Search

Feline FJA ter Bruggen,1 W Ken Redekop,2 Dirk L Stronks,1 Frank JPM Huygen1 1Department of Anesthesiology, Center for Pain Medicine, Erasmus MC, Rotterdam, the Netherlands; 2Department of Health Technology Assessment, Erasmus School of Health Policy & Management, Erasmus University Rotterdam, Rotterdam, the NetherlandsCorrespondence: Feline FJA ter Bruggen Tel +31 6 40962334Email ftbruggen@gmail.com; f.terbruggen@erasmusmc.nlObjective: The success of neurostimulation depends partly on the amount of coverage of the neurostimulation-induced paresthesia of the painful area. This is often achieved by asking feedback from patients intraoperatively. If sedation analgesia is used, it is important that the patient is comfortable during sedation and easily arousable. If the patient is not well sedated or experiences residual effects of the sedation during testing, this can directly influence the ideal placement of the leads and indirectly the long-term effect of the treatment. It is our hypothesis that the quality of the sedation is directly coupled to the adequacy of lead placement and in this way in the result of the treatment. Dexmedetomidine is known for its easy production of arousable sedation. The aim of the present study was to compare the long-term effect of using dexmedetomidine versus propofol during the implantation of a neurostimulator.Materials and Methods: This is a post-trial follow-up analysis of the DexMedPro cohort. The primary outcome was global perceived effect (GPE). The secondary outcomes were the course of pain intensity, the emotional and physical functioning at the time of follow-up, and the course of neurostimulation treatment. In this study, we used the patient satisfaction with sedation as a measure for sedation quality.Results: Regarding the GPE, no statistically significant differences were found between the experimental groups in either subscale (ie, recovery (p=0.82) and satisfaction with the neurostimulation treatment at follow-up (p=0.06)). The same was found regarding the secondary parameters. A correlation was found between patient satisfaction with sedation during the lead implantation (side effects and procedural recall) and satisfaction at follow-up.Conclusion: Regarding the long-term efficacy of neurostimulation treatment, no statistically significant differences were found between the dexmedetomidine and the propofol group. We observed a trend towards greater satisfaction with the neurostimulation treatment at follow-up in the dexmedetomidine group, compared to the propofol group.Keywords: dexmedetomidine, propofol, chronic pain, neurostimulation, follow-up, retrospective studies

This double-blind, randomized, controlled trial investigated the effect of the phosphodiesterase-5 inhibitor tadalafil on the microcirculation in patients with cold Complex Regional Pain Syndrome (CRPS) in one lower extremity.~Background~Background~Twenty-four patients received 20 mg tadalafil or placebo daily for 12 weeks. The patients also participated in a physical therapy program. The primary outcome measure was temperature difference between the CRPS side and the contralateral side, determined by measuring the skin temperature with videothermography. Secondary outcomes were: pain measured on a Visual Analogue Scale, muscle force measured with a MicroFet 2 dynamometer, and level of activity measured with an Activity Monitor (AM) and walking tests.~Methods~Methods~At the end of the study period, the temperature asymmetry was not significantly reduced in the tadalafil group compared with the placebo group, but there was a significant and clinically relevant reduction of pain in the tadalafil group. Muscle force improved in both treatment groups and the AM revealed small, non-significant improvements in time spent standing, walking, and the number of short walking periods.~Results~Results~Tadalafil may be a promising new treatment for patients that have chronic cold CRPS due to endothelial dysfunction, and deserves further investigation.~Conclusion~Conclusions~The registration number in the Dutch Trial Register is ISRCTN60226869.~Trial Registration~Background [ABSTRACT FROM AUTHOR]

Previously, we showed that serum soluble interleukin-2 receptor (sIL-2R) levels, a marker for T-cell activation, were higher in complex regional pain syndrome (CRPS) patients than in healthy controls, suggesting pathogenic T-cell activation in CRPS. Additionally, sIL-2R levels discriminated well between CRPS and healthy controls with a high sensitivity (90%) and specificity (89.5%), suggesting a possible role for sIL-2R in the diagnosis of CRPS. In order to further validate this marker in the diagnostic workup of CRPS, we conducted this prospective cohort study in which we determined sIL-2R levels in patients that were referred to our tertiary referral center with a suspicion of CRPS in a limb, and subsequently compared sIL-2R levels between the patients that were diagnosed with CRPS (CRPS group) and those who were not (no CRPS group). A group of anonymous blood bank donors were used as a healthy control group. Furthermore, we explored the relationship between sIL-2R and CRPS disease severity using the CRPS severity score. Median sIL-2R levels of both the CRPS group (2809.0 pg/ml; Q3-Q1: 3913.0-1589.0) and no CRPS group (3654.0 pg/ml; Q3-Q1: 4429.0-2095.5) were significantly higher than that of the control group (1515.0 pg/ml; Q3-Q1: 1880.0-1150.0): CRPS vs. controls, p < .001; no CRPS vs. controls, p < 0.001. Serum sIL-2R levels did not differ significantly between the CRPS and no CRPS group. A statistically significant negative correlation was observed between sIL-2R levels and the CRPS severity score ( r s = -0.468, p = 0.024). Our results confirm our previous findings of higher sIL-2R levels in CRPS patients than in healthy controls. We further showed that serum sIL-2R cannot differentiate between CRPS and other pain conditions of a limb in a tertiary referral setting. Interestingly, a negative correlation was found between sIL-2R and CRPS disease severity; this finding warrants further research into the relationship between sIL-2R and CRPS disease severity., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 K. D. Bharwani et al.)

