Prevalence of post-traumatic neuropathic pain after digital nerve repair and finger amputation.

INTRODUCTION: Post-traumatic neuropathic pain is a major factor affecting the quality of life after finger trauma and is reported with considerable variance in the literature. This can partially be attributed to the different methods of determining neuropathic pain. The Douleur Neuropathique 4 (DN4) has been validated to be a reliable and non-invasive tool to assess the presence of neuropathic pain. This study investigated the prevalence of neuropathic pain after finger amputation or digital nerve repair using the DN4 questionnaire. METHODS: Patients with finger amputation or digital nerve repair were identified between 2011 and 2018 at our institution. After a minimal follow-up of 12 months, the short form DN4 (S-DN4) was used to assess neuropathic pain. RESULTS: A total of 120 patients were included: 50 patients with 91 digital amputations and 70 patients with 87 fingers with digital nerve repair. In the amputation group, 32% of the patients had pain, and 18% had neuropathic pain. In the digital nerve repair group, 38% of the patients had pain, and 14% had neuropathic pain. Secondly, of patient-, trauma-, and treatment-specific factors, only the time between trauma and surgery had a significant negative influence on the prevalence of neuropathic pain in patients with digital nerve repair. CONCLUSION: This study shows that persistent pain and neuropathic pain are common after finger trauma with nerve damage. One of the significant prognostic factors in developing neuropathic pain is treatment delay between trauma and time of digital nerve repair, which is of major clinical relevance for surgical planning of these injuries.

Denying the Truth Does Not Change the Facts: A Systematic Analysis of Pseudoscientific Denial of Complex Regional Pain Syndrome.

PURPOSE: Several articles have claimed that complex regional pain syndrome (CRPS) does not exist. Although a minority view, it is important to understand the arguments presented in these articles. We conducted a systematic literature search to evaluate the methodological quality of articles that claim CRPS does not exist. We then examined and refuted the arguments supporting this claim using up-to-date scientific literature on CRPS. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane CENTRAL databases. Inclusion criteria for articles were (a) a claim made that CRPS does not exist or that CRPS is not a distinct diagnostic entity and (b) support of these claims with subsequent argument(s). The methodological quality of articles was assessed if possible. RESULTS: Nine articles were included for analysis: 4 narrative reviews, 2 personal views, 1 letter, 1 editorial and 1 case report. Seven points of controversy were used in these articles to argue that CRPS does not exist: 1) disagreement with the label "CRPS"; 2) the "unclear" pathophysiology; 3) the validity of the diagnostic criteria; 4) CRPS as a normal consequence of immobilization; 5) the role of psychological factors; 6) other identifiable causes for CRPS symptoms; and 7) the methodological quality of CRPS research. CONCLUSION: The level of evidence for the claim that CRPS does not exist is very weak. Published accounts concluding that CRPS does not exist, in the absence of primary evidence to underpin them, can harm patients by encouraging dismissal of patients' signs and symptoms.

Serum Soluble Interleukin-2 Receptor Does Not Differentiate Complex Regional Pain Syndrome from Other Pain Conditions in a Tertiary Referral Setting.

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.

The longitudinal relationships between pain severity and disability versus health-related quality of life and costs among chronic low back pain patients.

PURPOSE: Previous studies found higher levels of pain severity and disability to be associated with higher costs and lower health-related quality of life. However, these findings were based on cross-sectional data and little is known about the longitudinal relationships between pain severity and disability versus health-related quality of life and costs among chronic low back pain patients. This study aims to cover this knowledge gap by exploring these longitudinal relationships in a consecutive cohort. METHODS: Data of 6316 chronic low back pain patients were used. Measurements took place at 3, 6, 9, and 12 months. Pain severity (Numeric pain rating scale; range: 0-100), disability (Oswestry disability index; range: 0-100), health-related quality of life (EQ-5D-3L: range: 0-1), societal and healthcare costs (cost questionnaire) were measured. Using linear generalized estimating equation analyses, longitudinal relationships were explored between: (1) pain severity and health-related quality of life, (2) disability and health-related quality of life, (3) pain severity and societal costs, (4) disability and societal costs, (5) pain severity and healthcare costs, and (6) disability and healthcare costs. RESULTS: Higher pain and disability levels were statistically significantly related with poorer health-related quality of life (pain intensity: - 0.0041; 95% CI - 0.0043 to - 0.0039; disability: - 0.0096; 95% CI - 0.0099 to - 0.0093), higher societal costs (pain intensity: 7; 95% CI 5 to 8; disability: 23; 95% CI 20 to 27) and higher healthcare costs (pain intensity: 3; 95% CI 2 to 4; disability: 9; 95% CI 7 to 11). CONCLUSION: Pain and disability were longitudinally related to health-related quality of life, societal costs, and healthcare costs. Disability had a stronger association with all outcomes compared to pain.

