Single subject pharmacological-MRI (phMRI) study: Modulation of brain activity of psoriatic arthritis pain by cyclooxygenase-2 inhibitor

We use fMRI to examine brain activity for pain elicited by palpating joints in a single patient suffering from psoriatic arthritis. Changes in these responses are documented when the patient ingested a single dose of a selective cyclooxygenase-2 inhibitor (COX-2i). We show that mechanical stimulation of the painful joints exhibited a cortical activity pattern similar to that reported for acute pain, with activity primarily localized to the thalamus, insular, primary and secondary somatosensory cortices and the mid anterior cingulum. COX-2i resulted in significant decreased in reported pain intensity and in brain activity after 1 hour of administration. The anterior insula and SII correlated with pain intensity, however no central activation site for the drug was detected. We demonstrate the similarity of the activation pattern for palpating painful joints to brain activity in normal subjects in response to thermal painful stimuli, by performing a spatial conjunction analysis between these maps, where overlap is observed in the insula, thalamus, secondary somatosensory cortex, and anterior cingulate. The results demonstrate that one can study effects of pharmacological manipulations in a single subject where the brain activity for a clinical condition is delineated and its modulation by COX-2i demonstrated. This approach may have diagnostic and prognostic utility

Reorganization of functional brain network architecture in chronic osteoarthritis pain

Osteoarthritis (OA) manifests with chronic pain, motor impairment, and proprioceptive changes. However, the role of the brain in the disease is largely unknown. Here, we studied brain networks using the mathematical properties of graphs in a large sample of knee and hip OA (KOA, n = 91; HOA, n = 23) patients. We used a robust validation strategy by subdividing the KOA data into discovery and testing groups and tested the generalizability of our findings in HOA. Despite brain global topological properties being conserved in OA, we show there is a network wide pattern of reorganization that can be captured at the subject-level by a single measure, the hub disruption index. We localized reorganization patterns and uncovered a shift in the hierarchy of network hubs in OA: primary sensory and motor regions and parahippocampal gyrus behave as hubs and insular cortex loses its central placement. At an intermediate level of network structure, frontoparietal and cingulo-opercular modules showed preferential reorganization. We examined the association between network properties and clinical correlates: global disruption indices and isolated degree properties did not reflect clinical parameters; however, by modeling whole brain nodal degree properties, we identified a distributed set of regions that reliably predicted pain intensity in KOA and generalized to hip OA. Together, our findings reveal that while conserving global topological properties, brain network architecture reorganizes in OA, at both global and local scale. Network connectivity related to OA pain intensity is dissociated from the major hub disruptions, challenging the extent of dependence of OA pain on nociceptive signaling.CCDRN, Grant/Award Number: Norte‐08‐5369‐FSE‐000026; Unilabs Boavista and the Grünenthal Young Pain Researcher 2017 Grant; Luso‐American Development Foundation R&D@PhD Scholarship Grant; OARSI Collaborative Scholarship 201

The autonomic brain: Multi-dimensional generative hierarchical modelling of the autonomic connectome.

The autonomic nervous system governs the body's multifaceted internal adaptation to diverse changes in the external environment, a role more complex than is accessible to the methods-and data scales-hitherto used to illuminate its operation. Here we apply generative graphical modelling to large-scale multimodal neuroimaging data encompassing normal and abnormal states to derive a comprehensive hierarchical representation of the autonomic brain. We demonstrate that whereas conventional structural and functional maps identify regions jointly modulated by parasympathetic and sympathetic systems, only graphical analysis discriminates between them, revealing the cardinal roles of the autonomic system to be mediated by high-level distributed interactions. We provide a novel representation of the autonomic system-a multidimensional, generative network-that renders its richness tractable within future models of its function in health and disease

The autonomic brain: multi-dimensional generative hierarchical modelling of the autonomic connectome

The autonomic nervous system governs the body's multifaceted internal adaptation to diverse changes in the external environment, a role more complex than is accessible to the methods — and data scales — hitherto used to illuminate its operation. Here we apply generative graphical modelling to large-scale multimodal neuroimaging data encompassing normal and abnormal states to derive a comprehensive hierarchical representation of the autonomic brain. We demonstrate that whereas conventional structural and functional maps identify regions jointly modulated by parasympathetic and sympathetic systems, only graphical analysis discriminates between them, revealing the cardinal roles of the autonomic system to be mediated by high-level distributed interactions. We provide a novel representation of the autonomic system — a multidimensional, generative network — that renders its richness tractable within future models of its function in health and disease