Objective: Although complex regional pain syndrome (CRPS) of the knee is comparable to CRPS of the ankle/foot at time of diagnosis, no reports are available concerning the course of knee CRPS. Therefore, this study investigated the clinical course in terms of the symptoms and signs, health-related quality of life (HR-QoL), and work status of patients diagnosed with CRPS of the knee., Design: Observational, descriptive study., Setting: Single-center study., Subjects: Patients with CRPS of the knee., Methods: Patients self-reported their past and current CRPS symptoms, HR-QoL, and work status; all underwent a physical examination. A comparison was made of changes in symptoms over time between patients with CRPS of the knee and those with CRPS of more distal locations., Results: In total, 32 patients were enrolled. The follow-up time was 11.5 ± 6.29 years since diagnosis, and symptoms and signs showed a significant decrease over time. Twelve patients (37.5%) rated their health as (generally) positive. Patients who were still able to work (31.3%) stated that their physical health gave them at least some problems in the performance of their job. A change in symptoms occurred significantly less often in CRPS of the knee., Conclusions: CRPS of the knee changes in terms of symptoms over time, but significantly less than CRPS of other locations. A change in work status was reported in 82% of the patients due to their CRPS, and in 91%, the pain interfered with their daily life. CRPS of the knee is a painful condition with persistent symptoms causing a diminished HR-QoL., (© 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The immune system has long been thought to be involved in the pathophysiology of complex regional pain syndrome (CRPS). However, not much is known about the role of the immune system and specifically T-cells in the onset and maintenance of this disease. In this study, we aimed to evaluate T-cell activity in CRPS by comparing blood soluble interleukin-2 receptor (sIL-2R) levels between CRPS patients and healthy controls. CRPS patients had statistically significant elevated levels of sIL-2R as compared to healthy controls (median sIL-2R levels: 4151 pg/ml (Q3 - Q1 = 5731 pg/ml - 3546 pg/ml) versus 1907 pg/ml (Q3 - Q1: 2206 pg/ml - 1374 pg/ml), p < 0.001, resp.). Furthermore, sIL-2R level seems to be a good discriminator between CRPS patients and healthy controls with a high sensitivity (90%) and specificity (89.5%). Our finding indicates increased T-cell activity in patients with CRPS. This finding is of considerable relevance as it could point towards a T-cell-mediated inflammatory process in this disease. This could pave the way for new anti-inflammatory therapies in the treatment of CRPS. Furthermore, sIL-2R could be a promising new marker for determining inflammatory disease activity in CRPS.

Objective: To compare the phenotypes of patients with complex regional pain syndrome (CRPS) of the knee to those with CRPS of the ankle/foot., Setting: A retrospective study., Subjects: Patients with CRPS of the knee and patients with CRPS of the ankle/foot., Methods: We used electronic patient databases to identify patients with CRPS of the knee and patients with CRPS of the ankle/foot. The following variables were recorded: age, gender, duration of complaints, initial injury, and symptoms and signs. Frequency distributions and statistical significant differences between the groups were determined., Results: Included were 50 patients with CRPS of the knee and 64 patients with CRPS of the ankle/foot. These patients were all diagnosed with CRPS according to the criteria used at the time of diagnosis. No significant differences were found in demographic characteristics. A few symptoms and signs appeared to be proportionally more prevalent in patients with CRPS of the ankle/foot. However, patients with CRPS of the knee suffered significantly longer from the disease than patients with CRPS of the ankle/foot., Conclusions: Some signs and symptoms appeared to be statistically significantly more prevalent in CRPS of the ankle/foot than in CRPS confined to the knee. We conclude that the phenotypes of CRPS confined to the knee and CRPS of the ankle/foot are comparable, but not identical. This can be a reason why CRPS in patients with pain of the knee, that is disproportionate to the initial trauma, is sometimes not recognized., (© 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Non-adherence to pain medication is common and may jeopardize the effect of prescribed therapy in chronic pain patients. We investigated the effect of medication-specific education on pain medication adherence., Methods: One hundred eligible chronic pain patients were randomized into a control or intervention group. They were assessed during an intake (T0) and two follow-up visits after 4 (T1) and 10 weeks (T2). Immediately after T1, patients in the intervention group additionally watched a video and received written information about the medication prescribed. At T1 and T2, medication adherence according to self-reporting including the Morisky Medication Adherence Scale, prescription knowledge, pain intensity numeric rating scale (NRS), concerns about medication, and patient satisfaction were recorded., Results: Experimental group (control versus intervention) did not significantly contribute to the prediction of medication adherence at T2 (P = 0.38). The non-adherence rates were 31% and 43% at T1 and 53% and 49% at T2 in the control and intervention group, respectively. Changes in patients' knowledge of the prescription were attributable to the intervention (P < 0.01). No other significant differences were identified., Conclusions: Medication-specific education did increase knowledge of the prescribed therapy but did not improve adherence or treatment outcome parameters. There was no association between medication adherence and pain treatment outcome., (© 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Autoimmunity has been suggested as one of the pathophysiologic mechanisms that may underlie complex regional pain syndrome (CRPS). Screening for antinuclear antibodies (ANA) is one of the diagnostic tests, which is usually performed if a person is suspected to have a systemic autoimmune disease. Antineuronal antibodies are autoantibodies directed against antigens in the central and/or peripheral nervous system. The aim of this study was to compare the prevalence of these antibodies in CRPS patients with the normal values of those antibodies in the healthy population. Twenty seven (33%) of the 82 CRPS patients of whom serum was available showed a positive ANA test. This prevalence is significantly higher than in the general population. Six patients (7.3%) showed a positive result for typical antineuronal antibodies. This proportion, however, does not deviate from that in the general population. Our findings suggest that autoantibodies may be associated with the pathophysiology of CRPS, at least in a subset of patients. Further research is needed into defining this subset and into the role of autoantibodies in the pathogenesis of CRPS.

