[Effectiveness of inpatient interdisciplinary multimodal pain therapy (IMPT) in patients with complex regional pain syndrome (CRPS) : A retrospective study]. / Wirksamkeit einer interdisziplinären multimodalen stationären Schmerztherapie (IMST) bei Patienten mit komplexem regionalem Schmerzsyndrom (CRPS) : Eine retrospektive Studie.

BACKGROUND: The primary symptom of complex regional pain syndrome (CRPS) is pain. Interdisciplinary multimodal pain therapy (IMPT) is the gold standard of treatment. The purpose of this study was to identify the beneficial effect of inpatient IMPT on pain level, sensation, perception and impairment in patients with CRPS. QUESTION: The aim of the present study was to examine the effect of full-term IMPT on pain intensity, pain perception, pain processing, and pain impairment in patients with CRPS. METHODS: In 265 patients with CRPS, pain level was retrospectively assessed by the numeric rating scale for pain (NRS), the Pain Perception Scale (SES) and the Pain Management Questionnaire (FESV) at the beginning and end of IMPT. RESULTS: There was a significant reduction in the average and highest pain level on the NRS, a significant improvement in the affective experience of pain and cognitive pain management, as well as pain-related mental impairment. All patients improved significantly in resting and relaxation techniques. With regard to pain-related helplessness and depression, patients with mental comorbidity benefitted most. Patients undergoing invasive procedures in the form of peripheral nerve blockage showed no significantly improved outcome with regard to the tested parameters. DISCUSSION: The current study demonstrated that IMPT has a highly beneficial effect on the level, experience and processing of pain in patients with CRPS.

Anti-Inflammatory Characteristics of Local Anesthetics: Inhibition of TNF-α Secretion of Lipopolysaccharide-Stimulated Leucocytes in Human Blood Samples.

Background. Local anesthetics (LAs) have potent anti-inflammatory properties. Inflammatory down-regulation is crucial in diseases with overactive immune reactions, such as acute respiratory distress syndrome (ARDS) and chronic inflammation. We investigated the influence of four LAs, procaine, lidocaine, mepivacaine, and bupivacaine, on the reduction of tumor necrosis factor-alpha (TNF-α) secretion in lipopolysaccharide (LPS)-activated human leucocytes. Methods. Blood samples of 28 individuals were stimulated with LPS. The reduction of TNF-α production by each of the four LAs added (0.5 mg/mL) was measured and correlated with biometric variables. A response was defined as reduction to <85% of initial levels. Results. All four LAs down-regulated the TNF-α secretion in 44−61%: Bupivacaine (44.4%), lidocaine (61.5%), mepivacaine (44.4%), and procaine (50% of the individuals, "responders"). The TNF-α secretion was reduced to 67.4, 68.0, 63.6, and 67.1% of the initial values in responders. The effects in both patients and healthy persons were the same. Interindividual responses to LAs were not correlated with the duration or type of complaints, basal TNF-α serum level, sex, BMI, or age of responders. Conclusions. Four clinically relevant LAs (amid-LA and ester-LA) attenuate the inflammatory response provoked by LPS. They are potential candidates for drug repositioning in treating overactive immune reactions and chronic inflammation.

Magnetic resonance imaging validation of medial transthyroid ultrasound-guided stellate ganglion block: A pilot study.

OBJECTIVE: Ultrasound-guided stellate ganglion block (usSGB) facilitates improved accuracy of needle position and application of lesser volumes of local anesthetic (LA). Approaches of usSGB, however, have not fully been optimized with respect to efficacy and technical convenience. This pilot study examined the anatomical position and spatial distribution of a small volume of LA injectate dispensed by medial transthyroid usSGB via magnetic resonance imaging (MRI) and assessment of its effect on cervical sympathetic nerves. METHODS: Twelve healthy males were tested in a double-blinded within-subject design. In a total of 37 usSGB, 3 ml of LA and saline 0.9% solution were injected intramuscularly into the longus colli muscle (LCM) preventing uncontrollable spread of LA within cervical structures. Immediately after injection, distribution of injectate was traced by MRI. Twenty-four out of the 37 usSGB-injections with 3 ml ropivacaine 1% (verum) and saline 0.9% (placebo) were compared. Efficacy of usSGB was assessed by the appearance of oculosympathetic paresis and increases in skin temperature. RESULTS: All usSGBs were positioned in the proximity of the LCM muscle belly. Most of the axial injectate was distributed within the transversal plane between the middle section of C5 and the upper section of T1 vertebra. Signs of oculosympathetic paresis and skin temperature increase were found exclusively under verum conditions. CONCLUSION: This pilot study demonstrated the feasibility of medial transthyroid usSGB using an out-of-plane technique and a volume of 3 ml of LA. Further studies are required to establish the relative value and safety of this technique compared to other published approaches.