Neurodegenerative Properties of Chronic Pain: Cognitive Decline in Patients with Chronic Pancreatitis

Chronic pain has been associated with impaired cognitive function. We examined cognitive performance in patients with severe chronic pancreatitis pain. We explored the following factors for their contribution to observed cognitive deficits: pain duration, comorbidity (depression, sleep disturbance), use of opioids, and premorbid alcohol abuse. The cognitive profiles of 16 patients with severe pain due to chronic pancreatitis were determined using an extensive neuropsychological test battery. Data from three cognitive domains (psychomotor performance, memory, executive functions) were compared to data from healthy controls matched for age, gender and education. Multivariate multilevel analysis of the data showed decreased test scores in patients with chronic pancreatitis pain in different cognitive domains. Psychomotor performance and executive functions showed the most prominent decline. Interestingly, pain duration appeared to be the strongest predictor for observed cognitive decline. Depressive symptoms, sleep disturbance, opioid use and history of alcohol abuse provided additional explanations for the observed cognitive decline in some of the tests, but to a lesser extent than pain duration. The negative effect of pain duration on cognitive performance is compatible with the theory of neurodegenerative properties of chronic pain. Therefore, early and effective therapeutic interventions might reduce or prevent decline in cognitive performance, thereby improving outcomes and quality of life in these patients

The formation of Fe-Cu composite based on bimetallic nanoparticles

In this paper we suggest a new method of producing a Fe-28 wt% Cu composite by compacting and subsequent sintering of bimetallic nanoparticles made of metals with limited mutual miscibility: iron and copper. The influence of the temperature of annealing on the structure and phase composition of consolidated composite samples has been analyzed. It has been shown that annealing in the temperature range of 200–400 °C induces the processes of low-temperature sintering of copper and iron. These processes are accompanied by the growth of the size of coherent scattering regions and the separation of the metallic components of nanoparticles. During thermal treatment in the range between 400 and 600 °C, adjacent sidewalls of large particles are welded together and large pores emerge in the sample. Further temperature increases cause the sample to shrink and the pores to become smaller. The consolidation of bimetallic nanoparticles consisting of iron and copper and their subsequent sintering allows for obtaining volumetric composites that have homogeneous structure without distinct macroscopic separation of phases as well as high strength characteristics.Russian Science Foundatio

Basal cutaneous pain threshold in headache patients

The aim of this study was to analyze cutaneous pain threshold (CPT) during the interictal phase in headache patients, and the relationships between headache frequency and analgesic use. A consecutive series of 98 headache patients and 26 sex- and age-balanced controls were evaluated. Acute allodynia (AA) was assessed by Jakubowski questionnaire, and interictal allodynia (IA) by a skin test with calibrated monofilaments. AA is widely known as a symptom more present in migraine than in TTH spectrum: in our study this was confirmed only in cases of episodic attacks. When headache index rises towards chronicization, the prevalence of AA increases in both headache spectrums (χ2 13.55; p < 0.01). AA was associated with IA only in cases of chronic headache. When headache becomes chronic, mostly in presence of medication overuse, interictal CPT decreases and IA prevalence increases (χ2 20.44; p < 0.01), with closer association than AA. In MOH patients there were no significant differences depending on the diagnosis of starting headache (migraine or tension type headache) and, in both groups, we found the overuse of analgesics plays an important role: intake of more than one daily drug dramatically reduces the CPT (p < 0.05). Thus, when acute allodynia increases frequency, worsens or appears for the first time in patients with a long-standing history of chronic headache, it could reasonably suggest that the reduction of CPT had started, without using a specific practical skin test but simply by questioning clinical headache history. In conclusion, these results indicate that the role of medication overuse is more important than chronicization in lowering CPT, and suggest that prolonged periods of medication overuse can interfere with pain perception by a reduction of the pain threshold that facilitates the onset of every new attack leading to chronicization

