Pulse transit time as a proxy for vasoconstriction in younger and older adults.

OBJECTIVES: Changes of vasoconstriction may be measured non-invasively using pulse transit time. This study assessed the sensitivity, test-retest reliability and validity of pulse transit time during vasoconstriction provocation and active standing, and the predictive value of pulse transit time for blood pressure drop. METHODS: Fifty-five younger (age < 65 years) and 31 older adults (age > 70 years) underwent electrocardiography, wrist and finger photoplethysmography and continuous blood pressure and total peripheral resistance measurements during vasoconstriction provocation using a cold pressor test (21 younger adults), or active stand tests (all other participants). Pulse transit time was defined as the time lag between the electrocardiography R-peak and the peak in the photoplethysmography first derivative; sensitivity as a significant decrease relative to baseline; test-retest reliability as the intra class correlation between different repeats of the same test; validity as the association between peripheral resistance and pulse transit time; predictive value as the association between supine resting pulse transit time and mean arterial pressure drop during active standing. RESULTS: Finger pulse transit time was sensitive and reliable (ICC 0.2-0.8) during vasoconstriction provocation, but wrist pulse transit time was poorly reliable (ICC 0-0.5); only finger pulse transit time was sensitive to and reliable (ICC 0.4-0.8) during active standing in both younger and older adults. Finger pulse transit time was not associated with total peripheral resistance. Supine resting pulse transit time had predictive value for blood pressure drop during active standing in older adults (ß -0.16; p 0.025). CONCLUSIONS: Pulse transit time was sensitive to and reliable during vasoconstriction provocation and active standing, but did not significantly differ between younger and older adults. Pulse transit time could not be demonstrated to particularly reflect vasoconstriction, but it had predictive value for blood pressure drop during active standing.

Comparison between pulse wave velocities measured using Complior and measured using Biopac.

Arterial stiffness is a reliable prognostic parameter for cardiovascular diseases. The effect of change in arterial stiffness can be measured by the change of the pulse wave velocity (PWV). The Complior system is widely used to measure PWV between the carotid and radial arteries by means of piezoelectric clips placed around the neck and the wrist. The Biopac system is an easier to use alternative that uses ECG and simple optical sensors to measure the PWV between the heart and the fingertips, and thus extends a bit more to the peripheral vasculature compared to the Complior system. The goal of this study was to test under various conditions to what extent these systems provide comparable and correlating values. 25 Healthy volunteers, 20-30 years old, were measured in four sequential position: sitting, lying, standing and sitting. The results showed that the Biopac system measured consistently and significantly lower PWV values than the Complior system, for all positions. Correlation values and Bland-Altman plots showed that despite the difference in PWV magnitudes obtained by the two systems the measurements did agree well. Which implies that as long as the differences in PWV magnitudes are taken into account, either system could be used to measure PWV changes over time. However, when basing diagnosis on absolute PWV values, one should be very much aware of how the PWV was measured and with what system.

Small intra-individual variability of the pre-ejection period justifies the use of pulse transit time as approximation of the vascular transit.

BACKGROUND: Vascular transit time (VTT) is the propagation time of a pulse wave through an artery; it is a measure for arterial stiffness. Because reliable non-invasive VTT measurements are difficult, as an alternative we measure pulse transit time (PTT). PTT is defined as the time between the R-wave on electrocardiogram and arrival of the resulting pulse wave in a distal location measured with photoplethysmography (PPG). The time between electrical activation of the ventricles and the resulting pulse wave after opening of the aortic valve is called the pre-ejection period (PEP), a component of PTT. The aim of this study was to estimate the variability of PEP at rest, to establish how accurate PTT is as approximation of VTT. METHODS: PTT was measured and PEP was assessed with echocardiography (gold standard) in three groups of 20 volunteers: 1) a control group without cardiovascular disease aged <50 years and 2) aged >50 years, and 3) a group with cardiovascular risk factors, defined as arterial hypertension, dyslipidemia, kidney failure and diabetes mellitus. RESULTS: Per group, the mean PEP was: 1) 58.5 ± 13.0 ms, 2) 52.4 ± 11.9 ms, and 3) 57.6 ± 11.6 ms. However, per individual the standard deviation was much smaller, i.e. 1) 2.0-5.9 ms, 2) 2.8-5.1 ms, and 3) 1.6-12.0 ms, respectively. There was no significant difference in the mean PEP of the 3 groups (p = 0.236). CONCLUSION: In conclusion, the intra-individual variability of PEP is small. A change in PTT in a person at rest is most probably the result of a change in VTT rather than of PEP. Thus, PTT at rest is an easy, non-invasive and accurate approximation of VTT for monitoring arterial stiffness.