Ethical Pain and Terminal Chaperonage.

Terminal chaperonage embedded in palliative care deeply resonates with human needs and has undergone significant advances in the past decades. At the same time, it is in jeopardy due to austerity measures in healthcare. Its comprehensive translation in philanthropic end-of-life practice necessitates reflection on underlying ethical issues. This chapter addresses ethical aspects arising in pain and terminal chaperonage and deduces important ethical imperatives in the wake of the palliative mandate. The imperatives affect the deployment of resources necessary for a humane pain and terminal chaperonage, one that is to be comprehensive and flexible in design and implementation at the same time. Furthermore, they are concerned with critical implications for dying clients emerging from the idiosyncratic properties of opioids with respect to their potential to induce mental status alterations. Given that living and dying are profoundly mental by nature, the human mind plays a fundamental role in the command of both. Based on this, this chapter also outlines the essentials of terminal thought plasticity and affect catharsis en route to a mindful, decent death. It identifies and advocates eight most fundamental affective, respectively cognitive fields of the human mind, the "Ensemble of the essential eight iridescent fields of relinquishment", whose adaptable, culturally sensitive facilitation in mental management prior to death may have to be considered the core ethical imperative in terminal chaperonage - in true congruence with philanthropic end-of-life care.

Effectiveness, Safety, and Predictive Potential in Ultrasound-Guided Stellate Ganglion Blockades for the Treatment of Sympathetically Maintained Pain.

BACKGROUND: Evaluating the effectiveness of stellate ganglion blockades (SGBs) proves challenging, since the criteria defining a successful blockade are controversial. This may be one reason for the scarcity of studies on this topic, thus forcing clinical guidelines to remain conservative in recommending SGBs. Moreover, factors to predict which patients will benefit from blockade series are not yet available. OBJECTIVES: The objectives of this study were to evaluate through a clinical approach SGBs' effectiveness performed under ultrasound guidance (us-SGB) and to identify factors to predict effectiveness. METHODS: We retrospectively analyzed 809 us-SGBs in 105 patients with complex regional pain syndrome (CRPS) and neuropathic pain syndromes (all potentially including sympathetically maintained pain) regarding pain reduction. Volume and type of local anesthetics, magnitude of pain, temperature of the dorsal hands, heart rate, blood pressure, and occurrence of Horner's syndrome or complications were assessed. RESULTS: Pain reduction after a blockade series was highly significant and showed no significant correlation with change of temperature, vital signs, or Horner's syndrome. For patients with neuropathic pain, the predictive potential for pain reduction following a blockade series lies within the range of pain reduction after the first blockade. In a literature comparison, incidences of complications (hoarseness 3.9%, dysphagia 3.4%, hematoma 0.6%) were lower than in non-ultrasound-guided techniques. CONCLUSIONS: Data indicate that us-SGBs are safe and effective in reducing sympathetically maintained pain in patients with CRPS and neuropathic pain syndromes. Pain reduction after the first blockade may predict total pain reduction after a blockade series. Other clinical measures seem unsuitable to predict effectiveness.

Cerebral sodium (23Na) magnetic resonance imaging in patients with migraine - a case-control study.

