validity of this instrument to reflect independence between these constructs remains unclear. The SF-MPQ, the Roland-Morris Questionnaire (RM) and a measure of current pain intensity were completed by 373 patients undergoing lumbar magnetic resonance imaging (MRI). Four hypothesized factor structures for the SF-MPQ (three 2-factor and one 1-factor solution) were tested using confirmatory factor analysis. A modified 2-factor solution (MSF-MPQ) containing 3 items labeled sensory and 5 items labeled affective-sensory had the best degree of fit. Correlations between factors were substantially lower for the modified 2-factor solution (0.48) than for previously described 2-factor solutions (0.88 and 0.92) indicating a higher degree of independence between these factors. Correlations with measures of pain intensity and the RM were significant, but slightly lower, for the subscales of the modified 2-factor solution (0.26-0.40) than for the subscales of the previously described 2-factor solutions (0.34-0.45). The MSF-MPQ can be used as a brief tool to differentiate the language used to describe pain in patients who are undergoing lumbar MRI. The evidence indicates that this clinical tool can be used to categorize how these patients describe their pain and potentially may be very valuable in determining the optimal course of treatment.

Tissue damage during surgery can induce 'central sensitization' and the development of pain and hyperalgesia post-operatively. Metabotropic glutamate receptors (mGluRs) contribute to nociception, inflammatory pain and hyperalgesia. This study characterized the temporal expression of group I (mGluR(1), mGluR(5)) and II (mGluR(2), mGluR(3)) mGluRs in spinal cord following abdominal surgery. Lumbar spinal cord was recovered from adult sheep euthanased 5 h, 1, 2, 3 and 6 days after undergoing a midline laparotomy, and processed for mGluR mRNA (real-time PCR, in situ hybridization) and protein (Western blotting). mGluR(5) mRNA was up-regulated 5 h and 1 day post-surgery in laminae I-II of the spinal cord dorsal horn. mGluR(5) protein was increased 1 day post-surgery. A delayed induction of mGluR(2) and mGluR(3) mRNAs and mGluR(2/3) protein occurred in spinal cord 3 days after surgery. By 6 days, mGluR(2) mRNA levels had returned to normal, however, mGluR(3) mRNA and mGluR(2/3) protein remained elevated. No change was detected in mGluR(1). These results demonstrate that mGluRs are differentially regulated following surgery and support a link between mGluR-mediated activity and post-surgical pain.

We investigated adverse events (AEs) associated with perioperative tenoxicam in a double-blind, prospective, randomised study. Patients undergoing surgery, screened for contraindications to non-steroidal anti-inflammatory drug, received tenoxicam (n=750) on 2843 days or placebo (n=251) on 988 days, in courses of 1-12 days. There was no increase in the overall incidence of side effects with tenoxicam (33 vs 38% with placebo: P=0.15), or in major side effects (3.9 vs 2.0% with placebo: P=0.11). Of major side effects possibly or probably related to tenoxicam (2.1 vs 1.2% with placebo: P=0.26), all but one involved post-operative surgical site bleeding. However, in the subgroup of patients undergoing otorhinolaryngology surgery, surgical site bleeding occurred in 18 of 171 (10.5%) patients on tenoxicam and one of 57 (1.8%) on placebo (P=0.026); of these, nine in the tenoxicam group and 0 in the placebo were classified as major (P=0.07). One patient on tenoxicam experienced endoscopically proven duodenal ulceration with malaena. In conclusion, perioperative tenoxicam is well tolerated in comparison with placebo and the incidence of drug-related major AEs (other than post-operative bleeding) is no greater than 1 in 150 in low risk patients, but in patients undergoing otorhinolaryngological surgery there may be an increased risk of post-operative bleeding.