Increasing accuracy of pulse transit time measurements by automated elimination of distorted photoplethysmography waves.

Photoplethysmography (PPG) is a widely available non-invasive optical technique to visualize pressure pulse waves (PWs). Pulse transit time (PTT) is a physiological parameter that is often derived from calculations on ECG and PPG signals and is based on tightly defined characteristics of the PW shape. PPG signals are sensitive to artefacts. Coughing or movement of the subject can affect PW shapes that much that the PWs become unsuitable for further analysis. The aim of this study was to develop an algorithm that automatically and objectively eliminates unsuitable PWs. In order to develop a proper algorithm for eliminating unsuitable PWs, a literature study was conducted. Next, a '7Step PW-Filter' algorithm was developed that applies seven criteria to determine whether a PW matches the characteristics required to allow PTT calculation. To validate whether the '7Step PW-Filter' eliminates only and all unsuitable PWs, its elimination results were compared to the outcome of manual elimination of unsuitable PWs. The '7Step PW-Filter' had a sensitivity of 96.3% and a specificity of 99.3%. The overall accuracy of the '7Step PW-Filter' for detection of unsuitable PWs was 99.3%. Compared to manual elimination, using the '7Step PW-Filter' reduces PW elimination times from hours to minutes and helps to increase the validity, reliability and reproducibility of PTT data.

Pathophysiological Mechanisms Involved in Vasomotor Disturbances in Complex Regional Pain Syndrome and Implications for Therapy: A Review.

Complex regional pain syndrome (CRPS) is characterized by continuous pain, disproportional to the initial trauma. It usually spreads to the distal parts of the affected limb. Besides continuing pain, a mix of sensory, sudo- and vasomotor disturbances, motor dysfunction, and trophic changes is responsible for physical complaints. Vasomotor disturbance is characterized by changes in skin temperature and color. In CRPS patients with a cold extremity, a decrease in blood flow can cause decreased tissue saturation and tissue acidosis, resulting in ischemic pain. The pathophysiology of vasomotor disturbances is not completely understood. Temperature asymmetry is generally assumed as a result of disturbance in the sympathetic nervous system. Vasodilating drugs and sympathetic blockade have been cornerstones of therapy in cold CRPS for years. However, only a limited part of these patients improve on this kind of therapies. Research has shown a pivotal role for inflammation in the pathophysiology of CRPS. Inflammation can result in endothelial dysfunction. Endothelial function plays an important role in the local regulation of vascular tone. Endothelial dysfunction could be another mechanism responsible for the vasomotor disturbances in cold CRPS. An important goal in the treatment of cold-type CRPS is the restoration of a normal blood flow. Consequently it is important to distinguish the underlying pathophysiological mechanisms of vasomotor disturbances. A disturbance of the sympathetic nervous system may require another type of treatment than inflammation-induced endothelial dysfunction. Diagnostic tools to distinguish these underlying pathophysiological mechanisms of vasomotor disturbances would enable a mechanism-based treatment and improve clinical outcome.

Effect of heat-induced pain stimuli on pulse transit time and pulse wave amplitude in healthy volunteers.

