Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39
Filtrar
1.
J Neuroinflammation ; 15(1): 105, 2018 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-29642930

RESUMO

BACKGROUND: Both dysfunctional neuropeptide signaling and immune system activation are characteristic of complex regional pain syndrome (CRPS). Unknown is whether substance P (SP) or calcitonin gene-related peptide (CGRP) support autoantibody production and, consequently, nociceptive sensitization. METHODS: These experiments involved the use of a well-characterized tibia fracture model of CRPS. Mice deficient in SP expression (Tac1-/-) and CGRP signaling (RAMP1-/-) were used to probe the neuropeptide dependence of post-fracture sensitization and antibody production. The deposition of IgM in the spinal cord, sciatic nerves, and skin was followed using Western blotting, as was expression of the CRPS-related autoantigen cytokeratin 16 (Krt16). Passive serum transfer to B-cell-deficient muMT mice was used to assess the production of functional autoantibodies in CRPS model mice. The use of immunohistochemistry allowed us to assess neuropeptide-containing fiber distribution and Langerhans cell abundance in mouse and human CRPS patient skin, while Langerhans cell-deficient mice were used to assess the functional contributions of these cells. RESULTS: Functional SP and CGRP signaling were required both for the full development of nociceptive sensitization after fracture and the deposition of IgM in skin and neural tissues. Furthermore, the passive transfer of serum from wildtype but not neuropeptide-deficient mice to fractured muMT mice caused enhanced allodynia and postural unweighting. Langerhans cells were increased in number in the skin of fracture mice and CRPS patients, and those increases in mice were reduced in neuropeptide signaling-deficient animals. Unexpectedly, Langerhans cell-deficient mice showed normal nociceptive sensitization after fracture. However, the increased expression of Krt16 after tibia fracture was not seen in neuropeptide-deficient mice. CONCLUSIONS: Collectively, these data support the hypothesis that neuropeptide signaling in the fracture limb of mice is required for autoantigenic IgM production and nociceptive sensitization. The mechanism may be related to neuropeptide-supported autoantigen expression.


Assuntos
Imunidade Adaptativa/fisiologia , Síndromes da Dor Regional Complexa/imunologia , Síndromes da Dor Regional Complexa/metabolismo , Imunoglobulina M/metabolismo , Neuropeptídeos/imunologia , Neuropeptídeos/metabolismo , Adulto , Idoso de 80 Anos ou mais , Animais , Síndromes da Dor Regional Complexa/etiologia , Síndromes da Dor Regional Complexa/patologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/genética , Humanos , Células de Langerhans/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Precursores de Proteínas/deficiência , Precursores de Proteínas/genética , Proteína 1 Modificadora da Atividade de Receptores/deficiência , Proteína 1 Modificadora da Atividade de Receptores/genética , Pele/patologia , Taquicininas/deficiência , Taquicininas/genética , Fraturas da Tíbia/complicações
2.
Expert Rev Proteomics ; 14(10): 857-867, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28803495

RESUMO

INTRODUCTION: Complex Regional Pain Syndrome (CRPS) is a rare, but often disabling pain disease. Biomarkers are lacking, but several inflammatory substances have been associated with the pathophysiology. This review outlines the current knowledge with respect to target biomolecules and the analytical tools available to measure them. Areas covered: Targets include cytokines, neuropeptides and resolvins; analysis strategies are thus needed for different classes of substances such as proteins, peptides, lipids and small molecules. Traditional methods like immunoassays are of importance next to state-of-the art high-resolution mass spectrometry techniques and 'omics' approaches. Expert commentary: Future biomarker studies need larger cohorts, which improve subgrouping of patients due to their presumed pathophysiology, and highly standardized workflows from sampling to analysis.


