[Booster treatments in interdisciplinary multimodal pain therapy : Preparing structural and process parameters for the implementation of cross-sectoral booster treatments]. / Boosterbehandlungen in der interdisziplinären multimodalen Schmerztherapie : Vorbereitung von Struktur- und Prozessparametern zur Umsetzung von sektorenübergreifenden Boosterbehandlungen.

Interdisciplinary multimodal pain therapy (IMPT) is an established procedure in the treatment of chronic pain. In daily practice, many institutions regard so-called booster units as an integral part of IMPT. However, no consensual recommendations and evidence for booster concepts are available to date. This article uses the results of a discussion between clinical experts in the field of IMPT at the German Pain Congress in 2022 in order to show the status quo in care. It has been shown that currently applied booster offers vary greatly in terms of time intervals, intensities, therapy content and patient selection and that there is a need for structural and process parameters for the implementation of cross-sectoral booster treatments. In conclusion, the authors outline how the development of these parameters will be planned as an expert consensus with the participation of interested institutions and the inclusion of the patient perspective and offer opportunities for participation in this process.

Safety and efficacy of prednisone versus placebo in short-term prevention of episodic cluster headache: a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Prednisone is commonly used for initial short-term therapy of episodic cluster headaches before preventive medication such as verapamil becomes effective, but this strategy has not been tested in large randomised trials. We aimed to access the safety and efficacy of this treatment approach. METHODS: This study was a multicentre, randomised, double-blind, placebo-controlled trial done in ten specialised headache centres in Germany. Patients with episodic cluster headaches who were aged between 18 and 65 years and within a current pain episode for not more than 30 days, received 100 mg oral prednisone for 5 days followed by tapering of 20 mg every 3 days, or matching placebo (17 days total exposure). All patients received oral verapamil for long-term prevention, starting with 40 mg three times daily and increasing to 120 mg three times daily by day 19; patients then continued with verapamil 120 mg throughout the study. Randomisation was computer-generated at a 1:1 ratio by use of an interactive web-response system, with stratification according to age, sex, and participating site. Participants, investigators, and those assessing outcomes were unaware of treatment allocation. The primary endpoint was the mean number of attacks within the first week of treatment with prednisone compared with placebo. An attack was defined as a unilateral headache with moderate-to-severe intensity of at least five on a numerical rating scale. All efficacy and safety analyses were done in the modified intention-to-treat (mITT) population, which consisted of all patients who had been randomly assigned to a trial group and received at least one dose of prednisone or placebo. The study was stopped early due to slow recruitment and expired funding. The study was registered with EudraCT (2011-006204-13) and with the German Clinical Trials Register (DRKS00004716). FINDINGS: Between April 5, 2013, and Jan 11, 2018, 118 patients were enrolled in the study. Two patients dropped out immediately and 116 patients were randomly assigned (57 patients to prednisone and 59 patients to placebo); 109 patients were included in the mITT analysis (53 patients assigned to prednisone and 56 patients assigned to placebo). Participants in the prednisone group had a mean of 7·1 (SD 6·5) attacks within the first week compared with 9·5 (6·0) attacks in the placebo group (difference -2·4 attacks, 95% CI -4·8 to -0·03; p=0·002). Two serious adverse events occurred, both in the placebo group (inguinal hernia and severe deterioration of cluster headache). A total of 270 adverse events were observed: in the prednisone group, 37 (71%) of 52 patients reported 135 adverse events (most common were headache, palpitations, dizziness, and nausea) and in the placebo group, 39 (71%) of 55 patients had 135 adverse events (most common were nausea, dizziness, and headache). INTERPRETATION: Oral prednisone was an effective short-term preventive therapy in our population of patients with episodic cluster headache. Our findings support the use of prednisone as a first-line treatment in parallel to the up-titration of verapamil, although the efficacy of prednisone alongside other long-term prevention requires additional investigation. FUNDING: German Federal Ministry for Education and Research.

How does reduction in pain lead to reduction in disability in patients with musculoskeletal pain?