Background: Surgery has wide ranging immunomodulatory properties of which the mechanism is poorly understood. In order to investigate how different types of surgery influence inflammation, we designed a longitudinal observational study investigating two inflammatory profiles of two separate patient groups undergoing gynaecological operations of differing severity. In addition to measuring the well known inflammatory markers neopterin and IL-6, we also determined the kynurenine/tryptophan ratio. This study was a prospective, single center, two-armed observational study involving 28 female patients. Plasma levels of tryptophan, kynurenine, neopterin and IL-6 were determined from samples taken at: 24 hrs pre-operative, prior to induction, ten minutes before the operation was expected to end, and at 24 and 96 hours post operative in patients undergoing abdominal hysterectomy and vulvectomy., Results: There were 15 and 13 patients included in the vulvectomy and abdominal hysterectomy groups, respectively. In this study we show that anesthesia and surgery significantly increases the enzyme activity of indoleamine 2, 3 dioxygenase (IDO) as measured by the kynurenine/tryptophan ratio (P=0.003), while maintaining stable neopterin levels. However, abdominal hysterectomy causes a considerable IL-6 increase (P<0.001)., Conclusion: Surgery and associated anesthesia cause a significant tryptophan level decrease while significantly increasing IDO activity. Both types of surgery produce nearly identical neopterin time curve relationships, with no significant change occurring in either group. However, even though neopterin is unaffected by the severity of surgery, IL-6 responded to surgical invasiveness by revealing a significant increase during abdominal hysterectomy.

The microcirculation appears to be impaired in cold chronic complex regional pain syndrome (CRPS). This double-blind, placebo-controlled, randomized trial investigated the effect of the nitric oxide (NO) donor isosorbide dinitrate (ISDN) on the peripheral blood flow in patients with chronic CRPS. Twenty-four patients received 1% ISDN in Vaseline or a placebo ointment applied to the dorsum of the affected hand four times daily for 10 weeks. The patients participated in a physical therapy program to improve activity. The primary outcome measure was blood distribution in the affected extremity, which was determined by measuring the skin temperature using videothermography. We also measured NO and endothelin-1 concentrations in blister fluid, pain using the visual analog scale, and activity limitations using an upper limb activity monitor and the Disabilities of Arm Shoulder and Hand Questionnaire. ISDN failed to produce a significant improvement in temperature asymmetry in chronic cold CRPS patients, and it did not result in the expected reduction in pain and increase in activity compared with placebo either. There may be other central or peripheral factors contributing to the disturbed vasodynamics in cold chronic CRPS that are not influenced by NO substitution. This study does not show an improvement of the regional blood distribution by ISDN in the involved extremity of patients with cold-type CRPS.

Adherence to analgesics in cancer patients has scarcely been studied. In this study, the Medication Event Monitoring System (MEMS) and medication diaries were compared with respect to feasibility and adherence measurements. Forty-six outpatients with nociceptive pain caused by cancer were asked to use MEMS for their analgesics and to record their medication usage in a diary for four weeks. Seventy-nine percent of the patients used MEMS for the full four-week period; 70% did so for the diary. The majority of patients were satisfied with both MEMS and diary. Adherence data assessed by MEMS and diary were comparable. Patients used the amount of analgesics adequately (taking adherence: 87%) but took them irregularly (timing adherence: 53%). Subgroup analyses in patients using single and multiple analgesic regimens confirmed the comparable suitability of both methods. MEMS and a medication diary are equally useful for analgesic adherence measurement in cancer patients with pain.