Sensory profiles in women with neuropathic pain after breast cancer surgery.

PURPOSE: We performed a detailed analysis of sensory function in patients with chronic post-surgical neuropathic pain (NP) after breast cancer treatments by quantitative sensory testing (QST) with DFNS (German Research Network on Neuropathic Pain) protocol and bed side examination (BE). The nature of sensory changes in peripheral NP may reflect distinct pathophysiological backgrounds that can guide the treatment choices. NP with sensory gain (i.e., hyperesthesia, hyperalgesia, allodynia) has been shown to respond to Na+-channel blockers (e.g., oxcarbazepine). METHODS: 104 patients with at least "probable" NP in the surgical area were included. All patients had been treated for breast cancer 4-9 years ago and the handling of the intercostobrachial nerve (ICBN) was verified by the surgeon. QST was conducted at the site of NP in the surgical or nearby area and the corresponding contralateral area. BE covered the upper body and sensory abnormalities were marked on body maps and digitalized for area calculation. The outcomes of BE and QST were compared to assess the value of QST in the sensory examination of this patient group. RESULTS: Loss of function in both small and large fibers was a prominent feature in QST in the area of post-surgical NP. QST profiles did not differ between spared and resected ICBN. In BE, hypoesthesia on multiple modalities was highly prevalent. The presence of sensory gain in BE was associated with more intense pain. CONCLUSIONS: Extensive sensory loss is characteristic for chronic post-surgical NP several years after treatment for breast cancer. These patients are unlikely to respond to Na+-channel blockers.

[Botulinum toxin A injections in neuropathic pain : A post-hoc subgroup analysis of patients with peripheral nerve injury]. / Botulinumtoxin-A-Injektionen bei neuropathischem Schmerz : Eine Post-hoc-Subgruppenanalyse bei Patienten mit peripherer Nervenverletzung.

The randomized controlled trial (RCT) presented in this article showed significant relief in neuropathic pain following subcutaneous injections of botulinum toxin A over 24 weeks compared to placebo. This result was confirmed in a novel post-hoc analysis of the subgroup of 46 patients with peripheral nerve injury. Relevant adverse effects did not occur during the RCT.

Explorative sensory profile evaluation in central neuropathic pain following spinal cord injury.

BACKGROUND: Sensory profiling in neuropathic pain using quantitative sensory testing (QST) has not been extended to central neuropathic pain due to spinal cord injury (SCI). This study aims to fill this gap by evaluating sensory profiles in patients with neuropathic SCI pain. METHOD: We retrospectively analysed consecutive QST data from 62 patients with neuropathic spinal cord injury pain (SCIP), following the German Research Network on Neuropathic Pain protocol. The study included at-level and below-level SCIP due to a spinal cord lesion, and at-level SCIP following a cauda equina lesion. QST parameters were compared between diagnostic groups. QST profiles of below-level SCIP (central neuropathic pain) were manually assigned to sensory phenotypes based on literature and expert opinion. RESULTS: No statistical difference in QST parameters between pain diagnoses was found. For central neuropathic pain (below-level SCIP), three phenotypes were descriptively observed: loss of function (59%), thermal and mechanical hyperalgesia combination (16%), and mechanical hyperalgesia (19%). The remaining 5% of patients did not fit a common pattern. There was no statistical difference in clinical and psychological variables between phenotypes. In a subgroup analysis, the loss of function phenotype weakly correlated with older age, longer time since injury, and longer pain duration. CONCLUSIONS: Here, we capture sensory phenotypes of central neuropathic pain following SCI. The limited sample size, high rate of missing values, and the retrospective nature of the study mean that results should be seen as strictly exploratory. Further research should replicate these findings and explore the significance of phenotypes. SIGNIFICANCE STATEMENT: The evaluation of sensory phenotypes by quantitative sensory testing in central neuropathic pain due to SCI adds a new perspective on sensory phenotypes in comparison to peripheral neuropathic pain. The described thermal and mechanical hyperalgesia combination might represent involvement of the spinothalamic tract. In addition, there was a trend towards older age and longer time since injury in patients with loss of function.

Opioid intake prior to admission is not increased in elderly patients with low-energy fractures: A case-control study in a German hospital population.