OBJECTIVE: Evaluation of MRI-derived cerebral 23Na concentrations in patients with migraine in comparison with healthy controls. MATERIALS AND METHODS: In this case-control study, 24 female migraine patients (mean age, 34 ± 11 years) were enrolled after evaluation of standardized questionnaires. Half (n = 12) of the cohort suffered from migraine, the other half was impaired by both migraine and tension-type headaches (TTH). The combined patient cohort was matched to 12 healthy female controls (mean age, 34 ± 11 years). All participants underwent a cerebral 23Na-magnetic resonance imaging examination at 3.0 T, which included a T1w MP-RAGE sequence and a 3D density-adapted, radial gradient echo sequence for 23Na imaging. Circular regions of interests were placed in predetermined anatomic regions: cerebrospinal fluid (CSF), gray and white matter, brain stem, and cerebellum. External 23Na reference phantoms were used to calculate the total 23Na tissue concentrations. Pearson's correlation, Kendall Tau, and Wilcoxon rank sum test were used for statistical analysis. RESULTS: 23Na concentrations of all patients in the CSF were significantly higher than in healthy controls (p < 0.001). The CSF of both the migraine and mixed migraine/TTH group showed significantly increased sodium concentrations compared to the control group (p = 0.007 and p < 0.001). Within the patient cohort, a positive correlation between pain level and TSC in the CSF (r = 0.62) could be observed. CONCLUSION: MRI-derived cerebral 23Na concentrations in the CSF of migraine patients were found to be statistically significantly higher than in healthy controls. KEY POINTS: • Cerebral sodium MRI supports the theory of ionic imbalances and may aid in the challenging pathophysiologic understanding of migraine. • Case-control study shows significantly higher sodium concentrations in cerebrospinal fluid of migraineurs. • Cerebral sodium MRI may become a non-invasive imaging tool for drugs to modulate sodium, and hence migraine, on a molecular level, and influence patient management.

Ultrasound-guided stellate ganglion blocks combined with pharmacological and occupational therapy in Complex Regional Pain Syndrome (CRPS): a pilot case series ad interim.

OBJECTIVE: This preliminary and retrospective pilot case series examines a treatment concept consisting of ultrasound-guided stellate ganglion blocks (SGBs) combined with pharmacological and occupational therapy in patients with complex regional pain syndrome (CRPS) of the hand. Efficacy of combined treatment concepts and safety of ultrasound-guided SGB have not been sufficiently investigated yet. METHODS: A total number of 156 blocks were evaluated in 16 patients with CRPS in a retrospective analysis. All patients received pharmacotherapy and a standard regimen of occupational therapy offered simultaneously to the SGBs. Changes in both spontaneous and evoked pain levels were assessed by numerical pain rating score before and after the last blockade of a series. Side effects were documented. RESULTS: The overall mean pain reduction was 63.2% regarding spontaneous and 45.3% regarding evoked pain. Mild complications, such as hoarseness or dysphagia, occurred in 13.5% of the blocks (21 SGBs). Serious complications, such as plexus paresis or accidental puncture of vessels or other structures, did not occur. Time between symptom onset and start of treatment did not affect the extent of pain reduction. CONCLUSIONS: The combination of ultrasound-guided SGB and simultaneous pharmacological and occupational therapy showed encouraging treatment results under conditions of this pilot case series. Assessment of efficacy of this combined treatment concept and safety of ultrasound-guided SGB require further prospective clinical studies with larger number of participants.

Comprehensive curriculum for phantom-based training of ultrasound-guided intercostal nerve and stellate ganglion blocks.

OBJECTIVE: Ultrasound (US)-guided pain procedures become increasingly important due to their numerous advantages. Solid proficiency is necessary, however, to minimize complications and guarantee adequate performance. To enable beginners to learn the relevant skills in the technique of US-guided stellate ganglion (SGB) and intercostal nerve block (ICB), a training curriculum was developed and tested using self-made phantoms. DESIGN: The curriculum comprised an introduction to the didactics of US, SGB, and ICB, a demonstration of the techniques by an expert user, as well as hands-on training of needle guidance using a gel pad and two phantoms. SUBJECTS: Three groups of participants with different levels of expertise with US-guided procedures took part in the curriculum: 12 medical students with no prior experience, 12 anesthesiologists with some experience, and five senior anesthesiologists who already applied these techniques on a regular basis. METHODS: Participants evaluated the curriculum via questionnaire, and their performance of time until adequate puncture, attempts required for adequate puncture, number of corrections, and unintentional punctures was assessed. RESULTS: The medical students significantly increased their speed during both nerve blocks and reduced the number of attempts and corrections necessary to perform adequate ICB. The anesthesiologists with some experience also increased their speed in both blocks. The participants rated the curriculum as good to very good. CONCLUSIONS: The combination of theoretical teaching, expert demonstration, and hands-on training on phantoms proved useful in acquiring skills needed for US-guided procedures such as SGB and ICB, and can potentially improve graduate and post-graduate medical education.