Assuntos
Síndromes da Dor Regional Complexa/metabolismo , Metaboloma , Técnicas de Diagnóstico Molecular/métodos , Proteoma/química , Biomarcadores/metabolismo , Síndromes da Dor Regional Complexa/genética , Síndromes da Dor Regional Complexa/patologia , Citocinas/genética , Citocinas/metabolismo , Humanos , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Proteoma/genética , Proteoma/metabolismo
3.
Pain Med ; 18(4): 764-772, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-27605590

RESUMO

Background: Many patients with complex regional pain syndrome (CRPS) report some foreignness of the affected limb, which is referred to as "neglect-like symptoms" (NLS). Despite similarities of the NLS reports to symptoms of body image disturbances in mental disorders, no study has been conducted to examine such associations. Methods: We investigated 50 patients with CRPS and 45 pain control patients (N = 27, chronic limb pain; N = 18, migraine headache). NLS, anxiety, depression, depersonalization, and somatization were assessed using validated questionnaires. Results: Seventy-two percent of the CRPS patients reported at least one NLS vs 29.6% and 33.3% in the two patient control groups. In limb pain controls, NLS correlated with pain intensity. In CRPS patients, NLS correlated with anxiety (rho = 0.658, P < 0.001), somatization (rho = 0.616, P < 0.001), depersonalization (rho = 0.634, P < 0.001), and pain catastrophizing (rho = 0.456, P < 0.01), but not with intensity of pain, duration of pain, or pain disability. Conclusions: In CRPS patients, NLS could be a result of somatization, depression, anxiety, and depersonalization, but probably not of pain. Whether these associations are causative must be clarified in longitudinal psychological studies.


Assuntos
Ansiedade/epidemiologia , Transtornos Dismórficos Corporais/epidemiologia , Síndromes da Dor Regional Complexa/epidemiologia , Despersonalização/epidemiologia , Depressão/epidemiologia , Transtornos da Percepção/epidemiologia , Transtornos Somatoformes/epidemiologia , Ansiedade/diagnóstico , Ansiedade/psicologia , Transtornos Dismórficos Corporais/diagnóstico , Transtornos Dismórficos Corporais/psicologia , Catastrofização , Causalidade , Comorbidade , Síndromes da Dor Regional Complexa/diagnóstico , Síndromes da Dor Regional Complexa/psicologia , Despersonalização/diagnóstico , Despersonalização/psicologia , Depressão/diagnóstico , Depressão/psicologia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transtornos da Percepção/diagnóstico por imagem , Transtornos da Percepção/psicologia , Fatores de Risco , Transtornos Somatoformes/diagnóstico , Transtornos Somatoformes/psicologia
4.
Fortschr Neurol Psychiatr ; 85(11): 683-689, 2017 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-29166692

RESUMO

The aim of this study was to compare the satisfaction and success of treatment for pain patients who were interdisciplinary (anaesthesiological, psychosomatic, neurological, orthopedic) treated or underwent neurological care alone. Methods We selected 183 patients who were treated in our neurological clinic and in our interdisciplinary pain management center (IST). Of these, 142 patients having polyneuropathy, headache or muskuloskelettal pain were included in the final analysis. 39 patients (27.5 %) were treated in the IST and 103 patients were treated exclusively by a neurologist. These patients were asked to complete a questionnaire, and were queried about the satisfaction and pain parameters. Results The neurological and multidisciplinary pain treatment led to a similar improvement in pain (p < 0.001). This effect was independent of the underlying disease. The interdisciplinary outpatient treatment resulted not primarily in an increased patient satisfaction. Conclusions The reduction of pain and patient satisfaction of neurological outpatient pain treatment were comparable with those of a multidisciplinary outpatient therapy. The only significant advantage of the interdisciplinary treatment was lower hospitalization rate after therapy. This result cannot evaluate the efficiency of inpatient or day hospital pain management, but suggests that in many cases a neurological outpatient pain therapy is sufficient, so that neurological outpatient care should be promoted.


