Line Lindhardt Egsgaard

Abnormal pain processing in chronic tension-type headache: a high-density EEG brain mapping study

Central sensitization caused by prolonged nociceptive input from muscles is considered to play an important role for chronification of tension-type headache. In the present study we used a new high-density EEG brain mapping technique to investigate spatiotemporal aspects of brain activity in response to muscle pain in 19 patients with chronic tension-type headache (CTTH) and 19 healthy, age- and sex-matched controls. Intramuscular electrical stimuli (single and train of five pulses delivered at 2 Hz) were applied to the trapezius muscle and somatosensory evoked potentials were recorded with 128-channel EEG both in- and outside a condition with induced tonic neck/shoulder muscle pain (glutamate injection into the trapezius muscle). Significant reduction in magnitude during and after induced tonic muscle pain was found in controls at the P200 dipole in response to both the first (baseline versus tonic muscle pain: P = 0.001; baseline versus post-tonic muscle pain: P = 0.002) and fifth (baseline versus tonic muscle pain: P = 0.04; baseline versus post-tonic muscle pain: P = 0.04) stimulus in the train. In contrast, there were no differences between the conditions in patients. No consistent difference was found in localization or peak latency of the dipoles. The reduction in magnitude during and after induced tonic muscle pain in controls but not in patients with CTTH may be explained by impaired inhibition of the nociceptive input in these patients. This may be the first evidence that the supraspinal response to muscle pain is abnormal in patients with CTTH.

Association between experimental pain biomarkers and serologic markers in patients with different degrees of painful knee osteoarthritis.

To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain.

A mechanism-based pain sensitivity index to characterize knee osteoarthritis patients with different disease stages and pain levels

In a cohort of well‐characterized patients with different degrees of knee osteoarthritis (OA) and pain, the aims were to utilize mechanism‐based quantitative sensory testing (QST) to (1) characterize subgroups of patients; (2) analyse the associations between clinical characteristics and QST; and (3) develop and apply a QST‐based knee OA composite pain sensitivity index for patient classification.

Identifying specific profiles in patients with different degrees of painful knee osteoarthritis based on serological biochemical and mechanistic pain biomarkers: a diagnostic approach based on cluster analysis

Abstract Biochemical and pain biomarkers can be applied to patients with painful osteoarthritis profiles and may provide more details compared with conventional clinical tools. The aim of this study was to identify an optimal combination of biochemical and pain biomarkers for classification of patients with different degrees of knee pain and joint damage. Such profiling may provide new diagnostic and therapeutic options. A total of 216 patients with different degrees of knee pain (maximal pain during the last 24 hours rated on a visual analog scale [VAS]) (VAS 0-100) and 64 controls (VAS 0-9) were recruited. Patients were separated into 3 groups: VAS 10 to 39 (N = 81), VAS 40 to 69 (N = 70), and VAS 70 to 100 (N = 65). Pressure pain thresholds, temporal summation to pressure stimuli, and conditioning pain modulation were measured from the peripatellar and extrasegmental sites. Biochemical markers indicative for autoinflammation and immunity (VICM, CRP, and CRPM), synovial inflammation (CIIIM), cartilage loss (CIIM), and bone degradation (CIM) were analyzed. WOMAC, Lequesne, and pain catastrophizing scores were collected. Principal component analysis was applied to select the optimal variable subset, and cluster analysis was applied to this subset to create distinctly different knee pain profiles. Four distinct knee pain profiles were identified: profile A (N = 27), profile B (N = 59), profile C (N = 85), and profile D (N = 41). Each knee pain profile had a unique combination of biochemical markers, pain biomarkers, physical impairments, and psychological factors that may provide the basis for mechanism-based diagnosis, individualized treatment, and selection of patients for clinical trials evaluating analgesic compounds. These results introduce a new profiling for knee OA and should be regarded as preliminary.

