Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes.

Neuropathic pain is accompanied by both positive and negative sensory signs. To explore the spectrum of sensory abnormalities, 1236 patients with a clinical diagnosis of neuropathic pain were assessed by quantitative sensory testing (QST) following the protocol of DFNS (German Research Network on Neuropathic Pain), using both thermal and mechanical nociceptive as well as non-nociceptive stimuli. Data distributions showed a systematic shift to hyperalgesia for nociceptive, and to hypoesthesia for non-nociceptive parameters. Across all parameters, 92% of the patients presented at least one abnormality. Thermosensory or mechanical hypoesthesia (up to 41%) was more frequent than hypoalgesia (up to 18% for mechanical stimuli). Mechanical hyperalgesias occurred more often (blunt pressure: 36%, pinprick: 29%) than thermal hyperalgesias (cold: 19%, heat: 24%), dynamic mechanical allodynia (20%), paradoxical heat sensations (18%) or enhanced wind-up (13%). Hyperesthesia was less than 5%. Every single sensory abnormality occurred in each neurological syndrome, but with different frequencies: thermal and mechanical hyperalgesias were most frequent in complex regional pain syndrome and peripheral nerve injury, allodynia in postherpetic neuralgia. In postherpetic neuralgia and in central pain, subgroups showed either mechanical hyperalgesia or mechanical hypoalgesia. The most frequent combinations of gain and loss were mixed thermal/mechanical loss without hyperalgesia (central pain and polyneuropathy), mixed loss with mechanical hyperalgesia in peripheral neuropathies, mechanical hyperalgesia without any loss in trigeminal neuralgia. Thus, somatosensory profiles with different combinations of loss and gain are shared across the major neuropathic pain syndromes. The characterization of underlying mechanisms will be needed to make a mechanism-based classification feasible.

Reference values for quantitative sensory testing in children and adolescents: developmental and gender differences of somatosensory perception.

The Quantitative Sensory Testing (QST) protocol of the German research network on neuropathic pain (DFNS) encompassing all somatosensory modalities assesses the functioning of different nerve fibers and of central pathways. The aim of our study was: (1) to explore, whether this QST protocol is feasible for children, (2) to detect distribution properties of QST data and the impact of body site, age and gender and (3) to establish reference values for QST in children and adolescents. The QST protocol of the DFNS with modification of instructions and pain rating was used in 176 children aged 6.12-16.12years for six body sites. QST was feasible for children over 5years of age. ANOVAs revealed developmental, gender and body site differences of somatosensory functions similar to adults. The face was more sensitive than the hand and/or foot. Younger children (6-8years) were generally less sensitive to all thermal and mechanical detection stimuli but more sensitive to all pain stimuli than older (9-12years) children, whereas there were little differences between older children and adolescents (13-17years). Girls were more sensitive to thermal detection and pain stimuli, but not to mechanical detection and pain stimuli. Reference values differ from adults, but distribution properties (range, variance, and side differences) were similar and plausible for statistical factors. Our results demonstrate that the full QST protocol is feasible and valid for children over 5years of age with their own reference values.

Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups.

OBJECTIVES: The Complex Regional Pain Syndrome I (CRPS I) is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. METHODS: To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP), White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-a) and its soluble Receptors I/II, soluble Selectins (E,L,P), Substance-P (SP), and Calcitonin Gene-Related Peptide (CGRP) at different time points in venous blood from patients with acute (AC) and chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE), and from healthy volunteers (C). RESULTS: No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra- or interindividual correlation of parameters with clinical course (e.g. chronification) or outcome was detectable. CONCLUSION: Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this pilot study. Determination of systemic inflammatory parameters is not yet helpful in diagnostic and follow-up of CRPS I.

[Procedure for certification of QST laboratories]. / Zertifizierungsrichtlinien für QST-Labore.

Quantitative sensory testing (QST) is the standardized assessment of the somatosensory system comprising all sensory submodalities. In the German Research Network on Neuropathic Pain (DFNS), a QST-battery consisting of 13 parameters has been established and nationwide normative data have been collected. In contrast to conventional electrophysiology, QST allows detecting negative and positive sensory signs of both large and small fiber systems. However, as a subjective psychophysical method it is critically dependent on patients'/healthy subjects' cooperation thus strictly standardized protocols and instructions are needed to allow across laboratory comparisons. To facilitate more widespread use of QST, the German Pain Society (DGSS) and the DFNS have initiated a certification procedure for QST quality standards. Therefore, structural, procedural criteria and outcome parameters were establishd and are hereby presented. By maintaining high quality standards, the certification of QST is intended to contribute to a better understanding of the mechanisms behind neuropathic pain syndromes and thereby improve patient care as well as sensory assessment in clinical studies on the treatment of neuropathic pain syndromes.

[Pain in the left hand especially pronounced in the ring finger and small finger]. / Schmerzen der linken Hand mit Betonung am Ring- und Kleinfinger.

A case is described of a female patient, who presented with permanent stabbing and burning pain in the ring finger and small finger of the left hand. Because of this pain neurolysis of the sulcus ulnaris had been carried out 4 months previously, which did not result in an improvement but led to a spreading of the symptoms to the whole hand. Diagnostic three-phase skeletal scintigraphy and neurography were performed. In 1999 breast cancer was diagnosed and surgically treated. Oncological follow-up 2 months before presentation revealed no conspicuous findings.Readers are encouraged to make their own diagnosis on the basis of the clinical findings and to discuss the case online (http://blogs.springer.com/DerSchmerz).

Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values.

The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.