0000000000009346
AUTHOR
Markus Breimhorst
Pain in chemotherapy-induced neuropathy – More than neuropathic?
Chemotherapy-induced neuropathy (CIN) is an adverse effect of chemotherapy. Pain in CIN might comprise neuropathic and nonneuropathic (ie, musculoskeletal) pain components, which might be characterized by pain patterns, electrophysiology, and somatosensory profiling. Included were 146 patients (100 female, 46 male; aged 56 ± 0.8 years) with CIN arising from different chemotherapy regimens. Patients were characterized clinically through nerve conduction studies (NCS) and quantitative sensory testing (QST). Questionnaires for pain (McGill) and anxiety/depression (Hospital Anxiety and Depression Scale) were supplied. Patients were followed-up after 17 days. Large- (61%) and mixed- (35%) fibre …
Detection of central circuits implicated in the formation of novel pain memories
Jaymin Upadhyay,1 Julia Granitzka,1 Thomas Bauermann,2 Ulf Baumgärtner,3 Markus Breimhorst,1 Rolf-Detlef Treede,3 Frank Birklein1 1Department of Neurology, 2Department of Neuroradiology, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, 3Department of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim (CBTM), Heidelberg University, Mannheim, Germany Abstract: Being able to remember physically and emotionally painful events in one’s own past may shape behavior, and can create an aversion to a variety of situations. Pain imagination is a related process that may include recall of past experiences, in addition to production of sensor…
Meta-analysis of real-time fMRI neurofeedback studies using individual participant data: How is brain regulation mediated?
An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different ta…
Stress and thermoregulation: different sympathetic responses and different effects on experimental pain.
Stress and thermoregulation both activate the sympathetic nervous system (SNS) but might differently affect pain. Studies investigating possible interactions in patients are problematic because of the high prevalence of SNS disturbances in patients. We therefore analyzed the influence of these different sympathetic challenges on experimentally-induced pain in healthy subjects. SNS was activated in two different ways: by mental stress (Stroop task, mental arithmetic task), and by thermoregulatory stimulation using a water-perfused thermal suit (7 degrees C, 32 degrees C, or 50 degrees C). Attentional effects of the mental stress tasks were controlled by using easy control tasks. Both, stress…
Within-session sensitization and between-session habituation: A robust physiological response to repetitive painful heat stimulation
Habituation and sensitization are important behavioural responses to repeated exposure of painful stimuli. Whereas within-session response dynamics to nociceptive stimuli is well characterized, little is known about long-term behaviour due to repetitive nociceptive stimulation. We used a standardized longitudinal heat pain paradigm in 66 healthy participants, 21 patients with chronic low back pain and 22 patients with depression who received daily sessions of 60 suprathreshold heat stimuli (48 °C each) for eight consecutive days. All three groups showed the same response: Repeated painful stimulation over several days resulted in substantially decreased pain ratings to identical painful sti…
Naloxone inhibits not only stress-induced analgesia but also sympathetic activation and baroreceptor-reflex sensitivity
Interactions between the sympathetic nervous system and pain are manifold and still have not been sufficiently characterized. Accordingly, several possible neuronal pathways have been described as being involved in mental stress-induced analgesia. We studied the role of the endogenous opioidergic system in stress-induced analgesia in 14 healthy participants in a double-blind cross-over trial. Naloxone or placebo was applied while electrical pain stimulation was started and electrical current increased. After reaching a constant stimulation at 30 mA, a color word interference test (Stroop task) was performed in a stressful and a non-stressful version. Blood pressure, heart rate and barorefle…
Comparison of anterior cingulate vs. insular cortex as targets for real-time fMRI regulation during pain stimulation
© 2014 Emmert Breimhorst Bauermann Birklein Van De Ville and Haller. Real time functional magnetic resonance imaging (rt fMRI) neurofeedback allows learning voluntary control over specific brain areas by means of operant conditioning and has been shown to decrease pain perception. To further increase the effect of rt fMRI neurofeedback on pain we directly compared two different target regions of the pain network notably the anterior insular cortex (AIC) and the anterior cingulate cortex (ACC). Participants for this prospective study were randomly assigned to two age matched groups of 14 participants each (7 females per group) for AIC and ACC feedback. First a functional localizer using bloc…
Association between pain, central sensitization and anxiety in postherpetic neuralgia
Background In postherpetic neuralgia (PHN), dorsal root ganglia neurons are damaged. According to the proposed models, PHN pain might be associated with nociceptive deafferentation, and peripheral (heat hyperalgesia) or central sensitization (allodynia). Methods In 36 PHN patients, afferent nerve fibre function was characterized using quantitative sensory testing and histamine-induced flare analysis. Psychological factors were evaluated with the Hospital Anxiety and Depression Scale (HADS), disease-related quality of life (QoL) with SF-36 and pain with the McGill questionnaire [pain rating index (PRI)]. The patients were also divided into subgroups according to the presence or absence of br…
Inhibition of neuropeptide degradation suppresses sweating but increases the area of the axon reflex flare.
