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Tissue hypoxia in complex regional pain syndrome

M Koban, S Leis, S Schultze-Mosgau, F Birklein
2003 Pain  
., 2001) , sympathetic failure including sudomotor (Birklein et al., 1997) and vasomotor disturbances (Kurvers et al., 1995) as well as distal limb edema are essential for diagnosing CRPS (Birklein  ...  0:17, ns; affected side, F ¼ 1:94, ns).  ... 
doi:10.1016/s0304-3959(02)00484-0 pmid:12855324 fatcat:ajletm3mb5eunnzkkju2osnc6q

Thermal Thresholds Predict Painfulness of Diabetic Neuropathies

H. H. Kramer, R. Rolke, A. Bickel, F. Birklein
2004 Diabetes Care  
OBJECTIVE -Pathophysiology explaining pain in diabetic neuropathy (DN) is still unknown. RESEARCH DESIGN AND METHODS -Thirty patients with peripheral DN (17 men and 13 women; mean age 52.4 Ϯ 2.5 years) were investigated. Fifteen patients had neuropathic pain, and 15 patients were free of pain. Patients were followed over 2 years and examined at the beginning and thereafter every 6 months. Clinical severity and painfulness of the DN were assessed by the neuropathy impairment score and visual
more » ... og scales (VASs). Cold and warm perception thresholds as well as heat pain thresholds were obtained for evaluation of A␦-and C-fibers. Nerve conduction velocities (NCVs) and vibratory thresholds were recorded for analysis of thickly myelinated fibers. Moreover, for assessment of cardiac vagal function, heart rate variability (HRV) was evaluated. In order to reduce day-to-day variability of pain, mean values of the five time points over 2 years were calculated and used for further analysis. Data were compared with an age-and sex-matched control group of healthy volunteers. RESULTS -There were significant differences regarding electrophysiological studies, HRV and quantitative sensory testing (QST) between patients and healthy control subjects (P Ͻ 0.001). Generally, patients with neuropathic pain were indistinguishable from pain-free patients. In the pain group, however, VAS pain ratings were correlated to the impairment of small-fiber function (cold detection thresholds, P ϭ 0.02; warm detection thresholds, P ϭ 0.056). CONCLUSIONS -Intensity of pain in painful DN seems to depend on small nerve fiber damage and deafferentation. Abbreviations: CAN, cardiac autonomic neuropathy; DN, diabetic neuropathy; dSFN, diabetic smallfiber sensory neuropathy; HRV, heart rate variability; NCV, nerve conduction velocity; QST, quantitative sensory testing; VAS, visual analog scale; VT, vibratory threshold. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
doi:10.2337/diacare.27.10.2386 pmid:15451905 fatcat:3ilejf54k5fyppzk3mqfjsyybq

Sensitized peripheral nociception in experimental diabetes of the rat

D. Fuchs, F. Birklein, P. W. Reeh, S. K. Sauer
2010 Pain  
Painful neuropathy is a common complication of diabetes. Particularly in the early stage of diabetic neuropathy, patients are characterized by burning feet, hyperalgesia to heat, and mechanical stimuli, as if residual nociceptors were sensitized. Such symptoms are barely explained by common pathophysiological concepts of diabetic neuropathy. Diabetes was induced in Wistar rats by streptozotocin (STZ). After 4 weeks behavioral testing (Plantar test, Randall-Selitto) was conducted. Basal and
more » ... lated release of calcitonin gene-related peptide (CGRP), Substance P (SP) and prostaglandin E(2) (PGE(2)) from isolated skin and sciatic nerve were assessed by enzyme immunoassays. Electrophysiological properties of identified nociceptors under hyperglycemic, hypoxic, and acidotic conditions were investigated using the skin-nerve preparation. The diabetic rats showed hyperalgesia to heat and pressure stimulation. The basal CGRP/SP release was reduced, but chemical stimulation with bradykinin induced greater release of SP, CGRP and PGE(2) than in control animals. In contrast, capsaicin-stimulated CGRP release was reduced in sciatic nerves. Hypoxia per se lowered von Frey thresholds of most C-nociceptors to half. Hyperglycemic hypoxia induced ongoing discharge in all diabetic but not control C-fibers which was further enhanced under acidosis. Sensory and neurosecretory nociceptor functions are sensitized in diabetes. Diabetic C-fibers show exaggerated sensitivity to hyperglycemic hypoxia with and without additional acidosis, conditions that are thought to mimic ischemic episodes in diabetic nerves. Ongoing C-fiber discharge is known to induce spinal sensitization. Together with altered receptor and ion channel expressions this may contribute to painful episodes in diabetic neuropathy.
doi:10.1016/j.pain.2010.08.010 pmid:20832942 fatcat:u73svncz4nfd7jzwjsv5gaaht4

