Spontaneous migraine attack causes alterations in default mode network connectivity

BACKGROUND: Although migraine is one of the most investigated neurologic disorders, we do not have a perfect neuroimaging biomarker for its pathophysiology. One option to improve our knowledge is to study resting-state functional connectivity in and out of headache pain. However, our understanding of the functional connectivity changes during spontaneous migraine attack is partial and incomplete. CASE PRESENTATION: Using resting-state functional magnetic resonance imaging we assessed a 24-year old woman affected by migraine without aura at two different times: during a spontaneous migraine attack and in interictal phase. Seed-to-voxel whole brain analysis was carried out using the posterior cingulate cortex as a seed, representing the default mode network (DMN). Our results showed decreased intrinsic connectivity within core regions of the DMN with an exception of a subsystem including the dorsal medial and superior frontal gyri, and the mid-temporal gyrus which is responsible for pain interpretation and control. In addition, increased connectivity between the DMN and pain and specific migraine-related areas, such as the pons and hypothalamus, developed during the spontaneous migraine attack. CONCLUSION: Our preliminary results provide further support for the hypothesis that alterations of the DMN functional connectivity during migraine headache may lead to maladaptive top-down modulation of migraine pain-related areas which might be a specific biomarker for migraine

Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue Conditioning and Their Association

Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol), sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for “placebo responders.” However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non-specific effects of acupuncture may contribute to the analgesic effect observed in genuine acupuncture analgesia.National Center for Complementary and Alternative Medicine (U.S.) (R01AT005280

Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain

BACKGROUND: The mechanism(s) of nociceptive dysfunction and potential roles of opioid neurotransmitters are unresolved in the chronic pain syndromes of fibromyalgia and chronic low back pain. METHODS: History and physical examinations, tender point examinations, and questionnaires were used to identify 14 fibromyalgia, 10 chronic low back pain and 6 normal control subjects. Lumbar punctures were performed. Met-enkephalin-Arg(6)-Phe(7 )(MEAP) and nociceptin immunoreactive materials were measured in the cerebrospinal fluid by radioimmunoassays. RESULTS: Fibromyalgia (117.6 pg/ml; 85.9 to 149.4; mean, 95% C.I.; p = 0.009) and low back pain (92.3 pg/ml; 56.9 to 127.7; p = 0.049) groups had significantly higher MEAP than the normal control group (35.7 pg/ml; 15.0 to 56.5). MEAP was inversely correlated to systemic pain thresholds. Nociceptin was not different between groups. Systemic Complaints questionnaire responses were significantly ranked as fibromyalgia > back pain > normal. SF-36 domains demonstrated severe disability for the low back pain group, intermediate results in fibromyalgia, and high function in the normal group. CONCLUSIONS: Fibromyalgia was distinguished by higher cerebrospinal fluid MEAP, systemic complaints, and manual tender points; intermediate SF-36 scores; and lower pain thresholds compared to the low back pain and normal groups. MEAP and systemic pain thresholds were inversely correlated in low back pain subjects. Central nervous system opioid dysfunction may contribute to pain in fibromyalgia

Mapping Brain Response to Pain in Fibromyalgia Patients Using Temporal Analysis of fMRI

Background: Nociceptive stimuli may evoke brain responses longer than the stimulus duration often partially detected by conventional neuroimaging. Fibromyalgia patients typically complain of severe pain from gentle stimuli. We aimed to characterize brain response to painful pressure in fibromyalgia patients by generating activation maps adjusted for the duration of brain responses. Methodology/Principal Findings: Twenty-seven women (mean age: 47.8 years) were assessed with fMRI. The sample included nine fibromyalgia patients and nine healthy subjects who received 4 kg/cm2 of pressure on the thumb. Nine additional control subjects received 6.8 kg/cm2 to match the patients for the severity of perceived pain. Independent Component Analysis characterized the temporal dynamics of the actual brain response to pressure. Statistical parametric maps were estimated using the obtained time courses. Brain response to pressure (18 seconds) consistently exceeded the stimulus application (9 seconds) in somatosensory regions in all groups. fMRI maps following such temporal dynamics showed a complete pain network response (sensory-motor cortices, operculo-insula, cingulate cortex, and basal ganglia) to 4 kg/cm2 of pressure in fibromyalgia patients. In healthy subjects, response to this low intensity pressure involved mainly somatosensory cortices. When matched for perceived pain (6.8 kg/cm2), control subjects showed also comprehensive activation of pain-related regions, but fibromyalgia patients showed significantly larger activation in the anterior insula-basal ganglia complex and the cingulate cortex. Conclusions/Significance: The results suggest that data-driven fMRI assessments may complement conventional neuroimaging for characterizing pain responses and that enhancement of brain activation in fibromyalgia patients may be particularly relevant in emotion-related regions

Hypnotic analgesia reduces brain responses to pain seen in others.