The neuropeptides CGRP (calcitonin gene-elated peptide) and substance P (SP) mediate neurogenic inflammation. Both are degraded by the neutral endopeptidase (NEP) which can be blocked by phosphoramidon. The aim was to evaluate the effect of NEP inhibition on sweating and vasodilatation. Dermal microdialysis was performed on the skin of 39 subjects. Two fibres were perfused with phosphoramidon (0.01%, 0.02% or 0.2%), two with saline. Acetylcholine (ACh) was either added to the microdialysis perfusate (n = 30, 10(-2) m) or thermoregulatory sweating was induced (n = 9). Co-application of phosphoramidon reduced cholinergic and thermoregulatory sweating. However, the flare size - a localized in…
Latency of interictal epileptiform discharges in long-term EEG recordings in epilepsy patients.
AbstractPurposeTo assess the latency of interictal epileptiform discharges (IED) and seizures in long-term EEG recordings of patients with epilepsy.MethodIED latency was measured in 210 consecutive patients (mean (SD) age 38.6±13.9 years) with active epilepsy and the relationship to clinical variables was analyzed retrospectively. Median duration of EEG recording was 101.5h (95% confidence interval [CI] 92 to 117h).ResultsIEDs were absent in 45 (21.4%) and present in 165 (78.6%) patients who had a longer duration (p<0.001) and early onset (p<0.01) of epilepsy and more often had IEDs in prior standard EEGs (p<0.01), a structural etiology (OR 2.4, CI: 2.1–2.7), or temporal lobe epilepsy (OR 9…
The efficacy of acupuncture in human pain models: A randomized, controlled, double-blinded study
Acupuncture is frequently used to treat pain, although data supporting the analgesic efficacy from placebo-controlled studies is sparse. In order to get evidence for acupuncture analgesia we performed a study with 2 well-recognized experimental human pain models - the cold-pressor (CP) test and intradermal capsaicin injection. Fifty healthy men were included. Our study compared Traditional Chinese Medicine-based acupuncture to sham acupuncture with Streitberger placebo needles in a randomized, controlled, double-blinded trial. The primary endpoint was the reduction of mean pain intensity during 3minutes of CP test or of mean pain intensity within 10minutes after capsaicin injection. Seconda…
Functional imaging of sympathetic activation during mental stress
Activation of the sympathetic nervous system (SNS) is essential in adapting to environmental stressors and in maintaining homeostasis. This reaction can also turn into maladaptation, associated with a wide spectrum of stress-related diseases. Up to now, the cortical mechanisms of sympathetic activation in acute mental stress have not been sufficiently characterized. We therefore investigated cerebral activation applying functional magnetic resonance imaging (fMRI) during performance of a mental stress task with graded levels of difficulty, i.e. four versions of a Stroop task (Colour Word Interference Test, CWT) in healthy subjects. To analyze stress-associated sympathetic activation, skin c…
Osteoprotegerin: a new biomarker for impaired bone metabolism in complex regional pain syndrome?
