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Fear of movement-related pain leads to two types of avoidance behavior: excessive avoidance and pain-inhibited movement. Excessive avoidance is an absence of movement by fear, and pain-inhibited movements involve a change in motor behavior for the purpose of protecting the painful part. Here, we sought to clarify the acquisition process and adaptation of fear for each avoidance behavior. Thirty-one female and 13 male (age 20.9 ± 2.1 years) subjects could decide persistent behaviors: approach with an intense pain stimulus, pain-inhibited movement with weak pain stimulus, or excessive avoidance with no pain in acquisition and test phases. In the subsequent extinction phase, the pain stimulus was omitted. Subjects were divided into an approach group ( = 24), a pain-inhibited movement group ( = 10), and an excessive avoidance group ( = 10) by cluster analysis. The response latencies in approach and pain-inhibited movement groups were not affected by conditioned pain. The subjects in the excessive avoidance group exhibited delayed response latencies, and their high-fear responses remained in the acquisition, test, and extinction phases. In addition, the excessive avoidance group showed high harm avoidance and high trait anxiety. This study demonstrated that differences in pain-related avoidance behaviors are affected by psychological traits. Pain-related excessive avoidance behavior indicated a maladaptive fear, but pain-inhibited movement did not.
Learn More >Brain structure and function were reported to be altered in migraine. Importantly our earlier results showed that white matter diffusion abnormalities and resting state functional activity were affected differently in the two subtypes of the disease, migraine with and without aura. Resting fluctuation of the BOLD signal in the white matter was reported recently. The question arising whether the white matter activity, that is strongly coupled with gray matter activity is also perturbed differentially in the two subtypes of the disease and if so, is it related to the microstructural alterations of the white matter. Resting state fMRI, 60 directional DTI images and high-resolution T1 images were obtained from 51 migraine patients and 32 healthy volunteers. The images were pre-processed and the white matter was extracted. Independent component analysis was performed to obtain white matter functional networks. The differential expression of the white matter functional networks in the two subtypes of the disease was investigated with dual-regression approach. The Fourier spectrum of the resting fMRI fluctuations were compared between groups. Voxel-wise correlation was calculated between the resting state functional activity fluctuations and white matter microstructural measures. Three white matter networks were identified that were expressed differently in migraine with and without aura. Migraineurs with aura showed increased functional connectivity and amplitude of BOLD fluctuation. Fractional anisotropy and radial diffusivity showed strong correlation with the expression of the frontal white matter network in patients with aura. Our study is the first to describe changes in white matter resting state functional activity in migraine with aura, showing correlation with the underlying microstructure. Functional and structural differences between disease subtypes suggest at least partially different pathomechanism, which may necessitate handling of these subtypes as separate entities in further studies.
Learn More >Pain medications are widely prescribed to treat chronic back pain (CBP). However, the effect of using pain medications on individuals with CBP has received very little attention.
Learn More >Plasma calcitonin gene-related peptide (CGRP) plays a key role in the migraine pathophysiology. This study aimed to investigate its role in predicting diagnosis and outcome of pharmacotherapy in pediatric migraine. We prospectively recruited 120 subjects, who never took migraine-preventive agents in a pediatric clinic, including 68 patients with migraine, 30 with non-migraine headache (NM), and 22 non-headache (NH) age-matched controls. Short-term therapeutic response was measured for at least 2 weeks after the start of therapy. Responders were defined with >50% headache reduction. Plasma CGRP concentrations were measured by ELISA. In the migraine group, more patients required acute therapy, as compared to the NM group (62/68, 91% vs. 5/30, 15%, = 0.001). The mean plasma CGRP level in migraineurs either during (291 ± 60 pg/ml) or between (240 ± 48) attacks was higher than in NM patients (51 ± 5 pg/ml, = 0.006 and 0.018, respectively) and NH controls (53 ± 6 pg/ml, = 0.016 and 0.045, respectively). Forty-seven patients (69%) needed preventive treatments and had higher plasma CGRP levels (364 ± 62 pg/ml, = 47) than those not (183 ± 54 pg/ml, = 21) ( = 0.031). Topiramate responders had higher plasma CGRP levels than non-responders (437 ± 131 pg/ml, = 14 vs. 67 ± 19 pg/ml, = 6, = 0.021). Survival curves of plasma CGRP levels also showed those with higher CGRP levels responded better to topiramate. Differences were not found in the other preventives. The plasma CGRP level can differentiate migraine from non-migraine headache. It may also serve as a reference for the therapeutic strategy since it is higher in patients requiring migraine prevention and responsive to short-term topiramate treatment. These results are clinically significant, especially for the young children who cannot clearly describe their headache symptoms and may provide new insights into the clinical practice for the diagnosis and treatment of pediatric migraine.
Learn More >Migraine and restless legs syndrome (RLS) are often comorbid and share elements of pathology; however, their neuroanatomical underpinnings are poorly understood. This study aimed to identify patterns of gray matter volume (GMV) alteration specific to and common among patients with RLS, migraine, and comorbid migraine and RLS.
Learn More >Dorsal root ganglion stimulation is an emerging therapy in the treatment of chronic pain. Compared with traditional spinal cord stimulation, it allows a discretely targeted stimulation profile and may act via differing mechanisms of action. Despite these advantages, little is known about the complications associated with this new modality.