Assuntos
Assistência Ambulatorial/organização & administração , Neurologia , Manejo da Dor , Equipe de Assistência ao Paciente/organização & administração , Satisfação do Paciente , Resultado do Tratamento , Adulto , Idoso , Anestesiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ortopedia , Medição da Dor , Medicina Psicossomática , Estudos Retrospectivos , Inquéritos e Questionários
5.
Exp Dermatol ; 22(4): 299-301, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23528219

RESUMO

The neuropeptides CGRP (calcitonin gene-elated peptide) and substance P (SP) mediate neurogenic inflammation. Both are degraded by the neutral endopeptidase (NEP) which can be blocked by phosphoramidon. The aim was to evaluate the effect of NEP inhibition on sweating and vasodilatation. Dermal microdialysis was performed on the skin of 39 subjects. Two fibres were perfused with phosphoramidon (0.01%, 0.02% or 0.2%), two with saline. Acetylcholine (ACh) was either added to the microdialysis perfusate (n = 30, 10(-2)  m) or thermoregulatory sweating was induced (n = 9). Co-application of phosphoramidon reduced cholinergic and thermoregulatory sweating. However, the flare size - a localized increase in superficial blood flow after ACh-application - was significantly increased. The increase in flare size is most probably due to increased CGRP levels. The inhibition of sweating by phosphoramidon may involve an increase in SP, a reduction in CGRP-degradation fragments or a direct inhibitory action of phosphoramidon.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Sudorese/fisiologia , Adulto , Axônios/fisiologia , Regulação da Temperatura Corporal/efeitos dos fármacos , Regulação da Temperatura Corporal/fisiologia , Feminino , Glicopeptídeos/farmacologia , Humanos , Masculino , Neprilisina/antagonistas & inibidores , Inibidores de Proteases/farmacologia , Reflexo/fisiologia , Pele/efeitos dos fármacos , Pele/inervação , Pele/metabolismo , Substância P/metabolismo , Sudorese/efeitos dos fármacos
6.
J Pharm Biomed Anal ; 205: 114307, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34392129

RESUMO

Complex Regional Pain Syndrome (CRPS) occurs in about 2% of patients after fracture of the limbs. In an earlier clinical study with 102 probands we have shown that the serum protease network in CRPS might be less effective. Based on these results we hypothesized that angiotensin-converting enzyme (ACE) and carboxypeptidase N (CPN) activity contribute to the differences of labeled bradykinin (DBK) degradation by patients' sera. Details of the enzymatic processes remained however unclear. The contributions of ACE and CPN in the serum degradation of DBK were studied using specific inhibitors. CPN1-ELISA was performed in serum. It was confirmed that the majority of DBK was degraded by ACE and CPN. The data delivered proof that the ACE serum activity was lowered in CRPS. High-resolution mass spectrometry was additionally used for protein expression analysis of sera of above study cohort (CRPS vs. healthy probands). According to principal component analysis of these data, significant differences between CRPS and control samples only occurred in sera of females younger than 46 years. In these CRPS patients, a number of defence / immunity-related proteins and members of the renin-angiotensin system (RAS) protein network were regulated. The impact of CPN in CRPS pathophysiology is subject to further investigation. The data support the hypothesis that both the RAS and the innate immune system might be affected in CRPS. A database of regulated serum proteins was established for future research.


Assuntos
Síndromes da Dor Regional Complexa , Peptídeo Hidrolases , Angiotensinas , Bradicinina , Carboxipeptidases , Feminino , Humanos
7.
Auton Neurosci ; 234: 102814, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33964567