Over the years, many have viewed Fibromyalgia syndrome (FMS) as a so-called "functional disorder" and patients have experienced a concomitant lack of interest and legitimacy from the medical profession. The symptoms have not been explained by peripheral mechanisms alone nor by specific central nervous system mechanisms. In this study, we objectively evaluated the cerebral response to individually calibrated pain provocations of a pain-free body region (thumbnail). The study comprised 16 female FMS patients and 16 individually age-matched controls. Brain activity was measured using functional magnetic resonance imaging (fMRI) during individually calibrated painful pressures representing 50 mm on a visual analogue scale (VAS) ranging from 0 to 100 mm. Patients exhibited higher sensitivity to pain provocation than controls as they required less pressure to evoke equal pain magnitudes (U(A)=48, p<.002). Despite lower pressures applied in patients at VAS 50 mm, the fMRI-analysis revealed no difference in activity in brain regions relating to attention and affect or regions with sensory projections from the stimulated body area. However, in the primary link in the descending pain regulating system (the rostral anterior cingulate cortex) the patients failed to respond to pain provocation. The attenuated response to pain in this brain region is the first demonstration of a specific brain region where the impairment of pain inhibition in FMS patients is expressed. These results validate previous reports of dysfunctional endogenous pain inhibition in FMS and advance the understanding of the central pathophysiologic mechanisms, providing a new direction for the development of successful treatments in FMS.

Somatisation is often invoked to explain pain and suffering in patients. Lipowski [34] defined somatisation as "a tendency to experience and communicate somatic distress and symptoms unaccounted for by pathological findings, to attribute them to physical illness, and to seek medical help for them" (p. 1359). His concept is widely accepted. This study investigated to what extent this conceptualisation is used in the empirical studies of pain. Studies were identified through searches from Web of Science, Pubmed and Psychinfo databases for the period from 1989 until 2007. Screening an initial set of 1020 articles resulted in 120 articles fulfilling inclusion criteria. One hundred and sixteen articles were retrieved and coded in terms of the conceptualisation of Lipowski [34]. All studies had a measure of somatic symptoms, most often questionnaires. Whether the symptoms were unaccounted for by pathological findings was rarely investigated. No study assessed whether the participants attributed the somatic complaints to physical illness. Most studies included patients seeking help in a clinical setting, but only one study investigated whether patients were seeking help for the somatisation complaints. In conclusion, no study fulfilled the construct criteria as defined by Lipowski [34]. Most studies focus upon the extent and diversity of somatic complaints. We recommend that researchers who use self-report instruments do not use the term "somatisation" (even if the instrument is labeled as a "somatisation" scale), but use the term "multiple physical symptoms" instead. The current operational use may unduly lead to a "psychologisation" of physical complaints.

The selection of outcome criteria for chronic pain, both the domain of measurement and the magnitude of change, in RCTs is largely determined by the investigators. The present study investigated patient-determined criteria for the magnitude of change necessary to achieve an 'acceptable outcome' (endpoint) on the brief pain inventory and two subscales of the multidimensional pain inventory. Seventy-eight patients attending a chronic pain out-patient clinic were asked to rate their current state on the measures and then complete the scales as they would if treatment were to result in an acceptable outcome. The differences between the two sets of scores are described in terms of raw change scores, percentage change and by comparing the judgments of acceptable outcomes to statistically defined criteria (reliable change index and clinically significant change). Participants indicated a lower level of pain severity, impact and interference and a higher level of activity as part of an acceptable outcome. The degree of acceptable changes indicated by participants was higher (median values=44-75%) than the 30-50% typically reported as the threshold for clinically significant change for measures of pain experience in other studies. We also conducted tests of two models of change judgment. Neither adequately fit the data. There were discrepancies between the patients' judgments of acceptable outcomes and the RCI and SCS criteria. Suggestions for future research and possible clinical implications are discussed.

