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