RESUMO

Diabetic neuropathy (dNP) patients often suffer from severe neuropathic pain. It was suggested that alpha-1 adrenoceptor (α1-AR) hyperresponsiveness contributes to pain in dNP. The aim of our study was to quantify α1-AR expression using immunohistochemistry in skin biopsies of nine patients with painful diabetic neuropathy compared to 10 healthy controls. Additionally, the association between α1-AR expression and activation with spontaneous and sympathetically maintained pain (SMP) induced by intradermal injection of the α1-agonist phenylephrine was investigated. For control purposes the α2-agonist clonidine was injected in a different session. We found that dermal nerve density was significantly lower in dNP than in controls. However, α1-AR expression was significantly greater on cutaneous blood vessels and keratinocytes of dNP patients than controls. A similar trend, which failed to reach significance, was observed for dermal nerves. Intradermal injection of phenylephrine induced only minor pain, which resolved after a few minutes. Adrenergically evoked pain persisted for more than 15 min in only one patient, but none of the patients fulfilled the criteria for SMP (pain increase after injection of phenylephrine and decrease after clonidine). In conclusion, our results imply that SMP does not occur in dNP. However, elevated expression of α1-AR on keratinocytes and dermal blood vessels is an important finding, since this could contribute to dNP progression and supports the theory of receptor up-regulation of denervated structures. The implications of this α1-upregulation should be examined in further studies.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Dor , Fenilefrina/farmacologia , Receptores Adrenérgicos alfa 1 , Pele
8.
J Pain ; 22(10): 1294-1302, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33892152

RESUMO

Matrix metalloproteinases (MMP)-2 and MMP-9 play important roles in inflammation as well as in pain processes. For this reason, we compared the concentrations of these enzymes in skin and serum of patients with complex regional pain syndrome (CRPS), other pain diseases and healthy subjects. We analyzed ipsi- and contralateral skin biopsies of 18 CRPS patients, as well as in 10 pain controls and 9 healthy subjects. Serum samples were analyzed from 20 CRPS, 17 pain controls and 17 healthy subjects. All samples were analyzed with ELISA. Concentrations were then compared to clinical data as well as to quantitative sensory testing data.MMP-2 was increased in both ipsi- and contralateral skin biopsies of CRPS patients compared to healthy subjects. While low ipsilateral MMP-2 was associated with trophic changes, contralateral MMP-2 inversely correlated with the CRPS severity. MMP-9 was also locally increased in ipsilateral CRPS skin, and higher ipsi- and contralateral MMP-9 levels correlated with CRPS severity. We conclude that MMP-2 and MMP-9 are differently expressed depending on the clinical phenotype in CRPS. PERSPECTIVE: This article describes an upregulation of MMPs in CRPS and pain controls and shows different expression of MMP-2 and -9 depending on clinical phenotype in CRPS. These results provide evidence that MMP-2 and -9 play a key role in CRPS pathophysiology.


Assuntos
Síndromes da Dor Regional Complexa/metabolismo , Síndromes da Dor Regional Complexa/fisiopatologia , Inflamação/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Adulto , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Pele
9.
Neurol Res Pract ; 2: 16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324922

RESUMO

2019 the DGN (Deutsche Gesellschaft für Neurology) published a new guideline on the diagnosis and non-interventional therapy of neuropathic pain of any etiology excluding trigeminal neuralgia and CRPS (complex regional pain syndrome). Neuropathic pain occurs after lesion or damage of the somatosensory system. Besides clinical examination several diagnostic procedures are recommended to assess the function of nociceptive A-delta and C-Fibers (skin biopsy, quantitative sensory testing, Laser-evoked potentials, Pain-evoked potentials, corneal confocal microscopy, axon reflex testing). First line treatment in neuropathic pain is pregabalin, gabapentin, duloxetine and amitriptyline. Second choice drugs are topical capsaicin and lidocaine, which can also be considered as primary treatment in focal neuropathic pain. Opioids are considered as third choice treatment. Botulinum toxin can be considered as a third choice drug for focal limited pain in specialized centers only. Carbamazepine and oxcarbazepine cannot be generally  recommended, but might be helpful in single cases. In Germany, cannabinoids can be prescribed, but only after approval of reimbursement. However, the use is not recommended, and can only be considered as off-label therapy within a multimodal therapy concept.