Brain responses to pain experienced by oneself or seen in other people show consistent overlap in the pain processing network, particularly anterior insula, supporting the view that pain empathy partly relies on neural processes engaged by self-nociception. However, it remains unresolved whether changes in one's own pain sensation may affect empathic responding to others' pain. Here we show that inducing analgesia through hypnosis leads to decreased responses to both self and vicarious experience of pain. Activations in the right anterior insula and amygdala were markedly reduced when participants received painful thermal stimuli following hypnotic analgesia on their own hand, but also when they viewed pictures of others' hand in pain. Functional connectivity analysis indicated that this hypnotic modulation of pain responses was associated with differential recruitment of right prefrontal regions implicated in selective attention and inhibitory control. Our results provide novel support to the view that self-nociception is involved during empathy for pain, and demonstrate the possibility to use hypnotic procedures to modulate higher-level emotional and social processes

Autonomic neuropathy in Fabry disease: a prospective study using the Autonomic Symptom Profile and cardiovascular autonomic function tests

<p>Abstract</p> <p>Background</p> <p>Fabry patients have symptoms and signs compatible with autonomic dysfunction. These symptoms and signs are considered to be due to impairment of the peripheral nervous system, but findings indicative of autonomic neuropathy in other diseases, such as orthostatic intolerance and male sexual dysfunction, are infrequently reported in Fabry disease. The aim of our study was to investigate autonomic symptoms and cardiovascular autonomic function in a large cohort of male and female Fabry patients.</p> <p>Methods</p> <p>Forty-eight Fabry patients (15 male, 30 treated with enzyme replacement therapy) and 48 sex- and age-matched controls completed a questionnaire on autonomic symptoms (the Autonomic Symptom Profile). Thirty-six Fabry patients underwent cardiovascular function tests.</p> <p>Results</p> <p>The Autonomic Symptom Profile revealed a significantly higher sum score in Fabry patients than in healthy control subjects (22 versus 12), but a relatively low score compared to patients with proven autonomic neuropathy. Fabry patients scored worse than healthy controls in the orthostatic intolerance domain. Scores in the male sexual dysfunction domain were comparable between healthy controls and male Fabry patients. The cardiovascular autonomic function tests revealed only mild abnormalities in seven patients. None of these seven patients showed more than one abnormal test result. Enzyme replacement therapy was not associated with less severe disease, lower ASP scores or less frequent abnormal cardiovascular function test results.</p> <p>Conclusions</p> <p>Male sexual function and autonomic control of the cardiovascular system are nearly normal in Fabry patients, which cast doubt on the general accepted assumption that autonomic neuropathy is the main cause of symptoms and signs compatible with autonomic dysfunction in Fabry disease. Possibly, end-organ damage plays a key role in the development of symptoms and signs in Fabry patients. An exceptional kind of autonomic neuropathy is another but less likely explanation.</p

Changes in catastrophizing and kinesiophobia are predictive of changes in disability and pain after treatment in patients with anterior knee pain

Purpose. The purpose of the study was to investigate if changes in psychological variables are related to the outcome in pain and disability in patients with chronic anterior knee pain. Methods. A longitudinal observational study on 47 patients with chronic anterior knee pain was performed in a secondary healthcare setting. Pain was measured with the visual analogue scale and disability with the Lysholm scale. The psychological variables, such as anxiety, depression, pain coping strategies, catastrophizing and fear to movement beliefs, were studied by using self-administered questionnaires. Results. Among the pain coping strategies, only the catastrophizing subscale showed a significant reduction. Similarly, anxiety, depression and kinesiophobia were significantly reduced after treatment. Those patients who decreased the catastrophizing, kinesiophobia, anxiety and depression showed a greater improvement in pain and disability after a purely biomedical treatment. A multiple regression analysis revealed that changes in catastrophizing predicted the amount of improvement in pain severity and that changes in both catastrophizing and anxiety predicted changes in disability after treatment. Conclusion. What has been found suggests that clinical improvement in pain and disability is associated with a reduction in catastrophizing and kinesiophobia. Therefore, co-interventions to reduce catastrophizing thinking and kinesiophobia may enhance the results. Level of evidence. Prospective Cohort Study, Level I for prognosis