Synaptic scaffolding protein Homer1a protects against chronic inflammatory pain.

Glutamatergic signaling and intracellular calcium mobilization in the spinal cord are crucial for the development of nociceptive plasticity, which is associated with chronic pathological pain. Long-form Homer proteins anchor glutamatergic receptors to sources of calcium influx and release at synapses, which is antagonized by the short, activity-dependent splice variant Homer1a. We show here that Homer1a operates in a negative feedback loop to regulate the excitability of the pain pathway in an activity-dependent manner. Homer1a is rapidly and selectively upregulated in spinal cord neurons after peripheral inflammation in an NMDA receptor-dependent manner. Homer1a strongly attenuates calcium mobilization as well as MAP kinase activation induced by glutamate receptors and reduces synaptic contacts on spinal cord neurons that process pain inputs. Preventing activity-induced upregulation of Homer1a using shRNAs in mice in vivo exacerbates inflammatory pain. Thus, activity-dependent uncoupling of glutamate receptors from intracellular signaling mediators is a novel, endogenous physiological mechanism for counteracting sensitization at the first, crucial synapse in the pain pathway. Furthermore, we observed that targeted gene transfer of Homer1a to specific spinal segments in vivo reduces inflammatory hyperalgesia. Thus, Homer1 function is crucially involved in pain plasticity and constitutes a promising therapeutic target for the treatment of chronic inflammatory pain.

MRI verification of ultrasound-guided infiltrations of local anesthetics into the piriformis muscle.

OBJECTIVE: Patients presenting with buttock pain syndromes are common. Up to 8% of these conditions may be attributed to piriformis syndrome. Included in several therapeutic and diagnostic approaches, injections directly into the piriformis muscle may be performed. Because the muscle lies very close to neurovascular structures, electromyographic, fluoroscopic, computed tomographic, and magnetic resonance imaging (MRI) guidance have been employed. In few studies, an ultrasound-guided technique was used to inject a local anesthetic into the piriformis muscle without impairing adjacent neuronal structures. DESIGN: Feasibility study in healthy human subjects. Confirmation of ultrasound-guided injections by MRI. SUBJECTS: In 10 male human subjects, ultrasound-guided injections of 3 mL of a local anesthetic into the piriformis muscle were performed. METHODS: Directly after the injection, the subjects were placed in an MRI scanner, and the placement of the liquid depot was confirmed by MRI imaging. Somatosensory deficits were evaluated after the injection. RESULTS: The MRI showed that 9 of 10 of the injections were correctly placed within the piriformis muscle. The distance of the depot to the sciatic nerve decreased over time due to dispersion, but the nerve itself was not reached in the MRI. Only one subject experienced slight, short-term sensorimotor deficits. CONCLUSIONS: MRI confirmed the correct placement of the local anesthetic within the muscle. The dispersion of the fluid 30 minutes after the injection could be visualized. Moreover, only one subject experienced slight motor deficits without anatomical correlate. This ultrasound-guided method will be further employed in ongoing clinical studies.

Mechano-insensitive nociceptors are sufficient to induce histamine-induced itch.

The nerve fibres underlying histamine-induced itch have not been fully elucidated. We blocked the lateral femoral cutaneous nerve and mapped the skin area unresponsive to mechanical stimulation, but still sensitive to electrically induced pain. Nerve block induced significantly larger anaesthetic areas to mechanical (100 mN pin-prick, 402 ± 61 cm²; brush, 393 ± 63 cm²) and heat pain stimuli (401 ± 53 cm²) compared with electrical stimulation (352 ± 62 cm², p < 0.05), whereas the anaesthetic area tested with 260 mN (374 ± 57 cm²) did not differ significantly. Histamine was applied by iontophoresis (7.5 mC) at skin sites in which mechanical sensitivity was blocked, but electrical stimulation was still perceived 30 min after the nerve block (n = 9). In these areas iontophoresis of histamine provoked itching in 8/9 subjects with a mean maximum of 4.6 ± 1 (on an 11-point rating scale). Histamine-induced itch can thus be perceived at skin sites where input from mechano-sensitive polymodal nociceptors is blocked. In conclusion, input from mechano-insensitive nociceptors is sufficient to generate histamine-induced itch.