11.
Pain ; 160(6): 1402-1409, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30694931

RESUMO

Complex regional pain syndrome (CRPS) develops after fracture. The acute CRPS phenotype resembles exaggerated inflammation, which is explained by local and systemic activation of a proinflammatory network including peptides and cytokines. Epidemiologic data suggest that inactivation of the peptidase angiotensin-converting enzyme in patients treated for hypertension increases the odds to develop CRPS. This hint leads us to investigate the serum protease network activity in patients with CRPS vs respective controls. For this purpose, we developed a dabsyl-bradykinin (DBK)-based assay and used it to investigate patients with CRPS, as well as healthy and pain (painful diabetic neuropathy [dPNP]) controls. The major result is that the degradation of DBK to fragments 1-8 and 1-5 in healthy control and dPNP is shifted to higher values for DBK1-8 and lower values for DBK1-5 at 1 hour of incubation in patients with CRPS. Using this novel reporter peptide assay, we have been able to show that the resolving protease network for mediators such as BK might be different in patients with CRPS; having a look at the clinical signs, which resemble inflammation, this resolving protease network is probably less effective in CRPS.


Assuntos
Bradicinina/farmacologia , Síndromes da Dor Regional Complexa/fisiopatologia , Citocinas/sangue , Peptídeo Hidrolases/sangue , Adulto , Síndromes da Dor Regional Complexa/sangue , Neuropatias Diabéticas/sangue , Feminino , Humanos , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Medição da Dor , Peptidil Dipeptidase A/sangue , Distrofia Simpática Reflexa/sangue , Distrofia Simpática Reflexa/diagnóstico
12.
Pain ; 159(5): 978-986, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29419655

RESUMO

Neglect-like symptoms (NLS) are frequently observed in complex regional pain syndrome (CRPS). The clinical meaning of NLS, however, is largely unknown. Therefore, this study sets out to assess the importance of NLS for patient outcome and to explore their clinical correlates. We assessed NLS in a group of 53 patients with CRPS and compared the results to 28 healthy volunteers. To define the origin of the NLS reports, we tested the subjective visual midline, performed a limb-laterality recognition test, and quantitative sensory testing. In addition, psychological and pain assessment scales were completed. Tests were analyzed with univariate and multivariate approaches. After 6 months, patients were reassessed and the influence of NLS on pain outcome was determined. Most patients reported NLS in the questionnaire, whereas subjective visual midline and limb-laterality recognition test in contrast to previous studies did not reveal perceptual disturbances. Neglect-like symptom scores were associated with pain and pain catastrophizing in acute CRPS and anxiety and thermal sensory loss in chronic CRPS. Furthermore, high NLS scores had a negative impact on pain outcome after 6 months. Our results indicate that NLS have a different meaning in acute and chronic CRPS and might be of prognostic value. Possibly, treatment should focus on reducing NLS.


Assuntos
Atenção/fisiologia , Catastrofização/complicações , Síndromes da Dor Regional Complexa/complicações , Dor/complicações , Transtornos da Percepção/complicações , Percepção Visual/fisiologia , Adulto , Idoso , Catastrofização/psicologia , Síndromes da Dor Regional Complexa/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/psicologia , Medição da Dor , Transtornos da Percepção/psicologia , Inquéritos e Questionários
13.
J Pain ; 19(10): 1102.e1-1102.e19, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29684510

RESUMO

Distal limb fracture is the most common cause of complex regional pain syndrome (CRPS), thus the rodent tibia fracture model (TFM) was developed to study CRPS pathogenesis. This comprehensive review summarizes the published TFM research and compares these experimental results with the CRPS literature. The TFM generated spontaneous and evoked pain behaviors, inflammatory symptoms (edema, warmth), and trophic changes (skin thickening, osteoporosis) resembling symptoms in early CRPS. Neuropeptides, inflammatory cytokines, and nerve growth factor (NGF) have been linked to pain behaviors, inflammation, and trophic changes in the TFM model and proliferating keratinocytes were identified as the primary source of cutaneous cytokines and NGF. Tibia fracture also activated spinal glia and upregulated spinal neuropeptide, cytokine, and NGF expression, and in the brain it changed dendritic architecture. B cell-expressed immunoglobulin M antibodies also contributed to pain behavior, indicating a role for adaptive immunity. These results modeled many findings in early CRPS, but significant differences were also noted. PERSPECTIVE: Multiple neuroimmune signaling mechanisms contribute to the pain, inflammation, and trophic changes observed in the injured limb of the rodent TFM. This model replicates many of the symptoms, signs, and pathophysiology of early CRPS, but most post-fracture changes resolve within 5 months and may not contribute to perpetuating chronic CRPS.