Pain is commonly assessed subjectively by interpretations of patient behaviour and/or reports from patients. When this is impossible the availability of a quantitative objective pain assessment tool based on objective physiological parameters would greatly benefit clinical practice and research beside the standard self-report tests. Vasoconstriction is one of the physiological responses to pain. The aim of this study was to investigate whether pulse transit time (PTT) and pulse wave amplitude (PWA) decrease in response to this vasoconstriction when caused by heat-induced pain. The PTT and PWA were measured in healthy volunteers, on both index fingers using photoplethysmography and electrocardiography. Each subject received 3 heat-induced pain stimuli using a Temperature-Sensory Analyzer thermode block to apply a controlled, increasing temperature from 32.0 °C to 50.0 °C to the skin. After reaching 50.0 °C, the thermode was immediately cooled down to 32.0 °C. The study population was divided into 2 groups with a time-interval between the stimuli 20s or 60s. The results showed a significant (p < 0.05) decrease of both PTT and PWA on the stimulated and contralateral side. Moreover, there was no significant difference between the stimulated and contralateral side. The time-interval of 20s was too short to allow PTT and PWA to return to baseline values and should exceed 40s in future studies. Heat-induced pain causes a decrease of PTT and PWA. Consequently, it is expected that, in the future, PTT and PWA may be applied as objective indicators of pain, either beside the standard self-report test, or when self-report testing is impossible.

Diurnal and nocturnal skin temperature regulation in chronic complex regional pain syndrome.

UNLABELLED: Skin temperature changes due to vasomotor disturbances are important features of complex regional pain syndrome (CRPS). Because this phenomenon has only been studied under controlled conditions, information on daily circadian variability is lacking. Also, studies in chronic CRPS patients with abnormal posturing, in which coldness of the affected extremity is more common, do not exist. We examined the response to external heating as well as circadian temperature changes over several days in the affected legs of 14 chronic CRPS patients with abnormal posturing and 17 controls. Skin temperatures were recorded hourly for 14 days using wireless sensors. Although the patients' affected extremities were significantly colder before external heating, the vasodilatory response was similar in the 2 groups. Additionally, median skin temperature differences between both legs and their variability was larger in patients than in controls during the day, but not during the night. These findings indicate that the mechanisms underlying impaired skin circulation in CRPS during daytime are reversible under certain circumstances. The large variation in skin temperature differences during the day questions the validity of using a single measurement in the diagnosis of CRPS, and our results indicate that only temperature differences >1.0 °C should be considered to reflect vasomotor disturbances. PERSPECTIVE: This article shows that chronic CRPS patients have a normal vasodilatory response to external heating and that skin temperature differences between the affected and unaffected lower limbs, which were highly variable during daytime, disappeared during sleep. This indicates that part of the vasomotor regulation in these patients is still functional.

Technical and radiological image quality comparison of different liquid crystal displays for radiology.

BACKGROUND: To inform cost-effective decisions in purchasing new medical liquid crystal displays, we compared the image quality in displays made by three manufacturers. METHODS: We recruited 19 radiologists and residents to compare the image quality of four liquid crystal displays, including 3-megapixel Barco(®), Eizo(®), and NEC(®) displays and a 6-megapixel Barco display. The evaluators were blinded to the manufacturers' names. Technical assessments were based on acceptance criteria and test patterns proposed by the American Association of Physicists in Medicine. Radiological assessments were performed on images from the American Association of Physicists in Medicine Task Group 18. They included X-ray images of the thorax, knee, and breast, a computed tomographic image of the thorax, and a magnetic resonance image of the brain. Image quality was scored on an analog scale (range 0-10). Statistical analysis was performed with repeated-measures analysis of variance. RESULTS: The Barco 3-megapixel display passed all acceptance criteria. The Eizo and NEC displays passed the acceptance criteria, except for the darkest pixel value in the grayscale display function. The Barco 6-megapixel display failed criteria for the maximum luminance response and the veiling glare. Mean radiological assessment scores were 7.8±1.1 (Barco 3-megapixel), 7.8±1.2 (Eizo), 8.1±1.0 (NEC), and 8.1±1.0 (Barco 6-megapixel). No significant differences were found between displays. CONCLUSION: According to the tested criteria, all the displays had comparable image quality; however, there was a three-fold difference in price between the most and least expensive displays.

Rotterdam Advanced Multiple Plate: a novel method to measure cold hyperalgesia and allodynia in freely behaving rodents.

BACKGROUND: To investigate the pathophysiology of temperature hypersensitivity in neuropathic pain rodent models, it is essential to be able to quantify the phenotype as objective as possible. Current temperature sensitivity measuring paradigms are performed during exposure to external factors, i.e. light, sound and smell, which modulate behavior significantly. In addition the present outcome measure for temperature hypersensitivity in rodents is the examination of the hind paw lift upon exposure to a certain temperature, which reflects more a reflex-flexion than an experience of pain. NEW METHOD: Therefore the Rotterdam Advanced Multiple Plate (RAMP) was developed to assess cold hyperalgesia and allodynia objectively in freely behaving neuropathic pain rats, which measures the avoidance for certain temperatures and monitoring the location of the rat with an infrared camera while excluding external environmental influences such as light and sound. RESULTS: Compared to sham rats, the spared nerve injury (SNI) rats demonstrated a higher preference for the comfortable plate (27 °C) when the other three plates were set at 5 °C, 14 °C, 17 °C and 19 °C. We were unable to detect heat hyperalgesia and allodynia with the RAMP. COMPARISON WITH EXISTING METHOD: The paw withdrawal method displays similar results during cold hypersensitivity measurements as observed with the RAMP. The SNI group did display heat hypersensitivity during the paw withdrawal test. CONCLUSIONS: The results indicate that the RAMP is able to quantify cold hyperalgesia and allodynia in neuropathic pain rats while resolves some of the problems of conventional temperature sensitivity measuring paradigms in rodents.

Comparison of bilateral pulse arrival time before and after induced vasodilation by axillary block.

The propagation time of arterial pulse waves provides information about arterial stiffness. Pulse arrival time (PAT) is calculated as the time between the R-wave (ECG) and three reference points on photoplethysmographic (PPG) pulse waves: foot, first derivative and peak. Because large variation in PAT-values between patients exists, measurements of the contra-lateral arm as reference could be a solution. However, anatomical differences between arteries of the arms could introduce an offset of PAT. Furthermore, when arterial stiffness decreases (e.g. after axillary blockade (AxB)) and pulse wave amplitude increases (vasodilation), the pulse waveform can change. The aim of this study was to investigate whether there is a difference between the PAT of both arms and to evaluate the effect of vasodilation after AxB on PAT. ECG and PPG was measured on both hands in 34 patients, starting 2 min before the injection of local anaesthetic of an AxB and continuing for a period of 30 min after block placement. PAT of the baseline and after AxB were calculated and compared. The mean-PAT of both arms were not significantly different for the three reference points. After AxB, PAT significantly increased for all reference points. PAT can be used for intra-subject comparison.

Skin conductance peaks could result from changes in vital parameters unrelated to pain.

INTRODUCTION: Pain is usually assessed by the interpretation of behavior, which can be subjective. Therefore, there is an ongoing search for more objective methods. Performance of skin conductance measurement as a pain assessment tool is variable, as some studies report low specificity and a low predictive value of the method. The aim of this pilot study was to test whether autoregulation of the skin temperature influences the skin conductance of pain-free infants. RESULTS: Skin conductance was highly correlated with skin temperature in all subjects. Moreover, a significant change in all other vital parameters was observed on comparing before- and after-peak data. DISCUSSION: These results indicate that sympathetic neural activity to maintain homeostasis (such as autoregulation of skin temperature) results in skin conductance peaks. Real-time evaluation of the sympathetic nervous system would be valuable for pain assessment. However, the technique should be better defined to increase both sensitivity and specificity for the measurement of pain before use in daily practice can be advocated. METHODS: We included 11 infants, median (interquartile range (IQR)) age of 34 (13-76) d, who were admitted to the surgical high-care unit for monitoring after surgery. None was treated with opioids or sedatives, and observational pain scores were low.

Cold-induced vasodilatation following traumatic median or ulnar nerve injury.

PURPOSE: Peripheral nerve injury of the upper extremity frequently causes changes in the thermoregulatory system of the hands and fingers and leads to reports of cold intolerance. In this study, we aimed to measure the influence of median or ulnar nerve injury on cold-induced vasodilatation (CIVD) during prolonged cooling at low temperatures. METHODS: We tested 12 patients with a median (n = 6) or ulnar (n = 6) injury 4 to 76 months after nerve repair. The palmar sides of both hands were cooled continuously using a cold plate at 5°C. We measured the skin temperature of the fingers using videothermography and plotted graphs of the temperature changes of the nailbed. The presence of a CIVD reaction was defined as a minimum increase in temperature of 2.5°C starting at the distal phalanx. Furthermore, we measured self-reported symptoms of cold intolerance using the Cold Intolerance Severity Scale questionnaire. RESULTS: A CIVD reaction was absent in the affected digits of 4 patients (follow-up, 6-37 mo), whereas the CIVD reaction in the uninjured hand was present. The CIVD was present in 6 patients after 50 months' follow-up (range, 24-76 mo). Two patients had no CIVD reaction in the injured or uninjured fingers. All patients with a CIVD response had at least diminished protective sensation. Presence of the CIVD reaction did not exclude self-reported symptoms of cold intolerance. CONCLUSIONS: After peripheral nerve injury, it is possible to recover the CIVD reaction. This might be an indication of nerve recovery. However, a positive CIVD reaction does not exclude subjective symptoms of posttraumatic cold intolerance. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.

Rewarming patterns in hand fracture patients with and without cold intolerance.

PURPOSE: It is often assumed that cold intolerance is associated with abnormalities in the skin temperature due to changes in the blood flow of the hands. In this study, we determined whether patients with and without cold intolerance after a hand fracture or healthy controls have a diminished rewarming after a cold stimulus. METHODS: The severity of cold intolerance was evaluated using the Cold Intolerance Symptom Severity (CISS) questionnaire. To determine whether abnormal rewarming plays a major role in the underlying pathophysiology of cold intolerance, a cold-stress test was applied at a mean of 30 months (with a range of 11 mo) after the patients recovered from a hand fracture. A control group also underwent identical cold-stress testing for comparison. Temperature during the rewarming phase was measured using videothermography. RESULTS: Thirteen control subjects and 18 patients participated. Control subjects did not report any symptoms of cold intolerance (CISS score, 0) and no loss of sensibility was measured. The mean CISS score of all patients was 27.8; 9 patients scored above the cut-off value for normal cold intolerance. No significant differences were found in the rewarming patterns between (1) the affected and non-affected hand of the postfracture patients, (2) the dominant and non-dominant hand of the control subjects, and (3) the patients and controls. CONCLUSIONS: The results of this study revealed no relation between the severity of cold intolerance and rewarming patterns after cold stress testing. This might suggest that temperature regulation of the hands in post-fracture patients might not be responsible for the symptoms of cold intolerance, based on cold-stress test response.

Neural influence on cold induced vasodilatation using a new set-up for bilateral measurement in the rat hind limb.

Cold induced vasoconstriction (CIVC) is a way for mammals to reduce heat loss in an effort to maintain body core temperature. As blood flow to a cooled extremity is reduced, the amount of body heat lost at the cooled location is minimised. However, when the extremity temperature gets below a certain threshold, Cold induced vasodilatation (CIVD) occurs, a phenomenon that is believed to reduce the risk of local cold injuries. Many theories explaining the mechanism of the CIVD reaction have been postulated, but no consensus has been found. One of these theories is that the CIVD reaction is controlled neurally. To study the effect of neural influence on the vascularisation and rewarming patterns a new experimental set-up was designed. This set-up is able to measure responses in both hind paws simultaneously, creating the opportunity to study the effect of nerve injury on one limb and use the contralateral limb as a control. Ten rats received a sciatic nerve transection and repair of either the left (n=5) or the right (n=5) hind limb. Measurements were performed, 1 day pre-operatively, directly post-operatively, and at days 1, 7, 14, 21, 35 and 49 post-operatively. Although results are not significant, there is a tendency for the CIVD reaction to be reduced in the nerve injured paw until the nerve is regenerated around day 35. Further investigation of neural influence on the CIVD reaction will be necessary; this set-up may prove to be useful in future experiments to elucidate the mechanism of the CIVD reaction.

No recovery of cold complex regional pain syndrome after transdermal isosorbide dinitrate: a small controlled trial.

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.

Effect of tadalafil on blood flow, pain, and function in chronic cold complex regional pain syndrome: a randomized controlled trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Tadalafil may be a promising new treatment for patients that have chronic cold CRPS due to endothelial dysfunction, and deserves further investigation. TRIAL REGISTRATION: The registration number in the Dutch Trial Register is ISRCTN60226869.