Learn More >Pain experience involves a complex relationship between sensory and both emotional and cognitive factors, which appear to be mediated by different neural pathways. Previous evidence has shown that whereas conscious processing of unpleasant stimuli enhances pain perception, the influence of emotions on pain under unaware conditions is much less known. The need to better characterise the relationship between pain processing and emotional factors is crucial for dealing with chronic pain conditions. Therefore, the present study aimed to explore the neural correlates relating to the influence of visual masking emotional stimulation on the processing of painful stimuli in chronic pain patients suffering from fibromyalgia (FM). Twenty FM and 22 healthy control (HC) women participated in the study. The experimental masking paradigm consisted of a rapid succession of two types of stimuli, where a masked picture (neutral, negative or pain-related) was followed by a laser stimulus (painful or not painful). LEP activity was recorded at sixty scalp electrodes. An LEP-amplitude approach was used to quantify the main cerebral waves linked to pain response. ANOVAs indicated that the posterior regions of the P1 component were sensitive to experimental manipulation (p<0.05). Specifically, FM patients showed higher amplitudes to painful stimuli preceded by pain-related pictures compared with painful trials preceded by other emotional pictures. The FM group also showed greater amplitudes than those in the HC group in P2a and P2b waves. In addition to the scalp data, at the neural level the posterior cingulate cortex, lingual gyrus and insular cortex showed higher activation in the FM group than in the HC group. Our findings show an early cerebral modulation of pain (as reflected by the P1) in FM patients, suggesting that only pain-related information, even when it is unconsciously perceived, is capable to enhance exogenous (automatic) attention, increasing the neural activity involved in processing painful stimulation. Further research is needed to fully understand unconscious emotional influences on pain in fibromyalgia.
Learn More >Previous studies have demonstrated that migraine is associated with enhanced perception and altered cerebral processing of sensory stimuli. More recently, it has been suggested that this sensory hypersensitivity might reflect a more general enhanced response to aversive emotional stimuli. Using functional magnetic resonance imaging and emotional face stimuli (fearful, happy and sad faces), we compared whole-brain activation between 41 migraine patients without aura in interictal period and 49 healthy controls. Migraine patients showed increased neural activation to fearful faces compared to neutral faces in the right middle frontal gyrus and frontal pole relative to healthy controls. We also found that higher attack frequency in migraine patients was related to increased activation mainly in the right primary somatosensory cortex (corresponding to the face area) to fearful expressions and in the right dorsal striatal regions to happy faces. In both analyses, activation differences remained significant after controlling for anxiety and depressive symptoms. These findings indicate that enhanced response to emotional stimuli might explain the migraine trigger effect of psychosocial stressors that gradually leads to increased somatosensory response to emotional clues and thus contributes to the progression or chronification of migraine.
Learn More >Amputation of a sensory peripheral nerve induces severe anatomical and functional changes along the afferent pathway as well as perception alterations and neuropathic pain. In previous studies we showed that electrical stimulation applied to a transected infraorbital nerve protects the somatosensory cortex from the above-mentioned sensory deprivation-related changes. In the present study we focus on the initial tract of the somatosensory pathway and we investigate the way weak electrical stimulation modulates the neuroprotective-neuroregenerative and functional processes of trigeminal ganglia primary sensory neurons by studying the expression of neurotrophins (NTFs) and Glia-Derived Neurotrophic Factors (GDNFs) receptors. Neurostimulation was applied to the proximal stump of a transected left infraorbitary nerve using a neuroprosthetic micro-device 12 h/day for 4 weeks in freely behaving rats. Neurons were studied by hybridization and immunohistochemistry against RET (proto-oncogene tyrosine kinase "rearranged during transfection"), tropomyosin-related kinases (TrkA, TrkB, TrkC) receptors and IB4 (Isolectin B4 from Griffonia simplicifolia). Intra-group (left vs. right ganglia) and inter-group comparisons (between Control, Axotomization and Stimulation-after-axotomization groups) were performed using the mean percentage change of the number of positive cells per section [100(left-right)/right)]. Intra-group differences were studied by paired -tests. For inter-group comparisons ANOVA test followed by LSD test (when < 0.05) were used. Significance level (α) was set to 0.05 in all cases. Results showed that (i) neurostimulation has heterogeneous effects on primary nociceptive and mechanoceptive/proprioceptive neurons; (ii) neurostimulation affects RET-expressing small and large neurons which include thermo-nociceptors and mechanoceptors, as well as on the IB4- and TrkB-positive populations, which mainly correspond to non-peptidergic thermo-nociceptive cells and mechanoceptors respectively. Our results suggest (i) electrical stimulation differentially affects modality-specific primary sensory neurons (ii) artificial input mainly acts on specific nociceptive and mechanoceptive neurons (iii) neuroprosthetic stimulation could be used to modulate peripheral nerve injuries-induced neuropathic pain. These could have important functional implications in both, the design of effective clinical neurostimulation-based protocols and the development of neuroprosthetic devices, controlling primary sensory neurons through selective neurostimulation.
Learn More >Chiropractic maintenance care is effective as secondary/tertiary prevention of non-specific low back pain (LBP), but the potential effect moderation by psychological characteristics is unknown. The objective was to investigate whether patients in specific psychological sub-groups had different responses to MC with regard to the total number of days with bothersome pain and the number of treatments.
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