The involvement of TRPV1 and TRPA1 in mediating craniofacial muscle nociception and mechanical hyperalgesia was investigated in male Sprague-Dawley rats. First, we confirmed the expression of TRPV1 in masseter afferents in rat trigeminal ganglia (TG), and provided new data that TRPA1 is also expressed in primary afferents innervating masticatory muscles in double-labeling immunohistochemistry experiments. We then examined whether the activation of each TRP channel in the masseter muscle evokes acute nocifensive responses and leads to the development of masseter hypersensitivity to mechanical stimulation using the behavioral models that have been specifically designed and validated for the craniofacial system. Intramuscular injections with specific agonists for TRPV1 and TRPA1, capsaicin and mustard oil (MO), respectively, produced immediate nocifensive hindpaw responses followed by prolonged mechanical hyperalgesia in a concentration-dependent manner. Pretreatment of the muscle with a TRPV1 antagonist, capsazepine, effectively attenuated the capsaicin-induced muscle nociception and mechanical hyperalgesia. Similarly, pretreatment of the muscle with a selective TRPA1 antagonist, AP18, significantly blocked the MO-induced muscle nociception and mechanical hyperalgesia. We confirmed these data with another set of selective antagonist for TRPV1 and TRPA1, AMG9810 and HC030031, respectively. Collectively, these results provide compelling evidence that TRPV1 and TRPA1 can functionally contribute to muscle nociception and hyperalgesia, and suggest that TRP channels expressed in muscle afferents can engage in the development of pathologic muscle pain conditions.

Neural, endocrine, and immune stress mediators are hypothesized to increase risks of diverse chronic diseases, including arthritis. Retrospective data from the World Mental Health Surveys (N=18,309) were employed to assess whether adult onset of arthritis was associated with childhood adversities and early onset psychological disorder. Cox proportional hazard models assessed the association of number of childhood adversities and the presence of early onset psychological disorder with arthritis age of onset. Controlling for age, sex, and early onset mental disorder, relative to persons with no childhood adversities, persons with two adversities had an increased risk of adult onset arthritis (hazard ratio=1.27, 95% CI=1.08, 1.50), while persons with three or more adversities had a higher risk (HR=1.44, CI=1.24, 1.67). Early onset depressive and/or anxiety disorder was associated with an increased risk of adult onset arthritis after controlling for childhood adversities (HR=1.43, CI=1.28, 1.61). Since psychosocial stressors may be broad spectrum risk factors that increase risks of diverse chronic conditions in later life (e.g. arthritis, heart disease, diabetes, asthma, and chronic pain), prospective studies of childhood psychosocial stressors may be most productive if multiple disease outcomes are assessed in the same study. Results from this study provide methodological guidance for future prospective studies of the relationship between childhood psychosocial stressors and subsequent risk of adult onset arthritis.

To explore cellular changes in sensory neurons after nerve injury and to identify potential target genes contributing to different stages of neuropathic pain development, we used Affymetrix oligo arrays to profile gene expression patterns in L5/6 dorsal root ganglia (DRG) from the neuropathic pain model of left L5/6 spinal nerve ligation at different stages of neuropathic pain development. Our data indicated that nerve injury induced changes in expression of genes with similar biological functions in a temporal specific manner that correlates with particular stages of neuropathic pain development, indicating dynamic neuroplasticity in the DRG in response to peripheral nerve injury and during neuropathic pain development. Data from post-array validation indicated that there was a temporal correlation between injury-induced expression of the glial fibrillary acidic protein (GFAP), a marker for activated astrocytes, and neuropathic pain development. Spinal nerve ligation injury in GFAP knockout mice resulted in neuropathic pain states with similar onset, but a shortened duration compared with that in age, and gender-matched wild-type littermates. Intrathecal GFAP antisense oligonucleotide treatment in injured rats with neuropathic pain states reversed injury-induced behavioral hypersensitivity and GFAP upregulation in DRG and spinal cord. Together, these findings indicate that injury-induced GFAP upregulation not only serves as a marker for astrocyte activation, but it may also play a critical, but yet identified, role in the maintenance of neuropathic pain states.