Diagnosing complex regional pain syndrome using an electronic nose, a pilot study.

OBJECTIVE: Complex regional pain syndrome (CRPS) is a complication after surgery or trauma and is characterized by a continuing regional pain in a distal extremity. The pain is disproportionate in severity and duration in relation to the preceding trauma. Currently, the diagnosis is based on the patients' signs and symptoms. There is no objective clinically applicable test available to confirm the diagnosis of CRPS, however this could contribute to a more reliable and valid diagnosis. Since the treatment of CRPS differs from that of other types of pain this could thereby lead to earlier and (more) appropriate treatment and possibly to lower medical costs. The Aeonose™ is a diagnostic test device which detects volatile organic profiles in exhaled air. Exhaled breath analysis using an electronic nose has been successfully applied to differentiate between sick and healthy persons for various indications. This study was a feasibility study in which we investigated whether the Aeonose™ is able to measure a difference in the volatome of CRPS patients compared to the volatome of healthy controls. DESIGN: Prospective observational study. SETTING: University Center for Pain Medicine. SUBJECTS: Adult patients diagnosed with CRPS according to the latest IASP criteria (n = 36) and matched healthy controls (n = 36). METHODS: Breath profiles were sampled by breathing in and out through the Aeonose™. Data were compressed using a Tucker3-like solution and subsequently used for training an artificial neural network together with the classification 'CRPS: Yes' or 'CRPS: No'. Cross-validation was applied using the leave-10%-out method. RESULTS: Data of the 72 participants were analyzed, resulting in a sensitivity of 83% (95% CI 67%-93%), specificity of 78% (95% CI 60%-89%), and an overall accuracy of 81%. CONCLUSIONS: This study suggests that the Aeonose™ can possibly distinguish patients with CRPS from healthy controls based on analysis of their volatome (MEC-2014-149).

Preferred frequencies and waveforms for spinal cord stimulation in patients with complex regional pain syndrome: A multicentre, double-blind, randomized and placebo-controlled crossover trial.

BACKGROUND: Conventional tonic spinal cord stimulation (SCS) is an effective treatment for patients with therapy-resistant complex regional pain syndrome (CRPS). Although the therapeutic effect of SCS can diminish over time due to tolerance, pain control can be regained by changing the pulse width and the amplitude and/or by increasing the stimulation frequency. This multicentre, double-blind, randomized and placebo-controlled crossover trial was conducted to investigate whether more effective pain reduction is achieved with different frequencies (trial registration, current controlled trials, ISRCTN 36655259). METHODS: The investigated settings are as follows: standard 40, 500, 1200 Hz, burst and placebo stimulation. All five were programmed in random order during the 10-week crossover period (2 weeks/setting). The primary outcome parameters were scores on the visual analogue scale (VAS), McGill Pain Questionnaire (MPQ) and the Global Perceived Effect (GPE); at the end of the crossover period, patients decided which SCS setting they preferred. A linear mixed models analysis was performed in 29 patients who completed the crossover trial. RESULTS: Significant pain reduction and GPE satisfaction was achieved with four SCS settings compared with placebo stimulation, and these four settings did not differ significantly from each other. Standard stimulation was preferred by 48% of the patients, while 52% preferred non-standard stimulation. Other than pain reduction, factors such as user-friendliness, comfort and recharging time may have influenced the patient's final decision for the preferred stimulation setting. CONCLUSIONS: Apparently, for various reasons, patients have a preference for different SCS setting. Therefore, future neuromodulation should aim to implement customized individual patient care by incorporating all stimulation options in one device. SIGNIFICANCE: This study demonstrates that standard frequency SCS is an effective therapy for patients with CRPS. However, it also demonstrates that patients can often gain better pain reduction with non-standard frequencies of SCS. Furthermore, it shows that the preferred stimulation setting is not solely driven by the amount of pain reduction, but is also influenced by which stimulation setting feels most comfortable and provides the best user-friendliness. Therefore, we strive to maximize the therapeutic effects of SCS in as many patients as possible. This can be achieved with customized individual patient care by incorporating the various frequencies and waveforms into one single device.