PURPOSE: Reduction in pain following multidisciplinary treatment is most often associated with a reduction in disability. To further elaborate the relationship between pain intensity and disability, the present study investigated three main questions: first, whether multidisciplinary treatment leads to a significant improvement in pain, disability and psychological variables (depression, pain acceptance and catastrophizing). Second, it was examined whether pain reduction may account for significant changes in the psychological variables (pre- to follow-up change scores). Finally, it was analyzed whether the psychological changes mediate the association between reduction in pain and in disability after controlling for age, sex and pain history. PATIENTS AND METHODS: Patients suffering from chronic musculoskeletal pain (n=279) attended a German inpatient multidisciplinary program lasting 15 consecutive days on average, with self-report data collected at pretreatment, posttreatment and three-month follow-up. RESULTS: Repeated measures ANOVAs showed a significant improvement in pain intensity, disability, pain acceptance, catastrophizing and depression at posttreatment and follow-up. Univariate regression analyses revealed that changes in pain intensity accounted for significant changes in depression, pain catastrophizing and pain acceptance (pre- to follow-up change scores). The results of Multiple Mediation Procedure showed that pain reduction did affect reduction in disability through improvement of depression, catastrophizing and acceptance. CONCLUSION: Our findings support a cognitive-behavioral model of pain that posits an important role for pain-related cognitive and emotional processes in long-term outcomes following multidisciplinary pain treatment, in particular for the modulation of disability due to pain. The results add evidence to the notion that pain-related cognitions are dynamic features varying over time dependent on the internal situation. PERSPECTIVE: The current findings are relevant to the management of patients with musculoskeletal pain. The results support the notion that, in contrast with the view of enduring personality traits, pain-related cognitions and emotions reflect a situational response that varies over time.

Predicting factors of outcome in multidisciplinary treatment of chronic neuropathic pain.

PURPOSE: Evidence of the effectiveness of multidisciplinary treatment with a focus on neuropathic pain is still rare. The present study investigated whether multidisciplinary treatment leads to improvement of neuropathic pain in outcome (pain intensity and disability) and psychological (depression, pain acceptance, and catastrophizing) variables at posttreatment and 3-month follow-up. We examined whether and to what extent psychological changes can predict long-term outcome at 3-month follow-up, when other variables are controlled for (baseline characteristics and changes in pain parameters). PATIENTS AND METHODS: Patients suffering from a chronic neuropathic pain condition (n=141) attended an inpatient multidisciplinary program lasting about 15 continuous days with self-report data collected at pretreatment, posttreatment, and 3-month follow-up. RESULTS: Repeated-measures ANOVAs showed a significant improvement of pain intensity, disability, pain acceptance, catastrophizing, and depression at posttreatment. These improvements remained stable over the 3-month follow-up for all variables except for depression. The inclusion of psychological changes in multiple regression analyses greatly increased the variance in outcome, explained by baseline characteristics and changes in pain parameters. CONCLUSION: The results could help clinicians to determine which variables should be emphasized during inpatient treatment and during the follow-up period, in order to maintain the gains after an inpatient multidisciplinary treatment for neuropathic pain. PERSPECTIVE: The present study demonstrates the beneficial effects of an inpatient multidisciplinary program for neuropathic pain and further question the resistant nature of neuropathic pain to treatment. The results add evidence to the relevance of cognitive-behavioral models of pain positing an important role for pain-related thoughts and emotions in long-term outcome following multidisciplinary pain treatment.

Improved surgical procedure using intraoperative navigation for the implantation of the SPG microstimulator in patients with chronic cluster headache.