Sensory neuron-specific receptors (SNSRs) belong to a large family of GPCRs, known as Mrgs (Mas-related genes), many of which are preferentially expressed in primary afferent nociceptors. Selective SNSR agonists produce pain-like behaviors in rats, showing that SNSR activation is sufficient to produce pain. However, it is unknown whether SNSR activation is necessary for pain either in the normal condition or in pathological pain states. Here we used small interfering RNA (siRNA) to acutely knockdown rat SNSR1 and test the hypothesis that this receptor mediates pain responses. Administration of siRNA to the lumbar spinal cord in rats dose-dependently knocked down rSNSR1 mRNA and protein and abolished heat hyperalgesia evoked by intradermal administration of specific rSNSR1 agonists. In rats with levels of rSNSR1 knockdown sufficient to block responses to the SNSR1 agonists, there was no effect on normal pain responses, but there was a significant reduction of heat hyperalgesia in an inflammatory pain model (Complete Freund's Adjuvant), supporting a role for rSNSR1 in inflammatory pain. Further in vivo studies revealed that SNSR1 knockdown had no effect on responses to intradermal capsaicin, a selective TRPV1 agonist. In contrast, a selective TRPV1 antagonist abolished heat hyperalgesia produced by an SNSR agonist, suggesting that TRPV1 receptors mediate rSNSR1-evoked responses. We also found that rSNSR1-like immunoreactivity, like TRPV1, is localized in the superficial dorsal horn of the spinal cord. We propose that rSNSR1 represents a new member of the receptors expressed on chemosensitive nociceptors responsible for detecting the "inflammatory soup" of mediators generated by tissue damage.

Fibromyalgia (FM) is thought to involve abnormalities in central pain processing. Recent studies involving small samples have suggested alterations in gray matter volume (GMV) in brains of FM patients. Our objective was to verify these findings in a somewhat larger sample using voxel-based morphometry (VBM), while controlling for the presence of affective disorders (AD). T1-weighted magnetic resonance image (MRI) brain scans were obtained on 29 FM patients with AD, 29 FM patients without AD, and 29 age-matched healthy controls (HCs) using a 3T scanner. Segmentation, spatial normalization, and volumetric modulation were performed using an automated protocol within SPM5. Smoothed gray matter segments were entered into a voxel-wise one-way ANOVA, and a search for significant clusters was performed using thresholding methods published in previous studies (whole-brain threshold of p<.05 correcting for multiple comparisons; region-of-interest (ROI) threshold of p< or =.001 uncorrected, or p<.05 small-volume corrected). The whole-brain analysis did not reveal any significant clusters. ROI-based analysis revealed a significant difference in left anterior insula GMV among the three groups (xyz={-28, 21, 9}; p=.026, corrected). However, on post-hoc testing, FM patients without AD did not differ significantly from HC with respect to mean GMV extracted from this cluster. A significant negative correlation was found between mean cluster GMV and scores of trait anxiety (State-Trait Personality Inventory, Trait Anxiety scale; rho=-.470, p<.001). No other significant clusters were found on ROI-based analysis. Our results emphasize the importance of correcting for AD when carrying out VBM studies in chronic pain.