Automatic determination of synergies by radial basis function artificial neural networks for the control of a neural prosthesis

This paper describes an automatic method for synthesizing the control for a neural prosthesis (NP) that could augment elbow flexion/extension and forearm pronation/supination in persons with hemiplegia. The basis for the control was a synergistic model of reaching and grasping that uses temporal and spatial synergies between the arm and body segments. The synergies were determined from the movement data measured in nondisabled persons during the performance of functional tasks. The work space was divided into six zones: distance (two attributes) and laterality (three attributes). Radial basis function artificial neural networks (RBF ANN) were used to determine synergies. Sets of RBF ANN characterized with good generalization were selected as control laws for elbow flexion/extension and forearm pronation/supination. The validation was performed for three categories: inter-subject, distance, and laterality generalization. For all of the defined spatial synergies, the correlation was high for inter-subject and distance, yet low for the laterality scenario. This suggests the necessity for implementing different maps for different directions, but the same maps for different distances. The natural movements of the upper arm then drive the lower arm (elbow flexion/extension and forearm pronation/supination) in a way that is very well suited for the administration of functional electrical therapy (FET) in persons with hemiplegia soon after the onset of impairment.

Gastrointestinal symptoms in type-1 diabetes: Is it all about brain plasticity?

BACKGROUND AND AIMS Autonomic neuropathy seems to play a central role in the development of gastrointestinal symptoms in diabetes. In order to explore the neuronal mechanisms behind the symptoms we evaluated the brain processing of painful visceral stimuli. METHODS Evoked brain potentials were recorded to assess the response to painful oesophageal electrical stimuli in 15 healthy volunteers and 14 type-1 diabetes patients with autonomic neuropathy and related gastrointestinal symptoms. Source reconstruction analysis (fixed Multiple Signal Classification (MUSIC) algorithm) was applied to estimate the location of the evoked electrical activity in the brain. RESULTS The patients had increased oesophageal sensory thresholds compared to the controls (P=0.004). The latencies of the evoked brain potentials at vertex (Cz) were increased (P=0.007) and amplitudes reduced (P=0.011) in diabetics. Compared with controls the patients had a posterior shift of the electrical sources in the anterior cingulate cortex at 54 ms, and additional sources close to the posterior insula at 95 ms and in medial frontal gyrus at 184 ms. CONCLUSIONS There is evidence of altered central processing to visceral stimulation, and both peripheral and central mechanisms seem involved. Central neuronal reorganisation may contribute to our understanding of the gastrointestinal symptoms in patients with diabetic autonomic neuropathy and this may guide development and evaluation of new treatment modalities.Background and aims: Autonomic neuropathy seems to play a central role in the development of gastrointestinal symptoms in diabetes. In order to explore the neuronal mechanisms behind the symptoms we evaluated the brain processing of painful visceral stimuli.

Central processing of gut pain in diabetic patients with gastrointestinal symptoms.

OBJECTIVE To evaluate the brains responses to painful visceral and somatic stimuli in diabetic patients with gastrointestinal symptoms. RESEARCH DESIGN AND METHODS The sensitivity to electrical esophageal and median nerve stimulations was assessed in 15 healthy volunteers and 14 type 1 diabetic patients with autonomic neuropathy and gastrointestinal symptoms using a euglycemic-hyperinsulinemic clamp. Evoked brain potentials were recorded. RESULTS Patients had reduced sensitivity to esophageal (48%; P < 0.001) and median nerve (80%; P < 0.001) stimulations. They also had increased (8.8%; P = 0.007) and nonreproducible (P = 0.006) latencies of evoked potentials in response to esophageal stimulations, with 26% reduction in amplitude (P = 0.011). No potential differences were seen to median nerve stimulations. In diabetic patients, the topographic location of the first peak in potentials was more central (P < 0.001) and gastrointestinal symptoms correlated with characteristics of brain potentials (P = 0.049). CONCLUSIONS This study supports that diabetes induces changes in peripheral visceral nerves as well as in the central nervous system.

Pain catastrophizing and cortical responses in amputees with varying levels of phantom limb pain: a high-density EEG brain-mapping study

Pain catastrophizing has been associated with phantom limb pain, but so far the cortical processes and the brain regions involved in this relationship have not been investigated. It was therefore tested whether catastrophizing was related to (1) spontaneous pain, (2) somatosensory activity and (3) cortical responses in phantom limb pain patients. The cortical responses were investigated via electroencephalography (EEG) as it has a high temporal resolution which may be ideal for investigating especially the attentional and hypervigilance aspect of catastrophizing to standardized acute stimuli. Eighteen upper limb amputees completed the pain catastrophizing scale. Patients’ spontaneous pain levels (worst and average pain, numerical rating scales) and thresholds to electrical stimulation (sensory detection and VRS2: intense but not painful) were determined. Non-painful electrical stimuli were applied to both the affected and non-affected arm, while high-resolution (128 channels) EEG signals were recorded. Catastrophizing accounted for significant amounts of the variance in relation to spontaneous pain, especially worst pain (64.1%), and it was significantly associated with thresholds. At the affected side, catastrophizing was significantly related to the power RMS of the N/P135 dipole located in the area around the secondary somatosensory cortex which has been shown to be associated with arousal and expectations. These findings corroborate the attentional model of pain catastrophizing by indicating that even non-painful stimuli are related to enhanced attention to and negative expectations of stimuli, and they suggest that memory processes may be central to understanding the link between catastrophizing and pain.

Digital Pain Drawings: Assessing Touch-screen Technology and 3D Body Schemas.

Objectives:To assess the consistency and level of agreement between pain drawings collected on (1) paper and a personal computer tablet; and (2) between a 2-dimensional (2D) line drawing and 3-dimensional (3D) body schema. Materials and Methods:Pain-free participants (N=24) recreated a premarked “pain” area from a 2D line drawing displayed on paper onto paper or tablet, and individuals with chronic neck pain (N=29) expressed their current pain on paper and tablet. A heterogeneous group (N=26) was recruited from cross-disciplinary pain clinic and expressed their pain on a 2D line drawing and a 3D body schema, as displayed on a tablet, and then completed an user-experience questionnaire. Results:Pain drawings showed moderate to high level of consistency and a high level of agreement for paper and tablet and between 2D line drawing and 3D body schema. A fixed bias (−1.0042, P<0.001) revealed that pain areas were drawn slightly smaller on paper than on tablet, and larger on the 2D than the 3D body schema (−0.6371, P=0.003), as recorded on a tablet. Over one-third of individuals with chronic pain preferred and/or believed that the 3D body schema enabled a more accurate record; 12 believed they were equal, and 3 preferred the 2D line drawing. Discussion:Pain drawings recorded with touch-screen technology provide equal reliability to paper but the size of the drawing slightly differs between the platforms. Although, 2D line drawings and 3D body schemas were similar in terms of consistency and reliability, it remains to be confirmed whether 3D body schemas increase the accuracy and precision of pain drawings.

Evidence for a central mode of action for etoricoxib (COX-2 inhibitor) in patients with painful knee osteoarthritis.

Abstract The COX-2 inhibitor etoricoxib modulates the peripheral and central nociceptive mechanisms in animals. This interaction has not been studied in patients with pain. This randomized, double-blind, placebo-controlled, 2-way crossover, 4-week treatment study investigated the pain mechanisms modulated by etoricoxib in patients with painful knee osteoarthritis. Patients were randomized to group A (60 mg/d etoricoxib followed by placebo) or B (placebo followed by 60 mg/d etoricoxib). The quantitative, mechanistic pain biomarkers were pressure pain thresholds, temporal summation (TS), and conditioning pain modulation. Clinical readouts were Brief Pain Inventory, WOMAC, painDETECT questionnaire (PD-Q), and time and pain intensity during walking and stair climbing. Etoricoxib as compared with placebo significantly modulated the pressure pain thresholds (P = 0.012, localized sensitization) at the knee and leg (control site) (P = 0.025, spreading sensitization) and TS assessed from the knee (P = 0.038) and leg (P = 0.045). Conditioning pain modulation was not modulated. The Brief Pain Inventory (pain scores), PD-Q, WOMAC, and walking and stair climbing tests were all significantly improved by etoricoxib. Based on a minimum of 30% or 50% pain alleviation (day 0-day 28), responders and nonresponders were defined. The nonresponders showed a significant association between increased facilitation of TS and increased pain alleviation. None of the other parameters predicted the degree of pain alleviation. Generally, a responder to etoricoxib has the most facilitated TS. In conclusion, etoricoxib (1) modulated central pain modulatory mechanisms and (2) improved pain and function in painful osteoarthritis. Stronger facilitation of TS may indicate a better response to etoricoxib, supporting the central mode-of-action of the drug.