INTRODUCTION: The ATI SPG microstimulator is designed to be fixed on the posterior maxilla, with the integrated lead extending into the pterygopalatine fossa to electrically stimulate the sphenopalatine ganglion (SPG) as a treatment for cluster headache. Preoperative surgical planning to ensure the placement of the microstimulator in close proximity (within 5 mm) to the SPG is critical for treatment efficacy. The aim of this study was to improve the surgical procedure by navigating the initial dissection prior to implantation using a passive optical navigation system and to match the post-operative CBCT images with the preoperative treatment plan to verify the accuracy of the intraoperative placement of the microstimulator. METHODS: Custom methods and software were used that result in a 3D rotatable digitally reconstructed fluoroscopic image illustrating the patient-specific placement with the ATI SPG microstimulator. Those software tools were preoperatively integrated with the planning software of the navigation system to be used intraoperatively for navigated placement. Intraoperatively, the SPG microstimulator was implanted by completing the initial dissection with CT navigation, while the final position of the stimulator was verified by 3D CBCT. Those reconstructed images were then immediately matched with the preoperative CT scans with the digitally inserted SPG microstimulator. This method allowed for visual comparison of both CT scans and verified correct positioning of the SPG microstimulator. RESULTS: Twenty-four surgeries were performed using this new method of CT navigated assistance during SPG microstimulator implantation. Those results were compared to results of 21 patients previously implanted without the assistance of CT navigation. Using CT navigation during the initial dissection, an average distance reduction of 1.2 mm between the target point and electrode tip of the SPG microstimulator was achieved. Using the navigation software for navigated implantation and matching the preoperative planned scans with those performed post-operatively, the average distance was 2.17 mm with navigation, compared to 3.37 mm in the 28 surgeries without navigation. CONCLUSION: Results from this new procedure showed a significant reduction (p = 0.009) in the average distance from the SPG microstimulator to the desired target point. Therefore, a distinct improvement could be achieved in positioning of the SPG microstimulator through the use of intraoperative navigation during the initial dissection and by post-operative matching of pre- and post-operatively performed CBCT scans.

Bone cement allocation analysis in artificial cancellous bone structures.

BACKGROUND: One of the most serious adverse events potentially occurring during vertebroplasty is cement leakage. Associated risks for the patient could be reduced if cement filling is preoperatively planned. This requires a better understanding of cement flow behaviour. Therefore, the aim of the present study was to investigate bone cement distribution in artificial inhomogeneous cancellous bone structures during a simulated stepwise injection procedure. METHODS: Four differently coloured 1-mL cement portions were injected stepwise into six open-porous aluminum foam models with simulated leakage paths. Each model was subsequently cross-sectioned and high-resolution pictures were taken, followed by anatomical site allocation based on the assumption about a posterior insertion of the cannula. A radial grid consisting of 36 equidistant beams (0°-350°) was applied to evaluate the cement flow along each beam by measuring the radial length of each cement portion (total length) and of all four portions together (distance to border). Independently from the injection measurements, the viscosity of 20 cement portions was measured at time points corresponding to the start of the first and the end of the last injection. RESULTS: Despite some diffuse colour transitions at the borderlines, no interfusion between the differently coloured cement portions was observed. The two highest values for total length of each of the first three injected cement portions and for distance to border were indicated in directions anterior bilateral to the cannula along the 120°, 240° and 250° beams and posterolateral along the 60° beam. The two highest total lengths for the fourth cement portion were registered in the direction of the cannula along the 170° and 180° beams. Standard deviations of total length for each of the last three injected portions and for distance to border were with two highest values in directions anterior bilateral to the cannula along the 120°, 150°, 240° and 250° beams and opposite to the direction of the cannula along the 10° beam. The two highest values for the first cement portion were registered posterior bilateral to the cannula along the 70° and 350° beams. The values for averaged standard deviations of the total length of the fourth cement portion and the distance to border were significantly higher in comparison to the first cement portion (p ≤ 0.020). Dynamic viscosity at the start of the first injection was 343 ± 108 Pa∙s and increased to 659 ± 208 Pa∙s at the end of the fourth injection. CONCLUSION: The simulated leakage path seemed to be the most important adverse injection factor influencing the uniformity of cement distribution. Another adverse factor causing dispersion of this distribution was represented by the simulated bone marrow. However, the rather uniform distribution of the totally injected cement amount, considered as one unit, could be ascribed to the medium viscosity of the used cement. Finally, with its short waiting time of 45 s, the stepwise injection procedure was shown to be ineffective in preventing cement leakage.