Quality of life and symptom evaluation in daily oncology practice: a survey of 150 patients with advanced gastrointestinal tumours receiving palliative chemotherapy.

BACKGROUND: Quality of life (QoL) is frequently investigated as a secondary endpoint in clinical trials but is rarely evaluated in clinical practice. The present survey sought to assess the QoL of patients with advanced gastrointestinal tumours receiving palliative chemotherapy. Furthermore, we wanted to compare the results of subscales of the generic EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, version 3.0) using assessment tools with an emphasis on pain and depression. PATIENTS AND METHODS: 150 patients with gastrointestinal tumours undergoing palliative chemotherapy completed 3 questionnaires. QoL was assessed using the EORTC QLQ-C30, Beck depression inventory (BDI) was utilised to measure the severity of patients' depression and a visual analogue scale (VAS) was applied to measure patient's pain intensity. Correlations between these assessments were calculated. RESULTS: The survey revealed that treatment of pain and depression appeared to be inadequate in the present cohort of patients with metastatic gastrointestinal cancer. Good correlations between EORTC QLQ-C30 subscales and the VAS (r = 0.86), as well as the BDI (r = 0.63) were found. CONCLUSION: The present analysis indicates the need for better symptom control regarding the examples 'pain' and 'depression'. In view of the good correlation between the EORTC QLQ-C30 and the BDI and VAS, further studies on the implementation of the EORTC QLQ-C30 as a screening tool, or for follow-up measurements in daily practice are warranted.

Therapy With Local Anesthetics to Treat Vulvodynia. A Pilot Study.

INTRODUCTION: Vulvodynia (chronic vulvar pain) is a sexually debilitating disorder with a prevalence of ∼10%. AIM: To investigate the effectiveness of therapy with local anesthetics (TLA) in women with severe vulvodynia, we conducted a prospective, non-controlled observational study. METHODS: 45 patients with severe chronic vulvodynia (primary and secondary vulvodynia, 0-10 numeric analogue scale (NAS) ≥6, median 7.9, duration ≥6 months, median 65.2 months) in an outpatient practice in Germany were treated with TLA in 3-12 sessions using procaine 1% as local anesthetic. Effectiveness was analyzed with Wilcoxon signed rank tests and Wilcoxon rank sum tests. OUTCOMES: Therapeutic success as a reduction of pain to ≤4 NAS lasting for ≥6 months after end of therapy. RESULTS: TLA successfully reduced vulvodynia in 36 of 45 patients (80 %, responders). The NAS reduction was from 7.9 to 2.4 (P < .001). Even patients denominated as non-responders experienced a significant reduction in NAS (P = .03). In responders, long-term success was observed for 6.8-125 months (median 24.1 months). No adverse events occurred. CLINICAL TRANSLATION: A promising new treatment for a hard-to-treat chronic female pain disorder. STRENGTHS AND LIMITATIONS: Limitation: Monocentric, non-controlled observational design; Strength: the high number of patients treated. CONCLUSION: The high success rate of TLA in this investigation offers new perspectives on the etiology of vulvodynia as a complex pain syndrome affecting several nerves of the pelvic floor, and also provides early insight into the effectiveness of TLA in women with vulvodynia. Weinschenk S, Benrath J, Kessler E, et al. Therapy With Local Anesthetics to Treat Vulvodynia. A Pilot Study. Sex Med 2022;10:100482.

Local hyperexcitability of C-nociceptors may predict responsiveness to topical lidocaine in neuropathic pain.