Assuntos
Síndromes da Dor Regional Complexa , Modelos Animais de Doenças , Fraturas da Tíbia , Animais , Camundongos , Ratos
15.
Life Sci ; 80(24-25): 2239-42, 2007 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-17276464

RESUMO

Non-neuronal acetylcholine (ACh) is expressed in epithelial, endothelial and immune cells. For example, the in vivo release of ACh from the human skin pretreated with botulinum toxin has recently been demonstrated. In the present experiments the effects of light (sunlight and solar radiation by a commercial UV-A applier) and of a tactile stimulus on the release of non-neuronal ACh were investigated. Release of ACh from the proximal and distal shin, i.e. anterior tibial region, was measured by dermal microdialysis in 20 min samples over a time period of at least 140 min. Control experiments were performed in a dark room throughout. In some experiments volunteers were exposed to sunshine (80-140 min) or the shin region was illuminated (80-95 min) by a commercial UV-A lamp (400 W at a distance of 50 cm). In control experiments ACh release between 20 and 80 min (B1) amounted to 118+/-32 pmol (n=17) and gradually declined between 80 and 140 min (B2) to 112+/-34 pmol, resulting in a B2/B1 ratio of 0.95. When the skin was exposed to sunlight ACh release increased from 205+/-58 pmol (B1) to 349+/-122 pmol resulting in a B2/B1 ratio of 1.70. UV-A radiation, however, had no significant effect on the B2/B1 ratio. When very smooth tactile stimuli were applied by a cotton wool tip for 20 min to the skin close to the microdialysis membranes in a dark room, ACh release was increased from 9+/-2 pmol/20 min to 52+/-36 (n=7). In conclusion, the in vivo release of ACh from the human skin appears to be regulated by external stimuli like sunlight and tactile stimuli.


Assuntos
Acetilcolina/metabolismo , Pele/metabolismo , Adulto , Feminino , Humanos , Injeções Intradérmicas , Masculino , Microdiálise/métodos , Neurônios/metabolismo , Estimulação Física , Pele/efeitos da radiação , Luz Solar , Fatores de Tempo , Raios Ultravioleta
16.
J Pain ; 18(4): 468-476, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28062308

RESUMO

Bone fracture with subsequent immobilization of the injured limb can cause complex regional pain syndrome (CRPS) in humans. Mechanisms of CRPS are still not completely understood but bone fracture with casting in mice leads to a similar post-traumatic inflammation as seen in humans and might therefore be an analog to human CRPS. In this article we report behavioral and spinal electrophysiological changes in mice that developed swelling of the paw, warming of the skin, and pain in the injured limb after bone fracture. The receptive field sizes of spinal neurons representing areas of the hind paws increased after trauma and recovered over time-as did the behavioral signs of inflammation and pain. Interestingly, both sides-the ipsi- and the contralateral limb-showed changes in mechanical sensitivity and neuronal network organization after the trauma. The characteristics of evoked neuronal responses recorded in the dorsal horn of the mice were similar between uninjured controls and fractured animals. However, we saw a caudal extension of the represented area of the hind paw in the spinal cord at the injured side and an occurrence of large receptive fields of wide dynamic range neurons. The findings in mice compare with human symptoms in CRPS with ipsi- and also contralateral allodynia and pain. In all mice tested, all signs subsided 12 weeks after trauma. Our data suggest a significant reorganization of spinal circuitry after limb trauma, in a degree more comprehensive than most models of neuropathies. This process seems to be reversible in the rodent. PERSPECTIVE: The discovery of enlarged spinal neuronal receptive fields and caudal extension of the representation area of the injured body part, which subsides several weeks after a bone trauma in mice, might give hope to patients of CRPS if-in the future-we are able to translate the rodent recovery mechanisms to post-traumatic humans.


