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Prognostic value of measures of central hypersensitivity in patients with low back pain

English title Prognostic value of measures of central hypersensitivity in patients with low back pain
Applicant Curatolo Michele
Number 122358
Funding scheme Project funding (special)
Research institution Universitätsklinik für Anästhesiologie und Schmerztherapie Inselspital
Institution of higher education University of Berne - BE
Main discipline Clinical Pathophysiology
Start/End 01.10.2008 - 30.09.2011
Approved amount 312'624.00
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All Disciplines (2)

Discipline
Clinical Pathophysiology
Diseases of Bones and Joints

Keywords (7)

Central hypersensitivity; Central sensitization; Chronic pain; Low back pain; Musculoskeletal pain; prognosis; diagnosis

Lay Summary (German)

Lead
Lay summary
rundlageChronische Rückenschmerzen sind mit einer erhöhten Empfindlichkeit des zentralen Nervensystems verbunden. Die überempfindlichen Neuronen verstärken die Wahrnehmung der peripheren Reize, was zu einer erhöhten Schmerzempfindung führt. Es besteht der Verdacht, dass diese Überempfindlichkeit bei akuten Rückenschmerzen auftritt und ein Risikofaktor für die Entwicklung chronischer Schmerzen darstellt.ZieleDie zwei Ziele dieses Projekts sind es: 1) Methoden zu etablieren, um die Überempfindlichkeit des zentralen Nervensystems bei Patienten mit chronischen Rückenschmerzen zu identifizieren und zu quantifizieren; 2) Zu prüfen, ob eine Überempfindlichkeit des zentralen Nervensystems bereits bei akuten Rückenschmerzen auftritt und die Prognose in bezug auf die Entwicklung der chronischen Schmerzen ungünstig beeinflusst.MethodenDie Empfindlichkeit des zentralen Nervensystems wird mittels künstlich provozierter schmerzhafter Reize getestet. Zusätzlich werden psychologische Parameter und verschiedene Aspekte der Schmerzempfindung (z.B. die Lebensqualität) erfasst. In einem ersten Teil werden diese Parameter bei Patienten mit chronischen Rückenschmerzen erfasst. Die Resultate werden mit Daten bei 300 gesunden Probanden verglichen, die bereits von unserer Gruppe erhoben wurden. Dadurch werden wir Kriterien für die Diagnose der zentralen Überempfindlichkeit bei individuellen Patienten definieren. In einem zweiten Teil werden wir die gleichen Messungen bei Patienten mit akuten Rückenschmerzen (d.h. Schmerzen seit maximal 4 Wochen) erfassen. Sechs Monate später wird evaluiert, ob diese Patienten chronische Rückenschmerzen entwickelt haben oder nicht. Der Zusammenhang zwischen Empfindlichkeit des zentralen Nervensystems in der Akutphase und Entwicklung chronischer Schmerzen wird statistisch evaluiert.Erwartete VorteileDie Studie wird Methoden etablieren, die zur Diagnose und Quantifizierung der zentralen Überempfindlichkeit bei individuellen Patienten in der Klinik angewandt werden können. Die Identifizierung der zentralen Überempfindlichkeit kann die invalidisierenden Schmerzen erklären, auch wenn kleine oder gar keine Verletzungen durch die konventionellen Mittel (z.B. klinische Untersuchung oder Röntgen) diagnostisiert werden können. Eine Selektion der Patienten in der Akutphase, die zur Entwicklung der chronischen Schmerzen neigen, ist äusserst wichtig. So könnten präventive und therapeutische Massnahmen auf die Risikopatienten konzentriert werden. Ferner könnte man Patienten für die Evaluation neuer Therapien gegen die Überempfindlichkeit des zentralen Nervensystems in Rahmen von Forschungsprojekte gezielt auswählen.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Factor analysis of responses to thermal, electrical, and mechanical painful stimuli supports the importance of multi-modal pain assessment.
Neziri Alban Y, Curatolo Michele, Nüesch Eveline, Scaramozzino Pasquale, Andersen Ole K, Arendt-Nielsen Lars, Jüni Peter (2011), Factor analysis of responses to thermal, electrical, and mechanical painful stimuli supports the importance of multi-modal pain assessment., in Pain, 152(5), 1146-55.
Reference values of mechanical and thermal pain tests in a pain-free population.
Neziri Alban Y, Scaramozzino Pasquale, Andersen Ole K, Dickenson Anthony H, Arendt-Nielsen Lars, Curatolo Michele (2011), Reference values of mechanical and thermal pain tests in a pain-free population., in European journal of pain (London, England), 15(4), 376-83.
Test-retest reliability of the nociceptive withdrawal reflex and electrical pain thresholds after single and repeated stimulation in patients with chronic low back pain.
Biurrun Manresa José A, Neziri Alban Y, Curatolo Michele, Arendt-Nielsen Lars, Andersen Ole K (2011), Test-retest reliability of the nociceptive withdrawal reflex and electrical pain thresholds after single and repeated stimulation in patients with chronic low back pain., in European journal of applied physiology, 111(1), 83-92.
Generalized expansion of nociceptive reflex receptive fields in chronic pain patients.
Neziri Alban Y, Haesler S, Petersen-Felix Steen, Müller Michael, Arendt-Nielsen Lars, Manresa Jose Biurrun, Andersen Ole K, Curatolo Michele (2010), Generalized expansion of nociceptive reflex receptive fields in chronic pain patients., in Pain, 151(3), 798-805.
The nociceptive withdrawal reflex: normative values of thresholds and reflex receptive fields.
Neziri Alban Y, Andersen Ole K, Petersen-Felix Steen, Radanov Bogdan, Dickenson Anthony H, Scaramozzino Pasquale, Arendt-Nielsen Lars, Curatolo Michele (2010), The nociceptive withdrawal reflex: normative values of thresholds and reflex receptive fields., in European journal of pain (London, England), 14(2), 134-41.
New method for quantification and statistical analysis of nociceptive reflex receptive fields in humans.
Neziri Alban Y, Curatolo Michele, Bergadano Alessandra, Petersen-Felix Steen, Dickenson Anthony, Arendt-Nielsen Lars, Andersen Ole K (2009), New method for quantification and statistical analysis of nociceptive reflex receptive fields in humans., in Journal of neuroscience methods, 178(1), 24-30.
Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients
Neziri A.Y., Dickenmann M., Scaramozzino P., Andersen O.K., Arendt-Nielsen L., Dickenson A.H., Curatolo M., Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients, in Pain.