Valence and Arousal Value of Visual Stimuli and Their Role in the Mitigation of Chronic Pain: What Is the Power of Pictures?

The present study investigated the pain-reducing effects of various pictures in a sample of 88 patients receiving inpatient treatment for chronic pain. We investigated whether the pain-attenuating effects of the pictures were mediated by picture valence, arousal, or change in subjective social support. The study was carried out over 4 consecutive days. Patients were presented with photographs of loved ones, strangers, landscapes, or optical illusions via digital albums and were asked to rate their pain intensity and their sensory and affective experience of pain immediately before and after viewing the pictures. They also evaluated the valence of the pictures and the extent to which they were arousing. Before and after participation in the study, patients provided information on their subjective social support. The valence attributed to the pictures varied; photographs of loved ones elicited the greatest pleasure. Pictures of varying emotional content and arousal value all reduced affective and sensory perceptions of pain. Viewing photographs of loved ones reduced pain intensity more than viewing other picture types. The association between picture type and decrease in pain intensity was mediated by picture valence. These findings suggest an easy to implement supplementary intervention that could be used in multidisciplinary pain treatment. PERSPECTIVE: To our knowledge, this is the first demonstration that pictures mitigate pain in chronic pain patients receiving treatment in a multidisciplinary pain center. The procedure could be used routinely to treat pain, particularly severe pain.

Bone cement flow analysis by stepwise injection through medical cannulas.

Cement leakage is a serious adverse event potentially occurring during vertebroplasty. Pre-operative in-silico planning of the cement filling process can help reducing complication rates related to leakage. This requires a better understanding of the cement flow along the whole injection path. Therefore, the aim of the present study was to analyze bone cement flow behavior by stepwise injections through medical cannulas. Sixteen cannulas were assigned to four groups for stepwise injection of differently colored cement portions of 1ml volume. Each group differed in the amount of injected cement portions with a range of 1-4ml. After cement curing longitudinal cross-sections of the cannulas were performed and high-resolution pictures taken. Based on these pictures, quadratic polynomial interpolation was applied to the marked intersections between the last two injected cement portions to calculate the leading coefficients. Leading coefficients in the groups with three cement portions (0.287 ± 0.078), four portions (0.243 ± 0.041) and two portions (0.232 ± 0.050) were comparable and significantly higher than the group with one cement portion (0.0032 ± 0.0004), p ≤ 0.016. Based on these findings, cement flow through medical cannulas can be considered as predictable and can therefore be excluded as a source of risk for possible cement leakage complications during vertebroplasty procedures.

Reduction of cement leakage by sequential PMMA application in a vertebroplasty model.

PURPOSE: Leakage is the most common complication of percutaneous cement augmentation of the spine. The viscosity of the polymethylmethacrylate (PMMA) cement is strongly correlated with the likelihood of cement leakage. We hypothesized that cement leakage can be reduced by sequential cement injection in a vertebroplasty model. METHODS: A standardized vertebral body substitute model, consisting of aluminum oxide foams coated by acrylic cement with a preformed leakage path, simulating a ventral vein, was developed. Three injection techniques of 6 ml PMMA were assessed: injection in one single step (all-in-one), injection of 1 ml at the first and 5 ml at the second step with 1 min latency in-between (two-step), and sequential injection of 0.5 ml with 1-min latency between the sequences (sequential). Standard PMMA vertebroplasty cement was used; each injection type was tested on ten vertebral body substitute models with two possible leakage paths per model. Leakage was assessed by radiographs using a zonal graduation: intraspongious = no leakage and extracortical = leakage. RESULTS: The leakage rate was significantly lower in the "sequential" technique (2/20 leakages) followed by "two-step" (15/20) and "all-in-one" (20/20) techniques (p < 0.001). The RR for a cement leakage was 10.0 times higher in the "all-in-one" compared to the "sequential" group (95 % confidence intervals 2.7-37.2; p < 0.001). CONCLUSIONS: The sequential cement injection is a simple approach to minimize the risk for leakage. Taking advantage of the temperature gradient between body and room temperature, it is possible to increase the cement viscosity inside the vertebra while keeping it low in the syringe. Using sequential injection of small cement volumes, further leakage paths are blocked before further injection of the low-viscosity cement.