Abstract Osteoprotegerin (OPG) is important for bone remodeling and may contribute to complex regional pain syndrome (CRPS) pathophysiology. We aimed to assess the value of OPG as a biomarker for CRPS and a possible correlation with radiotracer uptake in 3-phase bone scintigraphy (TPBS). OPG levels were analyzed in 23 CRPS patients (17 women; mean age 50 ± 9.0 years; disease duration: 12 weeks [IQR 8–24]), 10 controls (6 women; mean age 58 ± 9.6 years) and 21 patients after uncomplicated fractures (12 women; mean age: 43 ± 15 years; time after fracture: 15 weeks [IQR: 6–22]). The CRPS and control patients also underwent TPBS. OPG in CRPS patients was significantly increased by comparison wi…
Central correlation of muscle sympathetic nerve activation during baroreflex unloading - a microneurography-positron emission tomography study
The baroreceptor reflex controls spontaneous fluctuations in blood pressure. One major control variable of the baroreflex is the sympathetic vasoconstrictor activity to muscles [MSNA; burst frequency (BF) and burst incidence (BI)], which can be quantitatively assessed by microneurography. We aimed to investigate the central regions involved in baroreflex regulation of MSNA. Healthy men (mean age 25 years) participated in three experimental sessions. (i) Microneurography recordings of MSNA from the left peroneal nerve during rest and baroreflex unloading, induced by lower body negative pressure (LBNP; -40 mmHg). If MSNA could be reliably recorded throughout this procedure (n = 15), the subje…
Expectations modulate long-term heat pain habituation.
Habituation to pain was shown to be a complex mechanism involving the pain encoding regions and the antinociceptive system in the brain. Pain perception can be modulated by cognitive factors; however it is unclear whether cognitive factors also influence habituation to pain. We used an established experimental design with repetitive moderate painful heat stimulation over eight consecutive days. Thirty-seven healthy subjects were recruited and assigned to four different groups: The first group (n=10) was instructed that pain perception over time will habituate; the second group (n=9) that pain will increase; the third group (n=8) was instructed that pain will remain stable over the 8 days of…
Differential effect of Incobotulinumtoxin A on pain, neurogenic flare and hyperalgesia in human surrogate models of neurogenic pain
Background: The effectiveness of Botulinum-neurotoxin A (BoNT/A) to treat pain in human pain models is very divergent. This study was conducted to clarify if the pain models or the route of BoNT/A application might be responsible for these divergent findings. Methods: Sixteen healthy subjects (8 males, mean age 27 ± 5 years) were included in a first set of experiments consisting of three visits: (1) Visit: Quantitative sensory testing (QST) was performed before and after intradermal capsaicin injection (CAPS, 15 μg) on one thigh and electrical current stimulation (ES, 1 Hz) on the contralateral thigh. During stimulation pain and the neurogenic flare response (laser-Doppler imaging) were ass…
Sensory and sympathetic correlates of heat pain sensitization and habituation in men and women
Background Habituation and sensitization are important behavioural responses to repeated exposure to painful stimuli, but little is known about the factors determining sensory, affective and sympathetic habituation to repeated pain stimulation in men and women. Methods Thirty volunteers (15 women) underwent a standardized heat pain paradigm spread over 8 consecutive days. At the beginning of the experiment, personality dimensions, coping strategies and pain catastrophizing thoughts were determined. Receiving a series of 10 blocks of six painful heat stimuli a day, participants rated pain intensity and unpleasantness. Skin conductance was recorded throughout the sessions. Results and Conclus…
Mental load during cognitive performance in complex regional pain syndrome I.
Background Complex regional pain syndrome (CRPS) is associated with deficits in limb recognition. The purpose of our study was to determine whether mental load during this task affected performance, sympathetic nervous system activity or pain in CRPS patients. Methods We investigated twenty CRPS‐I patients with pain in the upper extremity and twenty age‐ and sex‐matched healthy controls. Each participant completed a limb recognition task. To experimentally manipulate mental load, the presentation time for each picture varied from 2 s (greatest mental load), 4, 6 to 10 s (least mental load). Before and after each run, pain intensity was assessed. Skin conductance was recorded continuously. R…
Do Intensity Ratings and Skin Conductance Responses Reliably Discriminate Between Different Stimulus Intensities in Experimentally Induced Pain?
Abstract The present study addresses the question whether pain-intensity ratings and skin conductance responses (SCRs) are able to detect different intensities of phasic painful stimuli and to determine the reliability of this discrimination. For this purpose, 42 healthy participants of both genders were assigned to either electrical, mechanical, or laser heat-pain stimulation (each n = 14). A whole range of single brief painful stimuli were delivered on the right volar forearm of the dominant hand in a randomized order. Pain-intensity ratings and SCRs were analyzed. Using generalizability theory, individual and gender differences were the main contributors to the variability of both intens…