Electrically Stimulated Axon Reflexes Are Diminished in Diabetic Small Fiber Neuropathies

H. H. Kramer, M. Schmelz, F. Birklein, A. Bickel
2004 Diabetes  
TABLE 1 1 Continued SFN 7 SFN 8 SFN 9 SFN 10 SFN 11 SFN 12 NO-N 1 NO-N 2 NO-N 3 NO-N 4 NO-N 5 F/65 M/61 M/26 F/46 F/38 M/52 F/26 F/27 F/25 M/67 F DIABETES, VOL. 53, MARCH 2004  ...  TABLE 1 1 Biographical and clinical data of included patients SFN 1 SFN 2 SFN 3 SFN 4 SFN 5 SFN 6 Sex (M/F)/age (years) M/50 M/40 F/38 M/47 M/55 F/34 Diabetes type 2 1 1 2 2 1 Duration  ... 
doi:10.2337/diabetes.53.3.769 pmid:14988263 fatcat:wcfpeutg7rf5nb2gksijiegklq

Autoimmunity in Complex-Regional Pain Syndrome

F. BLAES, M. TSCHERNATSCH, M. E. BRAEU, O. MATZ, K. SCHMITZ, D. NASCIMENTO, M. KAPS, F. BIRKLEIN
2007 Annals of the New York Academy of Sciences  
Complex regional pain syndrome (CRPS) is an etiologically unclear syndrome with the main symptoms being pain, trophic and autonomic disturbances, and functional impairment that develops after limb trauma or operation and is located at the distal site of the affected limb. Because autoantibodies against nervous system structures have been described in these patients, an autoimmune etiology of CRPS is discussed. These autoantibodies bind to the surface of peripheral autonomic neurons. Using a
more » ... etitive binding assay, it can be shown that at least some of the CRPS sera bind to the same neuronal epitope. Autoimmune etiology of CRPS is a new pathophysiological concept and may have severe impact on the treatment of this often chronic disease.
doi:10.1196/annals.1381.018 pmid:17804544 fatcat:avgiomzi3jdq5plussyehxo3u4

Mislocalization of tactile stimulation in patients with complex regional pain syndrome

Ch. Maihöfner, B. Neundörfer, F. Birklein, H. O. Handwerker
2006 Journal of Neurology  
doi:10.1007/s00415-006-0117-z pmid:16705476 fatcat:j4rqav4yojbaho5dj2vas53k34

The motor system shows adaptive changes in complex regional pain syndrome

C. Maihofner, R. Baron, R. DeCol, A. Binder, F. Birklein, G. Deuschl, H. O. Handwerker, J. Schattschneider
2007 Brain  
., 1995; Birklein et al., 2000) . CRPS is characterized by autonomic, sensory and motor symptoms.  ...  Kinematic analysis One-way ANOVA demonstrated significant differences in total movement time between the groups [F(3,40) ¼ 5.8].  ... 
doi:10.1093/brain/awm131 pmid:17575278 fatcat:nnwldejat5csfmdeaxpr5obsmu