We explored whether increased C-nociceptor excitability predicts analgesic effects of topical lidocaine in 33 patients with mono- (n = 15) or poly-neuropathy (n = 18). Excitability of C-nociceptors was tested by transcutaneous electrical sinusoidal (4 Hz) and half sine wave (single 500 ms pulse) stimulation delivered to affected and non-affected sites. Analgesic effects of 24 hrs topical lidocaine were recorded. About 50% of patients reported increased pain from symptomatic skin upon continuous 4 Hz sinusoidal and about 25% upon 500 ms half sine wave stimulation. Electrically-evoked half sine wave pain correlated to their clinical pain level (r = 0.37, p < 0.05). Lidocaine-patches reduced spontaneous pain by >1-point NRS in 8 of 28 patients (p < 0.0001, ANOVA). Patients with increased pain to 2.5 sec sinusoidal stimulation at 0.2 and 0.4 mA intensity had significantly stronger analgesic effects of lidocaine and in reverse, patients with a pain reduction of >1 NRS had significantly higher pain ratings to continuous 1 min supra-threshold sinusoidal stimulation. In the assessed control skin areas of the patients, enhanced pain upon 1 min 4 Hz stimulation correlated to increased depression scores (HADS). Electrically assessed C-nociceptor excitability identified by slowly depolarizing electrical stimuli might reflect the source of neuropathic pain in some patients and can be useful for patient stratification to predict potential success of topical analgesics. Central neuronal circuitry assessment reflected by increased pain in control skin associated with higher HADS scores suggest central sensitization phenomena in a sub-population of neuropathic pain patients.

Differential sensory and clinical phenotypes of patients with chronic widespread and regional musculoskeletal pain.

The differentiation of chronic primary pain syndromes into those with widespread vs regional musculoskeletal pain has been characterized by controversial discussions about common or distinct mechanisms and core clinical and sensory criteria. For example, the recent revision of fibromyalgia criteria has discarded sensory characteristics such as number of "tender points." This study examined empirical evidence related to this diagnostic shift and aimed to identify basic sensory-clinical pain phenotypes in patients with chronic local primary pain (chronic primary back pain [CBP]) and patients with chronic widespread primary pain (fibromyalgia syndrome). Combined sensory-clinical pain phenotypes of 185 patients with previous CBP and fibromyalgia syndrome diagnoses were derived by a stepwise data reduction through descriptive statistical, correlational, principal components and latent class analyses. Clusters were cross-validated by linear discriminant analysis. Four clusters of patients were identified, requiring 4 pressure pain sensitivity markers (number of sensitive tender and control points, pain intensity, and pressure pain threshold at the trapezius) and 2 clinical pain characteristics (pain regions and present pain intensity). Subsequent discriminant analysis revealed that 3 discriminant functions of pressure sensitivity markers sufficed to differentiate the clusters. These sensory-clinical phenotypes differed also in somatic symptoms and impairment but neither in psychopathology nor in psychosocial cofactors. The results highlight the relevance of sensory testing in combination with clinical pain assessment in chronic primary pain syndromes.

Altered tactile localization and spatiotemporal integration in complex regional pain syndrome patients.

BACKGROUND: In complex regional pain syndrome (CRPS), altered perception of the affected hand and neglect-like symptoms of the affected body side are common features. In this study, we presented tactile stimuli to the affected hands in CRPS patients and matched healthy controls. METHODS: The participants' task was to point at the perceived positions of the stimuli using a tracking device. The spatial coordinates of the perceived positions were analysed for accuracy and consistency. We also presented patterns consisting of two stimuli at distinct positions with a delay of 100 ms. These patterns are known to induce spatiotemporal integration ("sensory saltation"). RESULTS: CRPS patients were less accurate and less consistent in the spatial perception of tactile stimuli on their hands. Furthermore, they showed increased spatiotemporal integration, although these effects were smaller than expected. These deficiencies were related to the clinically assessed intensity of recurrent pain episodes. Surprisingly, the intensity of clinically assessed ongoing pain was associated with increased precision. CONCLUSIONS: In line with earlier reports, our findings indicate that the representation of the affected hands in CRPS patients is less accurate than in healthy people, probably reflecting reorganization in somatosensory cortices. The exact relationships between these findings and other aspects of CRPS remain to be elucidated. SIGNIFICANCE: CRPS patients performed poorly in localizing positions on their affected hands via pointing and exhibited increased spatiotemporal integration. The presented method may prove useful in diagnostics as well as psychophysical and neurofunctional research on CRPS and other chronic pain disorders.