Randomized sham-controlled, double-blind, multicenter clinical trial on the effect of percutaneous radiofrequency at the ramus communicans for lumbar disc pain.

BACKGROUND: Investigate the effect of percutaneous radiofrequency compared to a sham procedure, applied to the ramus communicans for treatment of lumbar disc pain. METHODS: Randomized sham-controlled, double-blind, crossover, multicenter clinical trial. Multidisciplinary pain centres of two general hospitals. Sixty patients aged 18 or more with medical history and physical examination suggestive for lumbar disc pain and a reduction of two or more on a numerical rating scale (0-10) after a diagnostic ramus communicans test block. Treatment group: percutaneous radiofrequency treatment applied to the ramus communicans; sham: same procedure except radiofrequency treatment. PRIMARY OUTCOME MEASURE: pain reduction. Secondary outcome measure: Global Perceived Effect. RESULTS: No statistically significant difference in pain level over time between the groups, as well as in the group was found; however, the factor period yielded a statistically significant result. In the crossover group, 11 out of 16 patients experienced a reduction in NRS of 2 or more at 1 month (no significant deviation from chance). No statistically significant difference in satisfaction over time between the groups was found. The independent factors group and period also showed no statistically significant effects. The same applies to recovery: no statistically significant effects were found. CONCLUSIONS: The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected. Post hoc analysis revealed that none of the investigated parameters contributed to the prediction of a significant pain reduction. SIGNIFICANCE: Interrupting signalling through the ramus communicans may interfere with the transition of painful information from the discs to the central nervous system. Methodological differences exist in studies evaluating the efficacy of radiofrequency treatment for lumbar disc pain. A randomized, sham-controlled, double-blind, multicenter clinical trial on the effect of radiofrequency at the ramus communicans for lumbar disc pain was conducted. The null hypothesis of no difference in pain reduction and in Global Perceived Effect between the treatment and sham group cannot be rejected.

Systematic review of patient history and physical examination to diagnose chronic low back pain originating from the facet joints.

Patient history and physical examination are frequently used procedures to diagnose chronic low back pain (CLBP) originating from the facet joints, although the diagnostic accuracy is controversial. The aim of this systematic review is to determine the diagnostic accuracy of patient history and/or physical examination to identify CLBP originating from the facet joints using diagnostic blocks as reference standard. We searched MEDLINE, EMBASE, CINAHL, Web of Science and the Cochrane Collaboration database from inception until June 2016. Two review authors independently selected studies for inclusion, extracted data and assessed the risk of bias. We calculated sensitivity and specificity values, with 95% confidence intervals (95% CI). Twelve studies were included, in which 129 combinations of index tests and reference standards were presented. Most of these index tests have only been evaluated in single studies with a high risk of bias. Four studies evaluated the diagnostic accuracy of the Revel's criteria combination. Because of the clinical heterogeneity, results were not pooled. The published sensitivities ranged from 0.11 (95% CI 0.02-0.29) to 1.00 (95% CI 0.75-1.00), and the specificities ranged from 0.66 (95% CI 0.46-0.82) to 0.91 (95% CI 0.83-0.96). Due to clinical heterogeneity, the evidence for the diagnostic accuracy of patient history and/or physical examination to identify facet joint pain is inconclusive. Patient history and physical examination cannot be used to limit the need of a diagnostic block. The validity of the diagnostic facet joint block should be studied, and high quality studies are required to confirm the results of single studies. SIGNIFICANCE: Patient history and physical examination cannot be used to limit the need of a diagnostic block. The validity of the diagnostic facet joint block should be studied, and high quality studies are required to confirm the results of single studies.

Characterizing human skin blood flow regulation in response to different local skin temperature perturbations.

