Anne-Kathrin Bräscher

Different Brain Circuitries Mediating Controllable and Uncontrollable Pain

Uncontrollable, compared with controllable, painful stimulation can lead to increased pain perception and activation in pain-processing brain regions, but it is currently unknown which brain areas mediate this effect. When pain is controllable, the lateral prefrontal cortex (PFC) seems to inhibit pain processing, although it is unclear how this is achieved. Using fMRI in healthy volunteers, we examined brain activation during controllable and uncontrollable stimulation to answer these questions. In the controllable task, participants self-adjusted temperatures applied to their hand of pain or warm intensities to provoke a constant sensation. In the uncontrollable task, the temperature time courses of the controllable task were replayed (yoked control) and participants rated their sensation continuously. During controllable pain trials, participants significantly downregulated the temperature to keep their sensation constant. Despite receiving the identical nociceptive input, intensity ratings increased during the uncontrollable pain trials. This additional sensitization was mirrored in increased activation of pain-processing regions such as insula, anterior cingulate cortex, and thalamus. Further, increased connectivity between the anterior insula and medial PFC (mPFC) in the uncontrollable and increased negative connectivity between dorsolateral PFC (dlPFC) and insula in the controllable task were observed. This suggests a pain-facilitating role of the mPFC during uncontrollable pain and a pain-inhibiting role of the dlPFC during controllable pain, both exerting their respective effects via the anterior insula. These results elucidate neural mechanisms of context-dependent pain modulation and their relation to subjective perception. SIGNIFICANCE STATEMENT Pain control is of uttermost importance and stimulus controllability is an important way to achieve endogenous pain modulation. Here, we show differential effects of controllability and uncontrollability on pain perception and cerebral pain processing. When pain was controllable, the dorsolateral prefrontal cortex downregulated pain-evoked activation in important pain-processing regions. In contrast, sensitization during uncontrollable pain was mediated by increased connectivity of the medial prefrontal cortex with the anterior insula and other pain-processing regions. These novel insights into cerebral pain modulation by stimulus controllability have the potential to improve treatment approaches in pain patients.

Are media reports able to cause somatic symptoms attributed to WiFi radiation? An experimental test of the negative expectation hypothesis

ABSTRACT People suffering from idiopathic environmental intolerance attributed to electromagnetic fields (IEI‐EMF) experience numerous non‐specific symptoms that they attribute to EMF. The cause of this condition remains vague and evidence shows that psychological rather than bioelectromagnetic mechanisms are at work. We hypothesized a role of media reports in the etiology of IEI‐EMF and investigated how somatosensory perception is affected. 65 healthy participants were instructed that EMF exposure can lead to enhanced somatosensory perception. Participants were randomly assigned to watch either a television report on adverse health effects of EMF or a neutral report. During the following experiment, participants rated stimulus intensities of tactile (electric) stimuli while being exposed to a sham WiFi signal in 50% of the trials. Sham WiFi exposure led to increased intensity ratings of tactile stimuli in the WiFi film group, especially in participants with higher levels of somatosensory amplification. Participants of the WiFi group reported more anxiety concerning WiFi exposure than the Control group and tended to perceive themselves as being more sensitive to EMF after the experiment compared to before. Sensational media reports can facilitate enhanced perception of tactile stimuli in healthy participants. People tending to perceive bodily symptoms as intense, disturbing, and noxious seem most vulnerable. Receiving sensational media reports might sensitize people to develop a nocebo effect and thereby contribute to the development of IEI‐EMF. By promoting catastrophizing thoughts and increasing symptom‐focused attention, perception might more readily be enhanced and misattributed to EMF. HighlightsThe etiology of idiopathic environmental intolerance attributed to electromagnetic fields (IEI‐EMF) is unknown.Expectations induced by sensational TV reports could be important in this context.Watching a sensational movie on EM radiation enhances tactile sensitivity.Especially vulnerable are persons with high levels of somatosensory amplification.IEI‐EMF might be caused by a nocebo effect.

Ultrasound-Guided Stellate Ganglion Blocks Combined with Pharmacological and Occupational Therapy in Complex Regional Pain Syndrome (CRPS): A Pilot Case Series Ad Interim

OBJECTIVE This preliminary and retrospective pilot case series examines a treatment concept consisting of ultrasound-guided stellate ganglion blocks (SGBs) combined with pharmacological and occupational therapy in patients with complex regional pain syndrome (CRPS) of the hand. Efficacy of combined treatment concepts and safety of ultrasound-guided SGB have not been sufficiently investigated yet. METHODS A total number of 156 blocks were evaluated in 16 patients with CRPS in a retrospective analysis. All patients received pharmacotherapy and a standard regimen of occupational therapy offered simultaneously to the SGBs. Changes in both spontaneous and evoked pain levels were assessed by numerical pain rating score before and after the last blockade of a series. Side effects were documented. RESULTS The overall mean pain reduction was 63.2% regarding spontaneous and 45.3% regarding evoked pain. Mild complications, such as hoarseness or dysphagia, occurred in 13.5% of the blocks (21 SGBs). Serious complications, such as plexus paresis or accidental puncture of vessels or other structures, did not occur. Time between symptom onset and start of treatment did not affect the extent of pain reduction. CONCLUSIONS The combination of ultrasound-guided SGB and simultaneous pharmacological and occupational therapy showed encouraging treatment results under conditions of this pilot case series. Assessment of efficacy of this combined treatment concept and safety of ultrasound-guided SGB require further prospective clinical studies with larger number of participants.