Ensemble encoding of nociceptive stimulus intensity in the rat medial and lateral pain systems

<p>Abstract</p> <p>Background</p> <p>The ability to encode noxious stimulus intensity is essential for the neural processing of pain perception. It is well accepted that the intensity information is transmitted within both sensory and affective pathways. However, it remains unclear what the encoding patterns are in the thalamocortical brain regions, and whether the dual pain systems share similar responsibility in intensity coding.</p> <p>Results</p> <p>Multichannel single-unit recordings were used to investigate the activity of individual neurons and neuronal ensembles in the rat brain following the application of noxious laser stimuli of increasing intensity to the hindpaw. Four brain regions were monitored, including two within the lateral sensory pain pathway, namely, the ventral posterior lateral thalamic nuclei and the primary somatosensory cortex, and two in the medial pathway, namely, the medial dorsal thalamic nuclei and the anterior cingulate cortex. Neuron number, firing rate, and ensemble spike count codings were examined in this study. Our results showed that the noxious laser stimulation evoked double-peak responses in all recorded brain regions. Significant correlations were found between the laser intensity and the number of responsive neurons, the firing rates, as well as the mass spike counts (MSCs). MSC coding was generally more efficient than the other two methods. Moreover, the coding capacities of neurons in the two pathways were comparable.</p> <p>Conclusion</p> <p>This study demonstrated the collective contribution of medial and lateral pathway neurons to the noxious intensity coding. Additionally, we provide evidence that ensemble spike count may be the most reliable method for coding pain intensity in the brain.</p

Phantom headache: pain-memory-emotion hypothesis for chronic daily headache?

The neurobiology of chronic pain, including chronic daily headache (CDH) is not completely understood. “Pain memory” hypothesis is one of the mechanisms for phantom limb pain. We reviewed the literature to delineate a relation of “pain memory” for the development of CDH. There is a direct relation of pain to memory. Patients with poor memory have less chance to develop “pain memory”, hence less possibility to develop chronic pain. Progressive memory impairment may lead to decline in headache prevalence. A similar relation of pain is also noted with emotional or psychiatric symptoms. Literature review suggests that there is marked overlap in the neural network of pain to that of memory and emotions. We speculate that pain, memory, and emotions are interrelated in triangular pattern, and each of these three is related to other two in bidirectional pattern, i.e., stimulation of one of these will stimulate other symptoms/networks and vice versa (triangular theory for chronic pain). Longstanding or recurrent noxious stimuli will strengthen this interrelation, and this may be responsible for chronicity of pain. Reduction of both chronic pain and psychological symptoms by cognitive behavioral therapy or psychological interventions further suggests a bidirectional interrelation between pain and emotion. Longitudinal studies are warranted on the prevalence of headache and other painful conditions in patients with progressive memory impairment to delineate the relation of pain to memory. Interrelation of headache to emotional symptoms should also be explored

Moving in an environment of induced sensorimotor incongruence does not influence pain sensitivity in healthy volunteers: A randomised within-subject experiment

Objectives: It has been proposed that in the same way that conflict between vestibular and visual inputs leads to motion sickness, conflict between motor commands and sensory information associated with these commands may contribute to some chronic pain states. Attempts to test this hypothesis by artificially inducing a state of sensorimotor incongruence and assessing self-reported pain have yielded equivocal results. To help clarify the effect sensorimotor incongruence has on pain we investigated the effect of moving in an environment of induced incongruence on pressure pain thresholds (PPT) and the pain experienced immediately on completion of PPT testing. Methods: Thirty-five healthy subjects performed synchronous and asynchronous upper-limb movements with and without mirror visual feedback in random order. We measured PPT over the elbow and the pain evoked by testing. Generalised linear mixed-models were performed for each outcome. Condition (four levels) and baseline values for each outcome were within-subject factors. Results: There was no effect of condition on PPT (p = 0.887) or pressure-evoked pain (p = 0.771). A sensitivity analysis using only the first PPT measure after each condition confirmed the result (p = 0.867). Discussion: Inducing a state of movement related sensorimotor incongruence in the upper-limb of healthy volunteers does not influence PPT, nor the pain evoked by testing. We found no evidence that sensorimotor incongruence upregulates the nociceptive system in healthy volunteer