BACKGROUND: Recent studies revealed an increased prescription rate of opioids for elderly patients suffering bone fractures. To gain further insight, we conducted face-to-face interviews in the present study to compare the opioid intake between patients with low-energy fractures and patients suffering from internal diseases. METHODS: In this case-control study, 992 patients, aged 60 years and older, were enrolled between March 2014 and February 2015. The interview comprised a fall and medication history, comorbidities, mobility and other risk factors for fractures. Odds ratios (OR) and a multiple logistic regression model were calculated. RESULTS: The number of patients with pre-admission opioid intake in the last 12 months was comparable in the fracture (n = 399, 13.3%) and the control group (n = 593, 14.7% OR: 0.89, CI: 0.62-1.29). The number of patients with current opioid intake of short duration (<3 months) was similar in both groups (14% vs. 20%; OR: 0.66, CI: 0.23-1.93). Patients with opioid intake in the fracture group reported more frequently fatigue as an adverse event of opioid medication (58% vs. 30%; OR: 3.32, CI: 1.48-7.45). Patients with opioid intake showed more severe comorbidities and significantly decreased mobility compared to those without opioids. CONCLUSION: Elderly patients internalized due to low-energy fractures did not take opioids more frequently than patients with internal admission, for both short (<3 months) and longer duration intake. Patients with opioid intake were generally in poorer physical condition. The risk of fracture might increase in patients suffering from fatigue as a side effect of opioid medication. SIGNIFICANCE: This study is based on face-to-face interviews with patients, including details about side effects and fracture history, providing a more pronounced picture of the relation of opioid intake and risk of fracture.

Conditioned pain modulation using painful cutaneous electrical stimulation or simply habituation?

BACKGROUND AND AIMS: Cold pressor test was recently reported to significantly reduce painful cutaneous electrical stimulation (PCES)-induced pain and corresponding evoked potentials (PCES-EPs), but whether this reduction is an effect of conditioned pain modulation (CPM) remains unknown. To what extent these findings are confounded by habituation is also unknown. We thus compared the effect of CPM and habituation on PCES-induced pain and PCES-EPs and analysed whether increased attention by a random change of electric stimulation would intensify this possible habituation effect. METHODS: Three custom-built concentric surface electrodes were used to induce a pain intensity of 60 on a 0-100 numerical rating scale (NRS) among 29 healthy subjects (age 20-35y, 16 females). PCES-EPs (including P0N1 and N1P1 amplitudes, N1 latencies) were assessed over Cz. Group A received 14 min of electrical stimulation with constant intensity followed by 14 min of electrical stimulation with variable intensities, group B vice versa. Afterwards, subjects perceived cold-water pain (10 °C) contralaterally as conditioning stimulus to assess CPM. Statistical analysis was conducted with ANOVA and t-test. RESULTS: In both groups, N1 latencies remain unchanged, but the intensity of PCES-induced pain (12 ± 17%; p < 0.01) and N1P1 amplitudes of PCES-EPs (10 ± 16%; p < 0.05) decreased significantly during the 14-min PCES with constant current intensity. CPM also significantly reduced pain ratings (36 ± 19%; p < 0.001) and amplitudes (37.2 ± 15.8%), p < 0.001). A significant decline of P0N1 amplitudes occurred only during CPM (18 ± 61%; p < 0.001). CONCLUSION: We found a significant effect of habituation on PCES-induced pain and PCES-EPs, although the effect of CPM was significantly larger and could not be explained by habituation alone. SIGNIFICANCE: Painful cutaneous electrical stimulation leads to moderate habituation of pain and evoked potential amplitudes, but the conditioned pain modulation effect using this method is significantly larger, which might indicate a different mechanism in central processing.

Recovery of mechanical detection thresholds after direct digital nerve repair versus conduit implantation.