Small nerve fibers regulate local skin blood flow in response to local thermal perturbations. Small nerve fiber function is difficult to assess with classical neurophysiological tests. In this study, a vasomotor response model in combination with a heating protocol was developed to quantitatively characterize the control mechanism of small nerve fibers in regulating skin blood flow in response to local thermal perturbation. The skin of healthy subjects' hand dorsum (n=8) was heated to 42°C with an infrared lamp, and then naturally cooled down. The distance between the lamp and the hand was set to three different levels in order to change the irradiation intensity on the skin and implement three different skin temperature rise rates (0.03°C/s, 0.02°C/s and 0.01°C/s). A laser Doppler imager (LDI) and a thermographic video camera recorded the temporal profile of the skin blood flow and the skin temperature, respectively. The relationship between the skin blood flow and the skin temperature was characterized by a vasomotor response model. The model fitted the skin blood flow response well with a variance accounted for (VAF) between 78% and 99%. The model parameters suggested a similar mechanism for the skin blood flow regulation with the thermal perturbations at 0.03°C/s and 0.02°C/s. But there was an accelerated skin vasoconstriction after a slow heating (0.01°C/s) (p-value<0.05). An attenuation of the skin vasodilation was also observed in four out of the seven subjects during the slow heating (0.01°C/s). Our method provides a promising way to quantitatively assess the function of small nerve fibers non-invasively and non-contact.

Randomised sham-controlled double-blind multicentre clinical trial to ascertain the effect of percutaneous radiofrequency treatment for lumbar facet joint pain.

AIMS: The aim of this study was to compare the effect of a percutaneous radiofrequency heat lesion at the medial branch of the primary dorsal ramus with a sham procedure, for the treatment of lumbar facet joint pain. PATIENTS AND METHODS: A randomised sham-controlled double blind multicentre trial was carried out at the multidisciplinary pain centres of two hospitals. A total of 60 patients aged > 18 years with a history and physical examination suggestive of facet joint pain and a decrease of ≥ 2 on a numerical rating scale (NRS 0 to 10) after a diagnostic facet joint test block were included. In the treatment group, a percutaneous radiofrequency heat lesion (80oC during 60 seconds per level) was applied to the medial branch of the primary dorsal ramus. In the sham group, the same procedure was undertaken without for the radiofrequency lesion. Both groups also received a graded activity physiotherapy programme. The primary outcome measure was decrease in pain. A secondary outcome measure was the Global Perceived Effect scale (GPE). RESULTS: There was a statistically significant effect on the level of pain in the factor Period (T0-T1). However, there was no statistically significant difference with the passage of time between the groups (Group × Period) or in the factor Group. In the crossover group, 11 of 19 patients had a decrease in NRS of ≥ 2 at one month crossover (p = 0.65). There was no statistically significant difference in satisfaction with the passage of time between the groups (Group × Period). The independent factors Group and Period also showed no statistically significant difference. There was no statistically significant Group × Period effect for recovery, neither an effect of Group or of Period. CONCLUSION: The null hypothesis of no difference in the decrease in pain and in GPE between the treatment and sham groups cannot be rejected. Post hoc analysis revealed that the age of the patients and the severity of the initial pain significantly predicted a positive outcome. Cite this article: Bone Joint J 2016;98-B:1526-33.

To be in pain (or not): a computer enables outpatients to inform their physician.

BACKGROUND: In the outpatient oncology clinic, pain management is often inadequate. Incorporating a systematic pain management program into visits is likely to improve this. We implemented an integrated program, including a structured pain assessment, pain treatment protocol and patient education module. In the present study, we investigated whether this intervention improved pain control. PATIENTS AND METHODS: At seven oncology outpatient clinics, patients were asked to register their pain intensity on a touch screen computer. These scores were made available into their electronic medical records. Additionally, a hospital-wide treatment protocol for cancer-related pain and a patient education module were developed. A data warehouse system enabled us to extract patient data from the electronic medical record anonymously and to use them for analysis. The primary outcome of the study was the percentage of patients with moderate to severe pain [current pain (CPI), NRS > 4] measured during 2 weeks at the start and 6 months after implementation. As secondary outcomes, we studied the percentage of pain registrations in specific patient groups and the percentage of patients treated with a curative and a palliative intention with (moderate-severe) pain. Differences were tested with the χ(2) test. RESULTS: During the first 6 months, 3407 of the 4345 patients (78%) registered their pain intensity on the touch screen computer. The percentage of patients with moderate to severe CPI decreased 32% (P = 0.021): from 12.5% at start to 8.5% after 6 months. More patients in the palliative phase than in the curative phase of their disease registered their pain intensity (82% versus 75%, respectively, P < 0.005), and more patients in the palliative phase experienced moderate to severe pain (23% versus 14%, respectively, P < 0.001). CONCLUSION: Pain registration by patients themselves is feasible, provides insight into patients' pain intensity and may improve pain control in outpatients with cancer-related pain. CLINICAL TRIAL NUMBER: Because this is an innovation project and not a primary research project, it has no clinical trial number. The protocol and all materials involved were approved by the Institutional Review Board of the Erasmus MC (MEC-2009-324).