Assuntos
Síndromes da Dor Regional Complexa/etiologia , Síndromes da Dor Regional Complexa/patologia , Fraturas Ósseas/complicações , Rede Nervosa/fisiopatologia , Neurônios/fisiologia , Medula Espinal/patologia , Potenciais de Ação/fisiologia , Animais , Modelos Animais de Doenças , Edema/etiologia , Estimulação Elétrica , Hiperalgesia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Medição da Dor , Limiar da Dor/fisiologia , Estimulação Física , Temperatura Cutânea/fisiologia , Estatísticas não Paramétricas , Fatores de Tempo , Suporte de Carga/fisiologia
17.
Pain ; 158(8): 1430-1436, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28715350

RESUMO

Clinical diagnosis of complex regional pain syndrome (CRPS) is a dichotomous (yes/no) categorization, a format necessary for clinical decision making. Such dichotomous diagnostic categories do not convey an individual's subtle gradations in the severity of the condition over time and have poor statistical power when used as an outcome measure in research. This prospective, international, multicenter study slightly modified and further evaluated the validity of the CRPS Severity Score (CSS), a continuous index of CRPS severity. Using a prospective design, medical evaluations were conducted in 156 patients with CRPS to compare changes over time in CSS scores between patients initiating a new treatment program and patients on stable treatment regimens. New vs stable categorizations were supported by greater changes in pain and function in the former. Results indicated that CSS values in the stable CRPS treatment group exhibited much less change over time relative to the new treatment group, with intraclass correlations nearly twice as large in the former. A calculated smallest real difference value revealed that a change in the CSS of ≥4.9 scale points would indicate real differences in CRPS symptomatology (with 95% confidence). Across groups, larger changes in CRPS features on the CSS over time were associated in the expected direction with greater changes in pain intensity, fatigue, social functioning, ability to engage in physical roles, and general well-being. The overall pattern of findings further supports the validity of the CSS as a measure of CRPS severity and suggests it may prove useful in clinical monitoring and outcomes research.


Assuntos
Síndromes da Dor Regional Complexa/diagnóstico , Síndromes da Dor Regional Complexa/fisiopatologia , Dor/fisiopatologia , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Estudos Prospectivos , Índice de Gravidade de Doença
18.
Br J Pharmacol ; 147(2): 183-7, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16273117

RESUMO

1.--Acetylcholine is synthesized in the majority of non-neuronal cells, for example in human skin. In the present experiments, the in vivo release of acetylcholine was measured by dermal microdialysis. 2.--Two microdialysis membranes were inserted intradermally at the medial shank of volunteers. Physiological saline containing 1 muM neostigmine was perfused at a constant rate of 4 microl min(-1) and the effluent was collected in six subsequent 20 min periods. Acetylcholine was measured by high-pressure liquid chromatography (HPLC) combined with bioreactors and electrochemical detection. 3.--Analysis of the effluent by HPLC showed an acetylcholine peak that disappeared, when the analytical column was packed with acetylcholine-specific esterase, confirming the presence of acetylcholine. 4.--In the absence of neostigmine, 71+/-51 pmol acetylcholine (n=4) was found during a 120 min period. The amount increased to 183+/-43 pmol (n=34), when the perfusion medium contained 1 microM neostigmine. 5.--Injection of 100 MU botulinum toxin subcutaneously blocked sweating completely, but the release of acetylcholine was not affected (botulinum toxin treated skin: 116+/-70 pmol acetylcholine/120 min; untreated skin: 50+/-20 pmol; n=4). 6.--Quinine (1 mM), inhibitor of organic cation transporters, and carnitine (0.1 mM), substrate of the Na(+)-dependent carnitine transporter OCTN2, tended to reduce acetylcholine release (by 40%, not significant). 7.--Our experiments demonstrate, for the first time, the in vivo release of non-neuronal acetylcholine in human skin. Organic cation transporters are not predominantly involved in the release of non-neuronal acetylcholine from the human skin.