The purpose of this study was to assess sensory and functional nerve recovery after digital nerve injury in patients with an end-to-end suture (S) or with implantation of a collagen conduit (C) to bridge a nerve gap. Fifteen S and 11 C with a follow-up of 6-36 months and 28 healthy control participants were enrolled. Methods of assessments were quantitative sensory testing, the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), range of motion and the painDetect questionnaire. After both procedures, sensory profiles showed largely recovered function of C and Aδ fibres but severe loss of Aß-fibre function leading to increased mechanical detection thresholds. There was only minimal allodynia. Severe pain was absent. Patients with conduits reported more functional impairment, especially in work performance, which correlated with the assessed loss of Aß-fibre function. LEVEL OF EVIDENCE: III.

Unimpaired endogenous pain inhibition in the early phase of complex regional pain syndrome.

BACKGROUND: The complex regional pain syndrome (CRPS) is characterized by distal generalisation of pain beyond the initial trauma. This might be the result of impaired endogenous pain inhibition. METHOD: We compared Conditioned Pain Modulation (CPM) between patients with CRPS (n = 24; pain: 4.5 ± 2.2, NRS 0-10; disease duration <1 year), neuralgia (n = 17; pain: 5.5 ± 1.1) and healthy subjects (n = 23) and its correlation with loss and gain of function as assessed by Quantitative Sensory Testing (QST). CPM was assessed with heat as test stimulus (TS) and cold water as conditioning stimulus (CS). The early CPM-effect was calculated as difference between heat pain during and before conditioning, the late CPM-effect, 5 minutes after and before conditioning, respectively. RESULTS: Heat pain decreased comparably after CS in all groups, resulting in a significant CPM-effect (healthy: -12.5 ± 12.4, NRS 0-100; CRPS: -14.7 ± 15.7; neuralgia: -7.9 ± 9.8; p < 0.001). When compared to healthy subjects, heat pain declined significantly steeper in CRPS patients (healthy: -2.0 ± 5.5, NRS 0-100/10 s; CRPS: -6.3 ± 8.1; p < 0.05). Only CRPS patients demonstrated a late CPM effect (-6.0 ± 9.0, p < 0.005). Neither spontaneous pain nor any QST parameter correlated with CPM, with the exception of a decreased cold pain threshold, which correlated with an enhanced CPM in CRPS patients only (r = -0.456, p < 0.05). CONCLUSION: An impairment of endogenous pain inhibition does not explain the extent of pain in the early stage of CRPS or in neuralgia. The unexpectedly high CPM in CRPS patients might result from activation of the intact descending pathways in response to central sensitization, as cold hyperalgesia correlated with the CPM-effect. SIGNIFICANCE: Conditioned pain modulation (CPM) is not impaired in the early phase of complex regional pain syndrome (CRPS) and neuralgia. Only in CRPS higher CPM was associated with lower cold pain thresholds.

Remote ischaemic conditioning decreases blood flow and improves oxygen extraction in patients with early complex regional pain syndrome.

BACKGROUND: Remote ischaemic conditioning (RIC) is the cyclic application of non-damaging ischaemia leading to an increased tissue perfusion, among others triggered by NO (monoxide). Complex regional pain syndrome (CRPS) is known to have vascular alterations such as increased blood shunting and decreased NO blood-levels, which in turn lead to decreased tissue perfusion. We therefore hypothesized that RIC could improve tissue perfusion in CRPS. METHOD: In this proof-of-concept study, RIC was applied in the following groups: in 21 patients with early CRPS with a clinical history less than a year, in 20 age/sex-matched controls and in 12 patients with unilateral nerve lesions via a tourniquet on the unaffected/non-dominant upper limb. Blood flow and tissue oxygen saturation (StO2 ) were assessed before, during and after RIC via laser Doppler and tissue spectroscopy on the affected extremity. The oxygen extraction fraction was calculated. RESULTS: After RIC, blood flow declined in CRPS (p < 0.01). StO2 decreased in CRPS and healthy controls (p < 0.01). Only in CRPS, the oxygen extraction fraction correlated negatively with the decreasing blood flow (p < 0.05). CONCLUSION: Contrary to our expectations, RIC induced a decrease of blood flow in CRPS, which led to a revised hypothesis: the decrease of blood flow might be due to an anti-inflammatory effect that attenuates vascular disturbances and reduces blood shunting, thus improving oxygen extraction. Further studies could determine whether a repeated application of RIC leads to a reduced hypoxia in chronic CRPS. SIGNIFICANCE: Remote ischaemic conditioning leads to a decrease of blood flow. This decrease inversely correlates with the oxygen extraction in patients with CRPS.