Deconstructing chronicity of musculoskeletal pain: intensity-duration relations, minimal dimensions and clusters of chronicity.

Background and aims Evaluating the degree to which pain has become chronic beyond mere duration poses several problems. The IASP Pain Taxonomy Axis IV employs intensity and duration combined to nine ordered categories. The Chronic Pain Grade links intensity and disability, but only the latter contributes to higher grades. The Mainz Pain Staging System includes temporal and spatial aspects, medication and health care utilization. Their interrelations, scale properties and construct validity are not always known or debatable. The study challenges the generality and homogeneity of the chronicity construct of musculoskeletal pain aiming at necessary and sufficient sub-constructs identified by separable marker clusters. We show chronicity to vary in content and structure with severity and duration and between different populations. This raises the question of validity conditions of general chronicity indices and requires further work on adequate chronicity measures. Methods Diagnostic entrance data of 185 patients with chronic regional vs. widespread musculoskeletal pain (unspecific back pain, fibromyalgia) from regional pain clinics and 170 active employees in a nationwide prevention program were included in a retrospective cross-sectional analysis of the combined marker sets of the three chronicity indices above. The samples of patients and employees provided intensity, duration and disability degrees over the whole range of the assumed chronicity. Intensity-duration relations were quantified by correlations and frequency distributions of successive duration classes. The dimensional structure of pain and chronicity variables was assessed by factor and cluster analyses. Results Pain intensity distributions showed inhomogeneous courses from short to long durations - lowest intensities predominating at longer durations in patients and at shorter in employees. Moreover, pain intensity and duration related nonlinearly to Chronic Pain Grade and Mainz Pain Stage and differently in patients compared to employees, and these indices correlated only moderately to each other. Factor and cluster analyses revealed different dimensions and clusters of chronicity markers for patients and employees. In the former, three dimensions with four clusters were identified with clinical characteristics (intensity, temporal and spatial aspects) separated from direct consequences (disability/interference with activities, medication usage) and chronic development (duration, healthcare utilization). In employees, only two dimensions with three clusters were obtained and clinical pain characteristics clustered with direct consequences both separated from chronic development. Similar differences were shown between unspecific back pain and fibromyalgia but were less well defined. Conclusions There appears to be no coherent "chronicity" entity over the entire range of severity and duration for all pain populations with different clinical pictures and social contexts. Statements about chronicity must be differentiated with respect to those aspects relative to patient career. Implications General indices do not capture the complex and changing composition of chronicity. There is evidence for at least three weakly coupled core domains of chronicity, i.e. the primary clinical characteristics, the direct consequences of current interference with activities, and aspects of the patient history. Hence, multivariate assessment is recommended. The particular syndrome, the diagnostic context and the population under investigation should likewise be considered.

Xenon blocks the induction of synaptic long-term potentiation in pain pathways in the rat spinal cord in vivo.

BACKGROUND: Xenon's (Xe) mechanisms for producing anesthesia and analgesia are not fully understood. We tested the effect of Xe equilibrated in a lipid formulation or normal saline on spinal C-fiber-evoked potentials and on the induction of synaptic long-term potentiation (LTP). METHODS: C-fiber-evoked field potentials were recorded in the superficial lumbar spinal cord in response to supramaximal electrical stimulation of the sciatic nerve. Anesthesia was maintained with isoflurane in one-third O2 and two-thirds N2O. Xe equilibrated at a concentration of 600 microL/mL of Lipofundin MCT(R) 20%, (n = 5) or solvent alone (n = 3), and Xe equilibrated at a concentration of 100 microL/mL of normal saline (n = 7) or saline alone (n = 7) was given IV under apnea. High-frequency stimulation of the sciatic nerve was applied 60 min after the injection of Xe-containing formulations or solvents [to induce LTP]. RESULTS: High-frequency stimulation potentiated C-fiber-evoked potentials to 156% +/- 14% (mean +/- sem) of control. Low-dose Xe in saline 0.9% blocked the induction of LTP. High-dose Xe equilibrated in MC(R) 20% showed no additional effect when compared with the solvent, which blocked the induction of LTP. CONCLUSION: Low-dose Xe in saline 0.9% revealed no antinociceptive, but preventive, action in spinal pain pathways.