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.

Objective. To use a combination of magnetic resonance diffusion-tensor imaging (MR-DTI) and MR imaging of voxel-based morphometry (MR-VBMFibromyalgia syndrome (FMS) belongs to a group of common functional somatic syndromes that are characterized by chronic widespread pain and are often accompanied by functional disturbance (dizziness, vertigo, palpitations, and peripheral edema) in different organ systems and symptoms of sleep disturbance, anxiety, memory problems, fatigue, and exhaustion. Because of the association between FMS development and severe organic illness, accidents, or stressful life events, FMS has also been regarded as a stress-related disorder (1). The combination of chronic widespread pain, sleep disturbance, and pronounced and ongoing stress symptoms is highly disabling, yet there is no universally effective treatment, and the pathophysiologic features of FMS are incompletely understood. Although this disorder has frequently been described as musculoskeletal or Supported by funds from the Departments of Anaesthesiology and Radiology, Klinikum Grosshadern, Ludwig-Maximilians University.

To evaluate immediate effects of two different modes of acupuncture on motion-related pain and cervical spine mobility in chronic neck pain patients compared to a sham procedure. Thirty-six patients with chronic neck pain and limited cervical spine mobility participated in a prospective, randomized, double-blind, sham-controlled crossover trial. Every patient was treated once with needle acupuncture at distant points, dry needling (DN) of local myofascial trigger points and sham laser acupuncture (Sham). Outcome measures were motion-related pain intensity (visual analogue scale, 0-100 mm) and range of motion (ROM). In addition, patients scored changes of general complaints using an 11-point verbal rating scale. Patients were assessed immediately before and after each treatment by an independent (blinded) investigator. Multivariate analysis was used to assess the effects of true acupuncture and needle site independently. For motion-related pain, use of acupuncture at non-local points reduced pain scores by about a third (11.2 mm; 95% CI 5.7, 16.7; P = 0.00006) compared to DN and sham. DN led to an estimated reduction in pain of 1.0 mm (95% CI -4.5, 6.5; P = 0.7). Use of DN slightly improved ROM by 1.7 degrees (95% CI 0.2, 3.2; P = 0.032) with use of non-local points improving ROM by an additional 1.9 degrees (95% CI 0.3, 3.4; P = 0.016). For patient assessment of change, non-local acupuncture was significantly superior both to Sham (1.7 points; 95% CI 1.0, 2.5; P = 0.0001) and DN (1.5 points; 95% CI 0.4, 2.6; P = 0.008) but there was no difference between DN and Sham (0.1 point; 95% CI -1.0, 1.2; P = 0.8). Acupuncture is superior to Sham in improving motion-related pain and ROM following a single session of treatment in chronic neck pain patients. Acupuncture at distant points improves ROM more than DN; DN was ineffective for motion-related pain.

BackgroundSensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS). In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST) in comparison to an age and gender matched control group.Methods61 patients presenting with CRPS I of the upper extremity and 56 healthy subjects were prospectively assessed using QST. The patients' warm and cold detection thresholds (WDT; CDT), the heat and cold pain thresholds (HPT; CPT) and the occurrence of paradoxical heat sensation (PHS) were observed.ResultsIn acute CRPS I, patients showed warm and cold hyperalgesia, indicated by significant changes in HPT and CPT. WDT and CDT were significantly increased as well, indicating warm and cold hypoaesthesia. In chronic CRPS, thermal hyperalgesia declined, but CDT as well as WDT further deteriorated. Solely patients with acute CRPS displayed PHS. To a minor degree, all QST changes were also present on the contralateral limb.ConclusionsWe propose three pathomechanisms of CRPS I, which follow a distinct time course: Thermal hyperalgesia, observed in acute CRPS, indicates an ongoing aseptic peripheral inflammation. Thermal hypoaesthesia, as detected in acute and chronic CRPS, signals a degeneration of A-delta and C-fibres, which further deteriorates in chronic CRPS. PHS in acute CRPS I indicates that both inflammation and degeneration are present, whilst in chronic CRPS I, the pathomechanism of degeneration dominates, signalled by the absence of PHS. The contralateral changes observed strongly suggest the involvement of the central nervous system.

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Background: The complex regional pain syndrome (CRPS) and fibromyalgia (FM) are chronic pain syndromes occurring in highly stressed individuals. Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. Methods: We performed a comparative study in 15 patients with CRPS type I, 22 patients with FM and 37 age- and sex-matched healthy controls and investigated the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes. Results: Lymphocyte numbers did not differ between groups. Quantitative analyses of lymphocyte subpopulations showed a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS (p < 0.01) and FM (p < 0.05) patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile. Conclusions: Future studies are warranted to answer whether such immunological changes play a pathogenetic role in CRPS and FM or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients.

Background In naive rats, corticosteroids activate neuronal membrane–bound glucocorticoid and mineralocorticoid receptors in spinal cord and periphery to modulate nociceptive behavior by nongenomic mechanisms. Here we investigated inflammation-induced changes in neuronal versus glial glucocorticoid and mineralocorticoid receptors and their ligand-mediated nongenomic impact on mechanical nociception in rats. Methods In Wistar rats (n = 5 to 7/group) with Freund’s complete adjuvant hind paw inflammation, we examined glucocorticoid and mineralocorticoid receptor expression in spinal cord and peripheral sensory neurons versus glial using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, immunohistochemistry, and radioligand binding. Moreover, we explored the expression of mineralocorticoid receptors protecting enzyme 11-betahydroxysteroid dehydrogenase type 2 as well as the nociceptive behavioral changes after glucocorticoid and mineralocorticoid receptors agonist or antagonist application. Results Hind paw inflammation resulted in significant upregulation of glucocorticoid receptors in nociceptive neurons of spinal cord (60%) and dorsal root ganglia (15%) as well as mineralocorticoid receptors, while corticosteroid plasma concentrations remained unchanged. Mineralocorticoid (83 ± 16 fmol/mg) but not glucocorticoid (104 ± 20 fmol/mg) membrane binding sites increased twofold in dorsal root ganglia concomitant with upregulated 11-betahydroxysteroid dehydrogenase type 2 (43%). Glucocorticoid and mineralocorticoid receptor expression in spinal microglia and astrocytes was small. Importantly, glucocorticoid receptor agonist dexamethasone or mineralocorticoid receptor antagonist canrenoate-K rapidly and dose-dependently attenuated nociceptive behavior. Isobolographic analysis of the combination of both drugs showed subadditive but not synergistic or additive effects. Conclusions The enhanced mechanical sensitivity of inflamed hind paws accompanied with corticosteroid receptor upregulation in spinal and peripheral sensory neurons was attenuated immediately after glucocorticoid receptor agonist and mineralocorticoid receptor antagonist administration, suggesting acute nongenomic effects consistent with detected membrane-bound corticosteroid receptors.

Clinical investigation is not reliable in the assessment of stellate ganglion blockade. Proof of sympathetically maintained pain based on pain relief after stellate ganglion blockade is not conclusive.