Lipoprotein-associated phospholipase A2 for early risk stratification in patients with suspected acute coronary syndrome: a multi-marker approach: the North Wuerttemberg and Berlin Infarction Study-II (NOBIS-II).

AIMS: Numerous markers have been identified as useful predictors of major adverse cardiac events (MACE) in patients with suspected acute coronary syndrome (ACS). However, only little is known about the relative benefit of the single markers in risk stratification and the best combination for optimising prognostic power. The aim of the present study was to define the role of the emerging cardiovascular risk marker lipoprotein-associated phospholipase A2 (Lp-PLA2) in a multi-marker approach in combination with troponin I (TnI), NT-proBNP, high sensitivity (hs)CRP, and D-dimer in patients with ACS. METHODS AND RESULTS: A total of 429 consecutive patients (age 60.5+/-14.1 years, 60.6% male) who were admitted to the emergency room with suspected ACS were analysed in the study. Biochemical markers were measured by immunoassay techniques. All patients underwent point-of-care TnI testing and early coronary angiography if appropriate, in accordance with the current guidelines. Classification and regression trees (CART) and logistic regression techniques were employed to determine the relative predictive power of markers for the primary end-point defined as any of the following events within 42 days after admission: death, non-fatal myocardial infarction, unstable AP requiring admission, admission for decompensated heart failure or shock, percutaneous coronary intervention, coronary artery bypass grafting, life threatening arrhythmias or resuscitation. The incidence of the primary end-point was 13.1%, suggesting a mild to moderate risk population. The best overall risk stratification was obtained using NT-proBNP at a cut-off of 5000 pg/mL (incidence of 40% versus 10.3%, relative risk (RR) 3.9 (95% CI 2.4-6.3)). In the remaining lower risk group with an incidence of 10.3%, further separation was performed using TnI (cut-off 0.14 microg/L; RR=3.1 (95% CI 1.7-5.5) 23.2% versus 7.5%) and again NT-proBNP (at a cut-off of 140 ng/L) in patients with negative TnI (RR=3.2 (95% CI 1.3-7.9), 11.7% versus 3.6%). A final significant stratification in patients with moderately elevated NT-proBNP levels was achieved using Lp-PLA2 at a cut-off of 210 microg/L) (17.9% versus 6.9%; RR=2.6 (95% CI 1.1-6.6)). None of the clinical or ECG variables of the TIMI (Thrombolysis In Myocardial Infarction) risk score provided comparable clinically relevant information for risk stratification. CONCLUSIONS: In the setting of stateof- the-art coronary care for patients with suspected ACS in the emergency room, NT-proBNP, troponin I, and Lp-PLA2 are effective independent markers for risk stratification that proved to be superior to the TIMI risk score. Lp-PLA2 turned out to be a more effective risk marker than hsCRP in these patients.

[Music as adjuvant therapy for coronary heart disease. Therapeutic music lowers anxiety, stress and beta-endorphin concentrations in patients from a coronary sport group]. / Musik als begleitende Therapie bei koronarer Herzkrankheit. Therapeutische Musik verringert Angst, Stress und beta-Endorphinkonzentrationen bei Patienten einer Herzsportgruppe.

BACKGROUND: In a study with coronary patients it was estimated that music is able to lower stress and fear and contributing to relaxation in spite of physical exercise. PATIENTS AND METHODS: 15 patients (13 male, two female, mean age 62,2 +/- 7,6 years) of a coronary sport unit were listening to an especially composed relaxation music while training their common heart-frequency adapted exercises. Before the exercises and after listening to music blood pressures were measured and blood was collected for determination of beta-endorphin. Simultaneous to blood collection the participants had to perform two psychometric test: the perceived stress experience questionnaire (PSQ) of Levenstein to measure the graduation of subjective perceived stress and the state-anxiety inquiry (STAI) of Spielberger as an indicator of coping. To practice the trial ("test trial"), the whole protocol was performed one week prior to the mean trial, but without listening to music and without blood collections and blood pressure measurements. RESULTS: In the test trial without music there were no significant changes in PSQ-data. In the mean trial, under the influence of music, values in the section "worries" decreased as a sign of lower worries (26.6 versus 27.6; p = 0.039). STAI-values were significantly lower as a sign of reduced fear after listening to music (31 versus 34; p = 0.045). beta-endorphin concentration (10.91 microg/l versus 15.96 microg/l, p = 0.044) and systolic blood pressure (130 mmHg versus 140 mmHg; p = 0.007) decreased significantly after listening to music. CONCLUSIONS: Regarding worries and fear, patients seemed to benefit by the intervention of music. beta-endorphin was lowered significantly after music despite physical activity.