Assuntos
Acetilcolina/metabolismo , Toxinas Botulínicas/farmacologia , Pele/efeitos dos fármacos , Adulto , Toxinas Botulínicas/administração & dosagem , Carnitina/farmacologia , Feminino , Humanos , Injeções Subcutâneas , Masculino , Microdiálise , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Quinina/farmacologia , Pele/metabolismo , Membro 5 da Família 22 de Carreadores de Soluto , Glândulas Sudoríparas/efeitos dos fármacos , Glândulas Sudoríparas/metabolismo
19.
Neuropeptides ; 59: 57-62, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27344069

RESUMO

Calcitonin gene related peptide (CGRP) and substance P (SP) are neuropeptides that are simultaneously released from nociceptive C-fibers. CGRP is a potent vasodilator, inducing a long-lasting increase in superficial skin blood flow, whereas SP induces only a brief vasodilation but a significant plasma extravasation. CGRP and SP may play important roles in the pathophysiology of various pain states but little is known about their interaction. Different concentrations of SP (ranging from 10-5M to 10-9M) were applied to the volar forearm of 24 healthy subjects via dermal microdialysis. SP was applied either alone or in combination with CGRP10-9M and CGRP 10-6M. As expected, SP induced a transient increase in skin blood flow that decayed shortly after application. This transient blood flow peak was blunted with co-application of CGRP 10-9M and inhibited with co-application of CGRP10-6M. SP alone induced plasma protein extravasation (PPE). However, when CGRP10-6M was added, the PPE significantly increased. Our results demonstrate a complex interaction of the neuropeptides CGRP and SP. CGRP10-6M prevented SP-induced early vasodilation but augmented SP-induced PPE. These interactions might explain why vascular symptoms in chronic pain can differ strikingly between individuals.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Pele/efeitos dos fármacos , Substância P/farmacologia , Vasodilatação/efeitos dos fármacos , Relação Dose-Resposta a Droga , Antebraço/irrigação sanguínea , Humanos , Pele/irrigação sanguínea , Pele/metabolismo , Adulto Jovem
20.
Pain ; 157(8): 1674-81, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27023422

RESUMO

Limited research suggests that there may be Warm complex regional pain syndrome (CRPS) and Cold CRPS subtypes, with inflammatory mechanisms contributing most strongly to the former. This study for the first time used an unbiased statistical pattern recognition technique to evaluate whether distinct Warm vs Cold CRPS subtypes can be discerned in the clinical population. An international, multisite study was conducted using standardized procedures to evaluate signs and symptoms in 152 patients with clinical CRPS at baseline, with 3-month follow-up evaluations in 112 of these patients. Two-step cluster analysis using automated cluster selection identified a 2-cluster solution as optimal. Results revealed a Warm CRPS patient cluster characterized by a warm, red, edematous, and sweaty extremity and a Cold CRPS patient cluster characterized by a cold, blue, and less edematous extremity. Median pain duration was significantly (P < 0.001) shorter in the Warm CRPS (4.7 months) than in the Cold CRPS subtype (20 months), with pain intensity comparable. A derived total inflammatory score was significantly (P < 0.001) elevated in the Warm CRPS group (compared with Cold CRPS) at baseline but diminished significantly (P < 0.001) over the follow-up period, whereas this score did not diminish in the Cold CRPS group (time × subtype interaction: P < 0.001). Results support the existence of a Warm CRPS subtype common in patients with acute (<6 months) CRPS and a relatively distinct Cold CRPS subtype most common in chronic CRPS. The pattern of clinical features suggests that inflammatory mechanisms contribute most prominently to the Warm CRPS subtype but that these mechanisms diminish substantially during the first year postinjury.


Assuntos
Síndromes da Dor Regional Complexa/diagnóstico , Inflamação/fisiopatologia , Adulto , Síndromes da Dor Regional Complexa/fisiopatologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Fenótipo , Estudos Prospectivos
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa