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Patients with chronic pain and especially with craniomandibular disorder (CMD) show specific psychopathology in trait anxiety. In a previous longitudinal functional imaging study on CMD we found that the anterior insula was modulated by successful therapy intervention and pain relief. We here intended to investigate possible associations between anterior insula fMRI-activation during occlusal movements and trait anxiety over a splint therapy approach in patients with CMD. Three fMRI-investigations of a craniomandibular occlusion task were performed together with pain score evaluations and scoring of trait anxiety (State -Trait Anxiety Inventory; STAI) before, after two weeks and after three months of a DIR-mandibular splint therapy in a small group (n = 9) of CMD patients. Patients showed increased anxiety levels before therapy assessed with the STAI and the depression and anxiety scale (DASS). Besides of relevant reduction in pain the STAI decreased over time. Reduction in STAI was associated with anterior insular fMRI-activation reduction on both hemispheres. We conclude that the anxiety driven anticipation of pain related to occlusal trigger is processed in the anterior insula and might therefore be a main driver of therapeutic intervention by the splint therapy in CMD.
Learn More >To study lateral inhibition and habituation/sensitization in the somatosensory cortex of patients with chronic migraine (CM) and to identify correlations with clinical migraine features.
Learn More >Stress and pain have been interrelated in clinical widespread pain conditions. Studies indicate that acute experimental stress in healthy volunteers has a negative effect on the descending inhibitory pain control system and thus the ability to inhibit one painful stimulus with another (conditioned pain modulation [CPM]) although without effect on general pain sensitivity. CPM effects can be assessed immediately after the stress induction, whereas some physiological stress responses (e.g., cortisol release) are delayed and longer lasting. It is unclear whether CPM may relate to stress-induced increases in cortisol.
Learn More >Chronic pain is a debilitating condition of multifactorial origin, often without physical findings to explain the presenting symptoms. Of the possible etiologies of persisting painful symptoms, somatoform disorders and functional somatic syndromes (FSS) are among the most challenging, with a prevalence of 8-20%. Many different somatoform disorders and FSS have overlapping symptoms, with pain being the most prevalent one. The concept of multisomatoform disorder (MSD) has been developed to acknowledge that fact. We hypothesized that the concept of MSD will be reflected in a distinct sensory profile of patients compared with healthy controls and possibly provide insight into the type and pathophysiology of the pain commonly experienced by patients.
Learn More >Older adults experience significant chronic pain after hip fracture, resulting in decreased physical functioning. However, pain investigation in this population is mostly limited to self-reported pain intensity. Detailed pain assessment may identify intervention targets other than pain relief. The aim of this study is to investigate multiple dimensions of pain experience (intensity, sensory, affective, evaluative and miscellaneous dimensions) and to correlate them to lower limb functionality and limitations in daily living activities.
Learn More >ACCURATE, a randomized controlled trial comparing dorsal root ganglion (DRG) stimulation to spinal cord stimulation, showed that DRG stimulation is a safe and effective therapy in individuals with lower extremity chronic pain due to complex regional pain syndrome (CRPS) type I or II. Investigators noted that DRG stimulation programming could be adjusted to minimize, or eliminate, the feeling of paresthesia while maintaining adequate pain relief. The present study explores treatment outcomes for DRG subjects who were paresthesia-free vs. those who experienced the sensation of paresthesia, as well as the factors that predicted paresthesia-free analgesia.
Learn More >We conducted a multicenter, randomized, patient and assessor-blinded, sham-controlled trial to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) in patients with neuropathic pain. Patients were randomly assigned to receive five daily sessions of active or sham rTMS of M1 corresponding to the part of the body experiencing the worst pain (500 pulses per session at 5 Hz). Responders were invited to enroll in an open-label continuous trial involving four weekly sessions of active rTMS. The primary outcome was a mean decrease in a visual analogue scale (VAS) of pain intensity (scaled 0-100 mm) measured daily during the daily sessions in an intention-to-treat population. Secondary outcomes were other pain scores, quality-of-life measures, and depression score. 144 patients were assigned to the active or sham stimulation groups. The primary outcome, mean VAS decreases, was not significantly different (p=0.58) between the active stimulation group (mean, 8.0) and the sham group (9.2) during the daily sessions. The secondary outcomes were not significantly different between two groups. The patients enrolled in the continuous weekly rTMS achieved more pain relief in the active stimulation group compared with the sham (p<0.01). No serious adverse events were observed. Five daily sessions of rTMS with stimulus conditions used in this trial were ineffective in short-term pain relief in the whole study population with various neuropathic pain. Long-term administration to the responders should be investigated for the clinical use of rTMS on neuropathic pain in the future trials.
Learn More >We sought to refine a screening measure for discriminating a sensitized or normal sensation pain phenotype among African American adults with sickle cell disease (SCD).
Learn More >Galcanezumab is a humanized immunoglobulin G (IgG) monoclonal antibody (mAb) indicated for the prevention of migraine that binds to calcitonin gene-related peptide. A population pharmacokinetic (PK) analysis was performed to characterize galcanezumab PK using data pooled from 7 clinical studies. Clinical studies included healthy individuals and patients with episodic or chronic migraine who were administered between 5 and 300 mg galcanezumab. The PK data were analyzed using nonlinear mixed-effects modeling. Galcanezumab concentration-time data were described with a 1-compartment model with first-order absorption following subcutaneous administration and linear elimination. At the median body weight of 74 kg, the estimated population apparent clearance (CL/F) was 0.00785 L/h (34% IIV), the apparent volume of distribution was 7.33 L (34% IIV), and half-life was 27 days. Patient body weight was found to have a modest effect of CL/F, with median galcanezumab concentrations being lower in the heaviest patients compared to the lightest patients, but this outcome was determined not to be clinically relevant in the context of model-estimated random variability. Dosing adjusted for body weight is not warranted in adults. Age, sex, race/ethnicity, immunogenicity, renal/hepatic markers, and injection-site location did not affect galcanezumab PK. In conclusion, galcanezumab exhibits PK parameters typical for an IgG mAb administered subcutaneously. The population PK model developed in this study demonstrates that galcanezumab exhibits linear PK that was not influenced in a clinically relevant manner by the patient factors evaluated.
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