Reproducibility of axon reflex-related vasodilation assessed by dynamic thermal imaging in healthy subjects.

INTRODUCTION: Small nerve fiber dysfunction is an early feature of diabetic neuropathy. There is a strong clinical need for a non-invasive method to assess small nerve fiber function. Small nerve fibers mediate axon reflex-related vasodilation and play an important role in thermoregulation. Assessing the reflex vasodilation after local heating might elucidate some aspects of small fiber functioning. In this study, we determined the reproducibility of the reflex vasodilation after short local heating in healthy subjects, assessed with thermal imaging and laser Doppler imaging. METHODS: Healthy subjects underwent six heating rounds in one session (protocol I, N=10) or spread over two visits (protocol II, N=20). Reflex vasodilation was elicited by heating the skin to 42°C with an infrared lamp. Skin temperature and skin blood flow were recorded during heating and recovery with a thermal imaging camera and a laser Doppler imager. Skin temperature curves were fitted with a mathematical model to describe the heating and recovery phase with time constant tau (tauHeat and tauCool1). RESULTS: The reproducibility of tau within a session was moderate to excellent (intra-class correlation coefficient 0.42-0.86) and good (0.71-0.72) between different sessions. Within one session the differences in tauHeat were small (bias±SD -1.3±18.9s); the bias between two visits was -1.2±12.2s. For tauCool1 the differences were also small, 1.4±6.6s within a session and between visits -1.4±11.6s. CONCLUSIONS: The heat induced axon reflex-related vasodilation, assessed with thermal imaging and laser Doppler imaging, was reproducible both within a session and between different sessions. Tau describes the temporal profile in one parameter and represents the effects of all changes including blood flow and as such, is an indicator of the vasodilator function. TauHeat and tauCool1 can accurately describe the dynamics of the axon reflex-related vasodilator response in the heating and recovery phase respectively.

Structural Brain Alterations in Community Dwelling Individuals with Chronic Joint Pain.

BACKGROUND AND PURPOSE: Central sensitization in chronic pain involves structural brain changes that influence vulnerability to pain. Identifying brain regions involved in pain processing and sensitization can provide more insight into chronic pain. This study examines structural brain changes in chronic pain and experimental pain in a large population-based study. MATERIALS AND METHODS: For 3892 participants in the Rotterdam study, global and regional MR imaging brain volumes were automatically segmented and quantified. Chronic joint pain was defined as pain for more than half of all days during the past 6 weeks. Heat pain thresholds were measured in a subset of 1538 individuals. The association between the presence of chronic joint pain and global and lobar brain volumes was studied. Subsequently, literature was reviewed and the association of chronic pain and heat pain thresholds with 11 brain regions associated with musculoskeletal pain in previous publications was studied. RESULTS: Total gray matter volume was smaller in women with chronic pain (ß = -0.066, P = .016). This effect was primarily driven by lower gray matter volume in the temporal lobe (ß = 0.086, P = .005), the frontal lobe (ß = -0.060, P = .039), and the hippocampus (ß = -0.099, P = .002). In addition, we observed that a lower heat pain threshold was associated with smaller volumes of the hippocampus (ß = 0.017, P = .048), the thalamus (ß = 0.018, P = .009), and the anterior cingulate cortex (ß = -0.016, P = .037). In men, no significant associations were observed. CONCLUSIONS: The primary identified brain areas, the temporal and frontal lobes and the hippocampus, indicated involvement of emotional processing. The volumetric differences found indicated a sex-specific neuroplasticity in chronic pain. These results emphasized sex-specific and multidisciplinary pain treatment.

Comparison of tonic spinal cord stimulation, high-frequency and burst stimulation in patients with complex regional pain syndrome: a double-blind, randomised placebo controlled trial.

BACKGROUND: Complex Regional Pain Syndrome (CRPS) is a disabling disease that is sometimes difficult to treat. Although spinal cord stimulation (SCS) can reduce pain in most patients with CRPS, some do not achieve the desired reduction in pain. Moreover, the pain reduction can diminish over time even after an initially successful period of SCS. Pain reduction can be regained by increasing the SCS frequency, but this has not been investigated in a prospective trial. This study compares pain reduction using five SCS frequencies (standard 40 Hz, 500 Hz, 1200 Hz, burst and placebo stimulation) in patients with CRPS to determine which of the modalities is most effective. DESIGN: All patients with a confirmed CRPS diagnosis that have unsuccessfully tried all other therapies and are eligible for SCS, can enroll in this trial (primary implantation group). CRPS patients that already receive SCS therapy, or those previously treated with SCS but with loss of therapeutic effect over time, can also participate (re-implantation group). Once all inclusion criteria are met and written informed consent obtained, patients will undergo a baseline assessment (T0). A 2-week trial with SCS is performed and, if successful, a rechargeable internal pulse generator (IPG) is implanted. For the following 3 months the patient will have standard 40 Hz stimulation therapy before a follow-up assessment (T1) is performed. Those who have completed the T1 assessment will enroll in a 10-week crossover period in which the five SCS frequencies are tested in five periods, each frequency lasting for 2 weeks. At the end of the crossover period, the patient will choose which frequency is to be used for stimulation for an additional 3 months, until the T2 assessment. DISCUSSION: Currently no trials are available that systematically investigate the importance of variation in frequency during SCS in patients with CRPS. Data from this trial will provide better insight as to whether SCS with a higher frequency, or with burst stimulation, results in more effective pain relief. TRIAL REGISTRATION: Current Controlled Trials ISRCTN36655259.

Inflammation in cold complex regional pain syndrome.

BACKGROUND: In patients with complex regional pain syndrome (CRPS), the temperature of the affected side often differs from that of the contralateral side. In the acute phase, the affected side is usually warmer than the contralateral side, the so-called 'warm' CRPS. This thermal asymmetry can develop into a colder affected side, the so-called 'cold' CRPS. In contrast to cold CRPS, in warm CRPS, inflammation is generally assumed to be present. However, there are reports of cold CRPS patients, successfully treated with vasodilatation therapy, who subsequently displayed warm CRPS. It seems that inflammation could be 'hidden' behind vasomotor disturbance. This study was designed to test this hypothesis. METHODS: A retrospective analysis was made of patients in our CRPS database. We defined three types of CRPS: cold CRPS, neither cold nor warm (intermediate) CRPS, and warm CRPS. Of these patients, the difference between the level of the pro-inflammatory cytokines interleukin (IL)-6 (Δ IL-6) and tumor necrosis factor (TNF)-α (Δ TNF-α) in the affected extremity and that in the contralateral extremity was determined. RESULTS: The bilateral difference of the level of these cytokines did not differ among patients with cold CRPS, intermediate CRPS, or those with warm CRPS. CONCLUSION: Inflammation may be involved in cold CRPS.

Patient preference with respect to QoL and reduction in opioid-induced constipation (OIC) after treatment with prolonged-release (PR) oxycodone/naloxone compared with previous analgesic therapy [PREFER study].

OBJECTIVE: The aim of this study was to assess patient preference in terms of quality of life (QoL), analgesia and bowel function for patients with moderate to severe chronic non-malignant pain, when treated with oxycodone PR/naloxone PR compared with the previous WHO-step I and/or WHO-step II analgesic treatment . STUDY DESIGN: This was a 3-week open-label phase 3b study conducted in Belgium and the Netherlands, after 3 weeks patients could enter an extension phase. Patient preference with respect to QoL for oxycodone PR/naloxone PR treatment compared with previous WHO-step I and/or WHO-step II analgesics was assessed. A patient was considered a responder with respect to QoL if this assessment was 'better' or 'much better' compared with previous WHO-step I or II analgesics at any time point. RESULTS: Response rate with respect to QoL was 59.2% (95% CI: 51.7-66.8%) for the Full Analysis (FA)-population, for the Per Protocol-population response rate was 71.7% (95% CI: 63.1-80.3%). Explorative analysis showed that response rate with respect to QoL was highest in constipated patients pretreated with WHO-step II analgesics (73.8%). Mean ± SD pain score in the FA-population at start was 74.7 ± 16.6 decreasing to 53.9 ± 24.3 after a median (range) treatment period of 173.5 (31-771) days. For constipated subjects the significant reduction in constipation [improvement of the Bowel Function Index (BFI)], was -24.8 points (95% CI: -17.1 to -32.5). BFI for non-constipated subjects remained well below 28.8. Adverse events with oxycodone PR/naloxone PR treatment were well-known opioid-related adverse events. CONCLUSION: This study shows that the studied patients previously treated with WHO-step I and/or WHO-step II analgesics prefer treatment with oxycodone PR/naloxone PR with respect to QoL. Moreover, the study shows that treatment with oxycodone PR/naloxone PR significantly reduces OIC in constipated patients and that non-constipated patients do not develop OIC during treatment with oxycodone PR/naloxone PR.

Complex regional pain syndrome type I of the knee: a systematic literature review.

In our Center for Pain Medicine, a group of patients reported to have symptoms possibly attributable to complex regional pain syndrome (CRPS) of only the knee(s). Therefore, this study aimed to investigate whether the literature reports on patients with CRPS type I in the knee(s) alone and, if so, to summarize the reported diagnostics, aetiology and treatment strategies of CRPS of the knee(s). Medline, Embase, Cochrane Library, PubMed and Web of Science were searched for articles focusing on a painful disorder of the knee, most likely CRPS type I. Screening on title and abstract was followed by full-text reading and searching of reference lists to determine the final set of relevant articles. Of the 513 articles identified, 31 met the inclusion criteria. These articles reported on a total of 368 patients diagnosed with CRPS of the knee(s) based on the diagnostic criteria used at the time of publication. Knee surgery, especially arthroscopic surgery, was the most common inciting event in developing CRPS of the knee(s). Various treatment strategies were applied with variable outcomes. In conclusion, the scientific literature does report cases of CRPS type I of only the knee(s). This applies when using the diagnostic criteria prevailing at the time of publication and, obviously for a smaller number of cases, also when using the current Budapest criteria set. Arthroscopic knee surgery is described multiple times as the inciting event. We recommend to include CRPS of the knee in future research on the aetiological mechanisms of and optimal treatment for CRPS.

Pulse transit time as a quick predictor of a successful axillary brachial plexus block.

BACKGROUND: It can take up to 30 min to determine whether or not axillary block has been successful. Pulse transit time (PTT) is the time between the R-wave on electrocardiography (ECG) and the arrival of the resulting pressure pulse wave in the fingertip measured with photoplethysmography. It provides information about arterial resistance. Axillary block affects vasomotor tone causing loss of sympathetic vasoconstriction resulting in an increased PTT. Early objective assessment of a block can improve efficacy of operating room time and minimize patient's fear of possible conversion to general anesthesia. This study explores whether PTT can objectively, reliably and quickly predict a successful axillary block. METHODS: Forty patients undergoing hand surgery under axillary block were included. A three-lead ECG and photoplethysmographic sensors were placed on both index fingers. Measurements were made from 2 min before until 30 min after induction of the block or less if the patient was transferred for operation. Afterwards, PTT was calculated as the time between the R-wave on ECG and a reference point on the photoplethysmogram. To assess the change in PTT caused by the block, the PTT difference between the control and blocked arm was calculated. Sensitivity and specificity of PTT difference were calculated using receiver operating characteristic analysis. RESULTS: In a successful block, the mean PTT difference significantly increased after 3 min by 12 (standard error of the mean 3.9) ms, sensitivity 87% and specificity 71% (area under the curve 0.87, P = 0.004). CONCLUSIONS: PTT is a reliable, quick and objective method to assess whether axillary block is going to be successful or not.