Gangliosides are abundant in neural tissue and play important roles in cell-cell adhesion, signal transduction, and cell differentiation. Gangliosides are divided into 4 groups: asialo-, a-, b-, and c-series gangliosides, based on their biosynthetic pathway. St8sia1 knockout mice, which lack b- and c-series gangliosides, exhibit altered nociceptive responses. The mechanism underlying this defect, however, remains unclear. To address this issue, we first investigated the possibility that gangliosides in peripheral nociceptor endings are involved in nociception. Intraplantar injection of the b-series ganglioside GT1b, but not a-series gangliosides such as GM1, produced nociceptive responses and enhanced low-concentration formalin-induced nociception. N-methyl-d-aspartic acid receptor and type I metabotropic glutamate receptor antagonists inhibited GT1b-induced hyperalgesia, suggesting the involvement of glutamate receptors. Furthermore, microdialysis analysis revealed elevated glutamate content in subdermal tissues due to intraplantar injection of GT1b. Co-injection of glutamate dehydrogenase with GT1b attenuated GT1b-induced hyperalgesia. These findings suggested that GT1b induced extracellular glutamate to accumulate in subdermal tissues, thereafter activating glutamate receptors, which in turn resulted in hyperalgesia and nociception. On the other hand, intraplantar injection of sialidase, which cleaves sialyl residues from glycoconjugates such as gangliosides, attenuated the late phase of 2% formalin-induced nociception. Thus, the antinociceptive effects of sialidase and the nociceptive effects of GT1b indicated that endogenous gangliosides are involved in nociceptive responses. These results suggest that gangliosides play important roles in nociceptive responses originating in peripheral nociceptor endings. Ganglioside GT1b induced extracellular glutamate to accumulate in subdermal tissues, thereafter activating glutamate receptors, which in turn resulted in hyperalgesia and nociception.

Mindfulness-based stress reduction (MBSR) is a structured 8-week group program teaching mindfulness meditation and mindful yoga exercises. MBSR aims to help participants develop nonjudgmental awareness of moment-to-moment experience. Fibromyalgia is a clinical syndrome with chronic pain, fatigue, and insomnia as major symptoms. Efficacy of MBSR for enhanced well-being of fibromyalgia patients was investigated in a 3-armed trial, which was a follow-up to an earlier quasi-randomized investigation. A total of 177 female patients were randomized to one of the following: (1) MBSR, (2) an active control procedure controlling for nonspecific effects of MBSR, or (3) a wait list. The major outcome was health-related quality of life (HRQoL) 2 months post-treatment. Secondary outcomes were disorder-specific quality of life, depression, pain, anxiety, somatic complaints, and a proposed index of mindfulness. Of the patients, 82% completed the study. There were no significant differences between groups on primary outcome, but patients overall improved in HRQoL at short-term follow-up (P=0.004). Post hoc analyses showed that only MBSR manifested a significant pre-to-post-intervention improvement in HRQoL (P=0.02). Furthermore, multivariate analysis of secondary measures indicated modest benefits for MBSR patients. MBSR yielded significant pre-to-post-intervention improvements in 6 of 8 secondary outcome variables, the active control in 3, and the wait list in 2. In conclusion, primary outcome analyses did not support the efficacy of MBSR in fibromyalgia, although patients in the MBSR arm appeared to benefit most. Effect sizes were small compared to the earlier, quasi-randomized investigation. Several methodological aspects are discussed, e.g., patient burden, treatment preference and motivation, that may provide explanations for differences. In a 3-armed randomized controlled trial in female patients suffering from fibromyalgia, patients benefited modestly from a mindfulness-based stress reduction intervention.

Pain management in elderly people with cognitive impairment poses special challenges, due to difficulties in pain assessment and specific neurodegenerative changes along pain pathways. Most studies have concentrated on Alzheimer's disease (AD) patients, in whom some contrasting findings have been found. For example, while psychophysical data suggest a selective blunting of the affective dimension of pain, pain-related fMRI signal increases have also been described. Few data have been reported in patients with frontotemporal dementia (FTD). By electrical stimulation, we have measured pain threshold and pain tolerance in clinically diagnosed FTD patients with SPECT cerebral hypoperfusion. We performed our analysis on two separate and overlapping subgroups selected on the basis of (1) neuropsychological scores below cut-off values (2) a strictly localized frontal and/or temporal hypoperfusion. We observed increased pain threshold in the first group and increased pain threshold and pain tolerance in the second group. Our results suggest differences in pain processing changes in distinct types of dementia, while at the same time caution that pain perception assessment may depend on the criteria adopted for diagnosis.