Immediate physiological responses of healthy volunteers to different types of music: cardiovascular, hormonal and mental changes.

A group of 20 healthy volunteers [10 women, 10 men; median age 25 (20-33) years] were examined by means of pulsed wave Doppler echocardiography, blood sample analysis and psychological testing before and after listening to three different examples of music: a waltz by J. Strauss, a modern classic by H. W. Henze, and meditative music by R. Shankar. To assess small haemodynamic changes, mitral flow, which reflects left ventricular diastolic behaviour, was measured by Doppler ultrasound. Heart rate, arterial blood pressure and plasma concentrations of adrenocorticotropic hormone, cortisol, prolactin, adrenaline, noradrenaline, atrial natriuretic peptide (ANP) and tissue plasminogen activator (t-PA) were determined simultaneously. Transmitral flow profile is characterized by early E-wave and late atrial induced A-wave. Velocity-time integrals were measured and the atrial filling fraction was calculated. The mental state was measured by using a psychological score (Zerssen) with low values (minimum 0) for enthusiastic and high values (maximum 56) for depressive patterns. Music by J. Strauss resulted in an increase of atrial filling fraction (AFF; 29% vs 26%; P < 0.05) and ANP (63 pg.ml-1 vs 60 pg.ml-1; P < 0.05). The mental state was improved (Zerssen: 6.5 vs 11 points; P < 0.05). After the music of H. W. Henze prolactin values were lowered (7.7 ng.ml-1 vs 9.1 ng.ml-1; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Stress reduction through listening to music: effects on stress hormones, hemodynamics and mental state in patients with arterial hypertension and in healthy persons]. / Stressreduktion durch Musikhören. Einfluss auf Stresshormone, Hämodynamik und psychisches Befinden bei Patienten mit arterieller Hypertonie und bei Gesunden.

Stress hormones, tissue-plasminogen activator (t-PA) antigen, left-ventricular diastolic function and mood immediately before and after listening to three different kinds of music (a waltz by J. Strauss, a piece of modern classic by H. W. Henze, and meditative music by R. Shankar) were measured in 20 healthy persons (10 women, 10 men; mean age 25 [20-33] years) and 20 hypertensives (8 women, 12 men; mean age 57.5 [25-72] years). To recognise haemodynamic effects, mitral flow by Doppler ultrasound was used as a measure of left-ventricular diastolic function. Atrial filling pressure (AFF) was calculated from the flow integral (VTI) of the early E and the late A waves. The Zerssen scale was used to estimate the immediate mood of the subjects. In hypertensives the levels of cortisol (74 vs 78 ng/ml; P < 0.05) and t-PA antigen (4.3 vs 4.5 ng/ml; P < 0.05) were lower after than before the Strauss waltz. The muscle by Henze lowered the concentrations of cortisol (70 vs 84 ng/ml; P < 0.05), noradrenaline (203 vs 224 ng/l; P < 0.05) and t-PA antigen (4.1 vs 4.6 ng/ml; P < 0.05). After listening to the piece by Shankar the concentrations of cortisol (71 vs 78 ng/ml; P < 0.05), adrenaline 14.5 vs 24.5 ng/ml; P < 0.05) and t-PA antigen (4.2 vs 4.3 ng/ml; P < 0.05) were lower. In healthy subjects AFF (29 vs 26%; P < 0.05) rose after the Strauss music, VTI-E fell (69 vs 73 mm; P < 0.05, while natriuretic peptide rose (63 vs 60 pg/ml; P < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)