Multiphasic modelling of bone-cement injection into vertebral cancellous bone.

Percutaneous vertebroplasty represents a current procedure to effectively reinforce osteoporotic bone via the injection of bone cement. This contribution considers a continuum-mechanically based modelling approach and simulation techniques to predict the cement distributions within a vertebra during injection. To do so, experimental investigations, imaging data and image processing techniques are combined and exploited to extract necessary data from high-resolution µCT image data. The multiphasic model is based on the Theory of Porous Media, providing the theoretical basis to describe within one set of coupled equations the interaction of an elastically deformable solid skeleton, of liquid bone cement and the displacement of liquid bone marrow. The simulation results are validated against an experiment, in which bone cement was injected into a human vertebra under realistic conditions. The major advantage of this comprehensive modelling approach is the fact that one can not only predict the complex cement flow within an entire vertebra but is also capable of taking into account solid deformations in a fully coupled manner. The presented work is the first step towards the ultimate and future goal of extending this framework to a clinical tool allowing for pre-operative cement distribution predictions by means of numerical simulations.

Neuropathic sensory symptoms: association with pain and psychological factors.

BACKGROUND: A large number of population-based studies of chronic pain have considered neuropathic sensory symptoms to be associated with a high level of pain intensity and negative affectivity. The present study examines the question of whether this association previously found in non-selected samples of chronic pain patients can also be found in chronic pain patients with underlying pathology of neuropathic sensory symptoms. METHODS: Neuropathic sensory symptoms in 306 patients with chronic pain diagnosed as typical neuropathic pain, radiculopathy, fibromyalgia, or nociceptive back pain were assessed using the Pain DETECT Questionnaire. Two separate cluster analyses were performed to identify subgroups of patients with different levels of self-reported neuropathic sensory symptoms and, furthermore, to identify subgroups of patients with distinct patterns of neuropathic sensory symptoms (adjusted for individual response bias regarding specific symptoms). RESULTS: ANOVA (analysis of variance) results in typical neuropathic pain, radiculopathy, and fibromyalgia showed no significant differences between the three levels of neuropathic sensory symptoms regarding pain intensity, pain chronicity, pain catastrophizing, pain acceptance, and depressive symptoms. However, in nociceptive back pain patients, significant differences were found for all variables except pain chronicity. When controlling for the response bias of patients in ratings of symptoms, none of the patterns of neuropathic sensory symptoms were associated with pain and psychological factors. CONCLUSION: Neuropathic sensory symptoms are not closely associated with higher levels of pain intensity and cognitive-emotional evaluations in chronic pain patients with underlying pathology of neuropathic sensory symptoms. The findings are discussed in term of differential response bias in patients with versus without verified neuropathic sensory symptoms by clinical examination, medical tests, or underlying pathology of disease. Our results lend support to the importance of using adjusted scores, thereby eliminating the response bias, when investigating self-reported neuropathic symptoms by patients.

Does the cement stiffness affect fatigue fracture strength of vertebrae after cement augmentation in osteoporotic patients?