Comprehensive Curriculum for Phantom-Based Training of Ultrasound-Guided Intercostal Nerve and Stellate Ganglion Blocks

OBJECTIVE Ultrasound (US)-guided pain procedures become increasingly important due to their numerous advantages. Solid proficiency is necessary, however, to minimize complications and guarantee adequate performance. To enable beginners to learn the relevant skills in the technique of US-guided stellate ganglion (SGB) and intercostal nerve block (ICB), a training curriculum was developed and tested using self-made phantoms. DESIGN The curriculum comprised an introduction to the didactics of US, SGB, and ICB, a demonstration of the techniques by an expert user, as well as hands-on training of needle guidance using a gel pad and two phantoms. SUBJECTS Three groups of participants with different levels of expertise with US-guided procedures took part in the curriculum: 12 medical students with no prior experience, 12 anesthesiologists with some experience, and five senior anesthesiologists who already applied these techniques on a regular basis. METHODS Participants evaluated the curriculum via questionnaire, and their performance of time until adequate puncture, attempts required for adequate puncture, number of corrections, and unintentional punctures was assessed. RESULTS The medical students significantly increased their speed during both nerve blocks and reduced the number of attempts and corrections necessary to perform adequate ICB. The anesthesiologists with some experience also increased their speed in both blocks. The participants rated the curriculum as good to very good. CONCLUSIONS The combination of theoretical teaching, expert demonstration, and hands-on training on phantoms proved useful in acquiring skills needed for US-guided procedures such as SGB and ICB, and can potentially improve graduate and post-graduate medical education.

Improvements in health-related quality of life by comprehensive cancer pain therapy: a pilot study with breast cancer outpatients under palliative chemotherapy.

Background: Cancer-related pain is highly prevalent among outpatients with metastatic breast cancer affecting their health-related quality of life (HRQoL). This study evaluates potential effects of comprehensive pharmacologic cancer pain therapy (CPT) on HRQoL. Patients and Methods: 52 outpatients with metastatic breast cancer undergoing palliative chemotherapy participated. 28 patients suffering from moderate to severe cancer pain were offered CPT. 13 patients participated (intervention group), and 15 declined participation (control group). HRQoL was assessed with the Quality of Life Questionnaire (EORTC QLQ-C30) and the breast module QLQ-BR23 at baseline and after 3 weeks. Results: At baseline, 83% of the patients experienced cancer-related pain, of whom 35% were not prescribed any pain medication. HRQoL of all patients was reduced compared to reference scores. After CPT, the intervention group reported significantly alleviated pain and improvement in several HRQoL subscales (Global QoL, Emotional Functioning, Physical Functioning, Future Perspective, Sleeplessness). The control group did not change significantly. Conclusion: This study emphasizes the demand for sufficient pain management in palliative breast cancer outpatients. The combination of CPT as a guidance for the pharmacological aspects of cancer pain management and the EORTC QLQ-C30 as an assessment and surveillance tool appears to be a method that warrants further research.

On the origin of worries about modern health hazards: Experimental evidence for a conjoint influence of media reports and personality traits

Objective: Worries about health threatening effects of potential health hazards of modern life (e.g. electric devices and pollution) represent a growing phenomenon in Western countries. Yet, little is known about the causes of this growing special case of affective risk perceptions termed Modern Health Worries (MHW). The purpose of this study is to examine a possible role of biased media reports in the formation of MHW. Design: In two experiments, we investigated whether typical television reports affect MHW. In Study 1, 130 participants were randomly assigned to a film on idiopathic environmental intolerance (IEI) or a control film about cystic fibrosis. In Study 2, 82 participants were randomly assigned to either a film on the dangers of electromagnetic fields or a control condition. Main outcome measures: Increases in MHW after sensational media reports. Results: In Study 1, only participants high on the personality trait of absorption revealed increased MHW after watching the IEI film. In Study 2, specifically worries about radiation were found to be elevated after watching the film on the dangers of electromagnetic fields compared to the control film. Conclusion: The results of both studies reveal a significant and specific influence of sensational short mass media reports on MHW. The influence of potential moderators such as absorption remains to be clarified.