Patterns of Sympathetic Responses Induced by Different Stress Tasks

M. Fechir, T. Schlereth, T. Purat, S. Kritzmann, C. Geber, T. Eberle, M. Gamer, F. Birklein
2008 Open Neurology Journal  
Stress tasks are used to induce sympathetic nervous system (SNS) arousal. However, the efficacy and the patterns of SNS activation have not been systematically compared between different tasks. Therefore, we analyzed SNS activation during the following stress tasks: Presentation of negative, positive, and - as a control - neutral affective pictures, Color-Word interference test (CWT), mental arithmetic under time limit, singing a song aloud, and giving a spontaneous talk. We examined 11 healthy
more » ... subjects and recorded the following SNS parameters: Activation of emotional sweating by quantitative sudometry, skin vasoconstriction by laser-Doppler flowmetry, heart rate by ECG, blood pressure by determination of pulse wave transit time (PWTT), and electromyographic (EMG) activity of the trapezius muscle. Moreover, subjective stress ratings were acquired for each task using a visual analog scale. All tasks were felt significantly stressful when compared to viewing neutral pictures. However, SNS activation was not reliable: Affective pictures did not induce a significant SNS response; singing, giving a talk and mental arithmetic selectively increased heart rate and emotional sweating. Only the CWT globally activated the SNS. Regarding all tasks, induction of emotional sweating, increase of heart rate and blood pressure significantly correlated with subjective stress ratings, in contrast to EMG and skin vasoconstriction.Our results show that the activation of the SNS widely varies depending on the stress task. Different stress tasks differently activate the SNS, which is an important finding when considering sympathetic reactions - in clinical situations and in research.
doi:10.2174/1874205x00802010025 pmid:19018304 pmcid:PMC2577930 fatcat:nskxjreo6rg7dlkkzqcv7qhcp4

Anatomical Correlate of Impaired Covert Visual Attentional Processes in Patients with Cerebellar Lesions

B. Baier, M. Dieterich, P. Stoeter, F. Birklein, N. G. Muller
2010 Journal of Neuroscience  
., main effects of validity (F (1,24) ϭ 5.86; p Ͻ 0.023), latency (F (3,72) ϭ 5.71; p ϭ 0.001), and group (F (1,24) ϭ 42.61; p Ͻ 0.01), indicating that assignment to the normal RT group, valid trials,  ...  Presentation side had no significant effect (F (1,38) ϭ 1.37; p ϭ 0.251).  ... 
doi:10.1523/jneurosci.0487-09.2010 pmid:20220011 fatcat:yldernxe5fc4zco5gqcenrb3ry

Activation of Cutaneous Immune Responses in Complex Regional Pain Syndrome

Frank Birklein, Peter D. Drummond, Wenwu Li, Tanja Schlereth, Nahid Albrecht, Philip M. Finch, Linda F. Dawson, J. David Clark, Wade S. Kingery
2014 Journal of Pain  
The pathogenesis of complex regional pain syndrome (CRPS) is unresolved, but tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) are elevated in experimental skin blister fluid from CRPS-affected limbs, as is tryptase, a marker for mast cells. In the rat fracture model of CRPS, exaggerated sensory and sympathetic neural signaling stimulate keratinocyte and mast cell proliferation, causing the local production of high levels of inflammatory cytokines leading to pain behavior. The
more » ... investigation used CRPS patient skin biopsies to determine whether keratinocyte and mast cell proliferation occur in CRPS skin and to identify the cellular source of the up-regulated TNF-α, IL-6, and tryptase observed in CRPS experimental skin blister fluid. Skin biopsies were collected from the affected skin and the contralateral mirror site in 55 CRPS patients and the biopsy sections were immunostained for keratinocyte, cell proliferation, mast cell markers, TNF-α, and IL-6. In early CRPS, keratinocytes were activated in the affected skin, resulting in proliferation, epidermal thickening, and up-regulated TNF-α and IL-6 expression. In chronic CRPS, there was reduced keratinocyte proliferation, leading to epidermal thinning in the affected skin. Acute CRPS patients also had increased mast cell accumulation in the affected skin, but there was no increase in mast cell numbers in chronic CRPS.
doi:10.1016/j.jpain.2014.01.490 pmid:24462502 pmcid:PMC4011956 fatcat:wipicp35ora2xdydkzp3mbvney