PURPOSE: Normal progression of osteoporosis or the rigid reinforcement of the fractured vertebral body with polymethyl methacrylate (PMMA) cement is being discussed as a cause for adjacent-level fractures after vertebroplasty. The purpose of this study was to investigate whether augmentation with low stiffness cement can decrease the risk of adjacent-level fractures in low-quality bone. METHODS: Eighteen female osteoporotic lumbar specimens (L1-L5) were harvested and divided into three groups according to bone mineral density: (I) native; (II) PMMA; (III) modified PMMA (lower stiffness). For the PMMA and modified PMMA groups, a compression fracture was first mechanically induced in L3, and then the fracture received vertebroplasty treatment. The cement stiffness reduction of the modified PMMA group was achieved via an addition of 8 mL of serum to the typical PMMA base. All specimens were exposed to cyclic loading (4 Hz) and a stepwise increasing applied peak force. Cement stiffness was tested according to ISO 5833. RESULTS: A 51% decrease in cement stiffness was achieved in the modified PMMA group (954 ± 141 vs. 1,937 ± 478 MPa, p < 0.001). Fatigue fracture force (the force level during cyclic loading at which the deformation experienced a sudden increase; FFF) was significantly affected by bone quality (r (2) = 0.39, p = 0.006) and by the initial fracture force (the force necessary to create the initial fracture in L3 prior to augmentation; r (2) = 0.82, p < 0.001). Using initial fracture force as a covariate, the FFF of the modified PMMA group (1,764 ± 49 N) was significantly higher than in the PMMA group (1,544 ± 55 N; p = 0.03). CONCLUSIONS: A possible method to reduce adjacent-level fractures after vertebroplasty in patients with reduced bone quality could be the use of a lower modulus cement. Therefore, mixing cement with biocompatible fluids could prove useful to tailor cement properties in the operating theater.

Ex vivo evaluation of the polymerization temperatures during cement augmentation of proximal femoral nail antirotation blades.

BACKGROUND: Previous studies have clearly demonstrated superior biomechanical behavior of augmented proximal femoral nail antirotation (PFNA) blades compared with nonaugmented ones with respect to implant cutout. Nevertheless, there is concern about thermal bone necrosis due to exothermic curing of polymethylmethacrylate (PMMA)-based bone cements. The objective of this study was to quantify the temperatures arising around perforated titanium PFNA blades when augmenting with PMMA. METHODS: Cylindrical samples from six pairs of fresh frozen human cadaveric femoral heads implanted with a PFNA blade were placed in a 37°C water bath and augmented with 3 mL and 6 mL PMMA. During augmentation, temperatures were measured using six K-type thermocouples that were placed at controlled distances around the implant. With the help of high-resolution quantitative computed tomography images, the locations of all thermocouples with respect to the cement-bone interface were reconstructed. RESULTS: No temperatures higher than 45°C were measured in the interface region and the surrounding cement-free cancellous bone. In the same regions, the longest exposure time above 41°C was 8.5 minutes and was measured in a 6-mL sample. Average maximum temperature was significantly lower for the 3-mL group compared with the 6-mL group (p = 0.017). CONCLUSION: The results of this study suggest that augmentation of titanium PFNA blades is not associated with a risk of thermal bone necrosis when using up to 6 mL of PMMA. However, larger amounts of cement lead to higher temperatures. PMMA application should therefore be kept low to minimally alter the biological system.

Potential of polymethylmethacrylate cement-augmented helical proximal femoral nail antirotation blades to improve implant stability--a biomechanical investigation in human cadaveric femoral heads.

BACKGROUND: Cement augmentation may improve fixation stability and reduce cut-out rate in the treatment of intertrochanteric hip fractures. The aim of this study was to compare the number of cycles to failure of polymethylmethacrylate (PMMA)-augmented helical blades with nonaugmented ones in human cadaveric femoral heads. METHODS: Six pairs of cadaveric femoral heads were instrumented with a perforated proximal femoral nail antirotation blade. Within each pair, one blade was augmented using 3 mL of PMMA. All specimens underwent cyclic axial loading under physiologic conditions.Starting at 1,000 N, the load was monotonically increased by 0.1 N/cycle until construct failure occurred. To monitor the migration of the blade, anteroposterior radiographs were taken at 250 cycle increments. Nonparametric test statistics were done to calculate correlations and identify differences between study groups. RESULTS: Inducing failure required a significantly higher number of cycles in the augmented group (p = 0.028). Bone mineral density was significantly related with the number of cycles to failure in nonaugmented specimens (p 0.001, R2 = 0.97), but not in the augmented group (p = 0.91, R2 = 0.34). CONCLUSION: Implant augmentation with small amounts of PMMA enhances the cut-out resistance in proximal femoral fractures. Especially in osteoporotic bone, the procedure may improve patient care.