The Underestimated Significance of Conditioning in Placebo Hypoalgesia and Nocebo Hyperalgesia

Placebo and nocebo effects are intriguing phenomena in pain perception with important implications for clinical research and practice because they can alleviate or increase pain. According to current theoretical accounts, these effects can be shaped by verbal suggestions, social observational learning, and classical conditioning and are necessarily mediated by explicit expectation. In this review, we focus on the contribution of conditioning in the induction of placebo hypoalgesia and nocebo hyperalgesia and present accumulating evidence that conditioning independent from explicit expectation can cause these effects. Especially studies using subliminal stimulus presentation and implicit conditioning (i.e., without contingency awareness) that bypass the development of explicit expectation suggest that conditioning without explicit expectation can lead to placebo and nocebo effects in pain perception. Because only few studies have investigated clinical samples, the picture seems less clear when it comes to patient populations with chronic pain. However, conditioning appears to be a promising means to optimize treatment. In order to get a better insight into the mechanisms of placebo and nocebo effects in pain and the possible benefits of conditioning compared to explicit expectation, future studies should carefully distinguish both methods of induction.

Differential Classical Conditioning of the Nocebo Effect: Increasing Heat-Pain Perception without Verbal Suggestions

Background: Nocebo effects, including nocebo hyperalgesia, are a common phenomenon in clinical routine with manifold negative consequences. Both explicit expectations and learning by conditioning are known to induce nocebo effects, but the specific role of conditioning remains unclear, because conditioning is rarely implemented independent of verbal suggestions. Further, although pain is a multidimensional phenomenon, nocebo effects are usually assessed in subjective ratings only, neglecting, e.g., behavioral aspects. The aim of this study was to test whether nocebo hyperalgesia can be learned by conditioning without explicit expectations, to assess nocebo effects in different response channels, and to exploratively assess, whether contingency awareness is a necessary condition for conditioned nocebo hyperalgesia. Methods: Twenty-one healthy volunteers were classically conditioned using painful and non-painful heat stimuli that followed two different cues. The conditioned nocebo effect was assessed by subjective ratings of perceived stimulation intensity on a visual analog scale and a behavioral discrimination task, assessing sensitization and habituation in response to the same stimulation following the two cues. Results: Results show a conditioned nocebo effect indicated by the subjective intensity ratings. Conditioned effects were also seen in the behavioral responses, but paradoxically, behavioral responses indicated decreased perception after conditioning, but only for subjects successfully conditioned as indicated by the subjective ratings. Explorative analyses suggested that awareness of the contingencies and the different cues was not necessary for successful conditioning. Conclusion: Nocebo effects can be learned without inducing additional explicit expectations. The dissociation between the two response channels, possibly representing the conditioned and a compensatory response, highlights the importance of considering different outcomes in nocebo responses to fully understand underlying mechanisms. The present results challenge the role of explicit expectations in conditioned nocebo effects and are relevant with implications in clinical contexts, e.g., when transient adverse effects become conditioned.

Interventional pain therapy. Results of a survey among specialized pain physicians in Germany

BACKGROUND Interventional pain therapy aims to treat pain which is refractory to pharmacologic and noninterventional treatment. Due to the partly lacking evidence and recommendations it remains unclear when interventional methods should be applied within the treatment pathway. This study assesses the current state of interventional methods in Germany and their leading indications comparing with the recommendations found in the literature. METHODS An online survey was conducted among German physicians specialized in pain therapy concerning the number of interventions they perform per quarter, which supporting measures they use, and their indications for sympathetic blocks, sensory blocks, intrathecal administration, and spinal cord stimulation. RESULTS A total of 109 physicians (23.5 %) participated in the survey. Blocks are most often performed on the stellate ganglion (94 %) and on the superior cervical ganglion (82 %). They are supported by anatomical landmarks and less often by imaging control. Both classic neuropathic pain diagnoses (e.g., complex regional pain syndrome) and diagnoses with a neuropathic pain component (e.g., peripheral arterial disease, tumor pain, and back pain) were considered as indications to perform interventional procedures. CONCLUSION Although there is no clear evidence on interventional procedures in the current literature, these methods are often performed by the respondents. Anatomic landmarks are most frequently used for orientation. The German pain physicians who responded consider especially neuropathic pain as an indication to perform interventional procedures for pain therapy.

Medical educational evaluation of the German Pain Congress 2012. In the context of the CanMEDS physician competency framework

BACKGROUND Professionals in the medical field are expected to participate in continuing medical education in the sense of lifelong learning. The authors took this occasion to evaluate the most important national convention in pain medicine concerning its role in medical education. MATERIAL AND METHODS The participants of the 37th German Pain Congress (17-20 October 2012 in Mannheim) were asked to complete a questionnaire concerning content and design of the convention. The aim of this study was to analyze the distribution of different physician competencies in the program. For this purpose the congress program was analyzed with respect to the various medical role models as defined in the Canadian medical education directions for specialists (CanMEDS) framework. RESULTS The participants considered the quality of the different sessions of the German Pain Congress to be good. The poster sessions were considered to be the second most important educational format in the congress following the live sessions. Concerning the content of the congress the participants wished more emphasis on the role of interprofessional partners, such as nursing and psychotherapy. The CanMEDS physician roles of manager, communicator, health advisor and professional paragon were underrepresented in the congress program in this study. CONCLUSION Regarding content and educational value, the congress design could benefit from additional Praktikerseminaren (practical seminars). The role of interprofessional partners should be more emphasized. In addition the program could become more attractive through a more balanced distribution of the CanMEDS roles.