Awards

Title Year
Best poster at the Annual Congress of the Swiss Society for the Study of Pain 2010
Best scientific presentation, Annual Congress of the Swiss Society for the Study of Pain 2008
Best scientific presentation, Annual Congress of the Swiss Society of Anaesthesia and Reanimation 2008

Associated projects

Number Title Start Funding scheme
138361 Prognostic values of measures of altered pain processing for the outcome of surgery in patients with chronic low back pain 01.02.2012 Project funding

Abstract

BackgroundPatients with chronic low back pain may experience a hyper-excitability of the central nervous system (central hypersensitivity), which contributes to the experienced severity of pain. The prognostic value of measures of central hypersensitivity is unclear. ObjectivesTo determine the prognostic value of measures of central hypersensitivity in patients with low back pain.DesignCross-sectional case-control study followed by a prospective cohort study.SettingCase-control study: Tertiary care center at Bern University Hospital.Cohort study: Primary care setting of the mediX practice network, Bern.PatientsCase-control study: 300 pain-free control individuals were already recruited and examined. For the purpose of the study, 40 cases with chronic low-back pain will be recruited, with chronic low back pain defined as the presence of low pack pain on most days for the duration of three months or longer. Cohort study: 140 individuals with an acute episode of low back pain and no history of chronic low back pain. Variables of interestCase-control study: Primary prognostic variable will be the pain tolerance threshold at the second toe assessed using an electronic pressure algometer, with the threshold defined as the pressure in kPa at which a further increase in perceived pain is deemed intolerable by examined individuals. The following measures of central hypersensitivity will be exploratory secondary prognostic variables: 1. pain detection threshold on pressure and other measures of stimulus-specific pain hypersensitivity (pain detection and pain tolerance threshold to electrical stimulation, heat and cold stimulation); 2. tissue-specific pain hypersensitivity (thresholds to skin and muscle stimulation); 3. localized and widespread pain hypersensitivity (stimulation at the areas of pain and at distant areas); 4. spinal cord excitability (spinal nociceptive reflexes); 5. spinal cord reorganization (assessment of reflex receptive fields); and 6. temporal summation (induction of short-lasting central hyper-excitability by repeated stimulation). Primary and all secondary prognostic variables were already assessed in the 300 healthy controls.Cohort study: The pain tolerance threshold at the second toe will be the primary prognostic variable and the other measures of central hypersensitivity described above will be exploratory secondary prognostic variables. Descending modulation (diffuse noxious inhibitory control) and cortical reorganization (multichannel electro-encephalography) will be additional secondary prognostic variables for this study.Clinical primary outcomes will be the presence or absence of chronic low back pain in the case-control study, and the occurrence of chronic low back pain at follow-up in the cohort study.AnalysisCase-control study: We will determine means and standard deviations as measures of the distribution of primary and secondary prognostic variables in cases and controls. Then, we will estimate sensitivities, specificities and likelihood ratios from fitted receiver operating characteristic curves for different cut-offs used to distinguish between pathological and normal values of measures of central hypersensitivity. We will determine the relationship between different frequencies of chronic low back pain in different populations (e.g. primary versus tertiary care) and the estimated probability of developing chronic low back pain given a pathological or normal value of measures of central hypersensitivity. For this purpose, we will use a series of different cut-offs to distinguish between pathological and normal values. Among cases, we will use least square linear regression models to examine the association of measures of central hypersensitivity with pain intensity, disability and different assessments of psychological status.Cohort study: We will use least square logistic regression models to determine the association of mechanisms of central hypersensitivity with prognosis, i.e. the presence or absence of chronic low back pain after 6 months. The analysis will be crude and adjusted for risk factors associated with the occurrence of chronic low back pain. Then, we will estimate likelihood ratios for positive and negative tests from fitted receiver operating characteristic curves and will calculate probabilities of chronic low back pain given a positive or negative test using different cut-offs as described above.RelevanceChronic low back pain is a considerable burden for patients and the society. It causes suffering, disability, social problems and extremely high costs. Central hypersensitivity may have a clinically relevant influence on the occurrence and severity of chronic low back pain. An understanding of the prognostic value of measures of central hypersensitivity in patients with acute low back pain may inform our attempts of an early stratification of individuals according to their risk to develop chronic low back pain. The assessment of these measures may allow the characterization of subgroups of patients for clinical trials on novel pharmacological approaches towards the treatment of central hypersensitivity in individuals at risk for or those suffering from chronic low back pain.
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