Evaluation of the Autonomic Nervous System Using the FAN® Device - Range of Normal and Examples of Abnormal

S. Haegele-Link, D. Claus, S. Ducker, T. Vogt, F. Birklein
2008 Open Neurology Journal  
ns), nor height (F=0.02, ns) nor weight (F=0.98, ns) .  ...  Just two parameters, the coefficient of variation during deep respiration (F=4.703, p<0.04) and the coefficient of variation at rest (F=4.128, p<0.05), were reduced.  ... 
doi:10.2174/1874205x00802010012 pmid:19018302 pmcid:PMC2577935 fatcat:a3x7yyavqbg6zp3fuuhokekzpa

Insular Cortex Activity Is Associated with Effects of Negative Expectation on Nociceptive Long-Term Habituation

R. Rodriguez-Raecke, B. Doganci, M. Breimhorst, A. Stankewitz, C. Buchel, F. Birklein, A. May
2010 Journal of Neuroscience  
A significant time ϫ context interaction revealed differences in the time course of pain ratings with respect to the context group (F (8,296) ϭ 2.67, p ϭ 0.043).  ...  No significant interaction with context was observed (F (8,296) ϭ 1.05, p ϭ 0.401) pointing at a similar increase of pain threshold over time from day 1 to day 90 (Fig. 1) .  ... 
doi:10.1523/jneurosci.2197-10.2010 pmid:20739557 pmcid:PMC6633339 fatcat:vyz2muyd6bhibgxjjpiy7xl3hu

Keeping Memory Clear and Stable--The Contribution of Human Basal Ganglia and Prefrontal Cortex to Working Memory

B. Baier, H.-O. Karnath, M. Dieterich, F. Birklein, C. Heinze, N. G. Muller
2010 Journal of Neuroscience  
Right-sided lesions Left-sided lesions Number 31 30 Sex 17 f; 14 m 10 f; 20 m Etiology 31 infarcts 29 infarcts, 1 bleeding Age (years) ͓median (range)͔ 68 (20 -84) 68 (32-85) Time interval  ...  Accordingly, the repeatedmeasurement ANOVA revealed a main effect for the factor task (three levels) (F (1,60) ϭ 56.263; p ϭ 0.001).  ... 
doi:10.1523/jneurosci.1513-10.2010 pmid:20660261 pmcid:PMC6632833 fatcat:5ev5fhfzy5fzzdqeoqoxwmhq4e

Are you better? A multi-centre study of patient-defined recovery from Complex Regional Pain Syndrome

A. Llewellyn, C.S. McCabe, Y. Hibberd, P. White, L. Davies, J. Marinus, R.G.S.M. Perez, I. Thomassen, F. Brunner, C. Sontheim, F. Birklein, T. Schlereth (+11 others)
2017 European Journal of Pain  
., 1995; Birklein and Schlereth, 2015) .  ...  1 or Type 2, confirmed by clinical records) (Harden et al., 2010) were identified from eight country-specific CRPS databases or clinic-specific research lists: UK (Bath), Germany (Mainz; Erlangen, F€  ... 
doi:10.1002/ejp.1138 pmid:29194871 fatcat:eq4ehhatsbg57iuqb3uh6qaydm

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

KD Bharwani, AB Kersten, Amanda Stone, F Birklein, S Bruehl, Maaike Dirckx, PD Drummond, Janne Gierthmühlen, A Goebel, L Knudsen, FJPM Huygen
2021 Journal of Pain Research  
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. A systematic search was conducted in MEDLINE, EMBASE and Cochrane
more » ... L 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. 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. 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.
doi:10.2147/jpr.s326638 pmid:34737631 pmcid:PMC8558034 fatcat:ssidcueyjnahbeo3ugwbqsotgu
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