Six years follow-up of the levels of TNF-alpha and IL-6 in patients with complex regional pain syndrome type 1.

In an earlier study, levels of the proinflammatory cytokines TNF-alpha and IL-6 are higher in blisters fluid from the complex regional pain syndrome type 1 (CRPS1) side obtained at 6 and 30 months (median) after the initial event. The aim of this follow-up study is to determine the involvement of these cytokines in long lasting CRPS1. Twelve CRPS1 patients, with median disease duration of 72 months, participated. The levels of TNF-alpha and IL-6 were measured in blister fluid; disease activity was reevaluated by measuring pain and differences in temperature, volume, and mobility between both extremities. Differences in levels of IL-6 and TNF-alpha and mobility between both sides were significantly decreased. Pain and differences in temperature and volume were not significantly altered. No correlation was found between the cytokines and the disease characteristics. These results indicate that IL-6 and TNF-alpha are only partially responsible for the signs and symptoms of CRPS1.

Using skin surface temperature to differentiate between complex regional pain syndrome type 1 patients after a fracture and control patients with various complaints after a fracture.

OBJECTIVE: In this study, we assessed the validity of skin surface temperature recordings, based on various calculation methods applied to the thermographic data, to diagnose acute complex regional pain syndrome type 1 (CRPS1) fracture patients. METHODS: Thermographic recordings of the palmar/plantar side and dorsal side of both hands or feet were made on CRPS1 patients and in control fracture patients with/without and without complaints similar to CRPS1 (total in the three subgroups = 120) just after removal of plaster. Various calculation methods applied to the thermographic data were compared using receiver operating characteristics analysis to obtain indicators of diagnostic value. RESULTS: There were no significant differences in demographic data and characteristics among the three subgroups. The most pronounced differences among the subgroups were vasomotor signs in the CRPS1 patients. The involved side in CRPS1 patients was often warmer compared with the noninvolved extremity. The difference in temperature between the involved site and the noninvolved extremity in CRPS1 patients significantly differed from the difference in temperature between the contralateral extremities of the two control groups. The largest temperature difference between extremities was found in CRPS1 patients. The difference in temperature recordings comparing the palmar/plantar and dorsal recording was not significant in any group. The sensitivity and specificity varied considerably between the various calculation methods used to calculate temperature difference between extremities. The highest level of sensitivity was 71% and the highest specificity was 64%; the highest positive predictive value reached a value of 35% and the highest negative predictive 84%, with a moderate 0.60 > or = area under the curve < or = 0.65. CONCLUSION: The validity of skin surface temperature recordings under resting conditions to discriminate between acute CRPS1 fracture patients and control fracture patients with/without complaints is limited, and only useful as a supplementary diagnostic tool.

Tumor necrosis factor-alpha and interleukin-6 are not correlated with the characteristics of Complex Regional Pain Syndrome type 1 in 66 patients.

It was previously shown in a group of 9 patients with complex regional pain syndrome type 1 (CRPS1) that levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are higher in blister fluid from the involved side. We hypothesize that local inflammation is responsible for the characteristics of CRPS1. The aim of this study was to confirm the previous observation in a large group of CRPS1 patients, repeating the measurement of TNF-alpha and IL-6 in blister fluid. Furthermore, we sought to determine whether these cytokines are responsible for the characteristics of CRPS1 and characterize the relationship between cytokine levels and duration of the disease. Sixty-six patients with CRPS1 participated. Skin blisters were artificially induced for measurement of cytokines in both extremities. The following disease characteristics were assessed: pain and differences in temperature, volume, and mobility between the extremities. TNF-alpha and IL-6 levels were significantly higher in blister fluid from the involved side. However, cytokine levels did not correlate with the characteristics or duration of the disease. Our findings confirm the presence of local inflammation in a population of 66 patients in the first 2 years of CRPS1. Proinflammatory cytokines seem to be only partly involved in the pathophysiology of CRPS1, as indicated by the lack of coherence between TNF-alpha and IL-6 levels and the signs and symptoms of inflammation and disease duration. Other inflammatory mediators and mechanisms, such as central sensitization, are probably involved in the early stages of CRPS1.