Experimental muscle pain provokes long-lasting alterations of thermal sensitivity in the referred pain area.

This study explores thermal sensitivity and thermal nociception for signs of central sensitization in the area of referred muscle pain. Two groups of 24 healthy subjects (ss) each, and with mean ages of, respectively, 27 and 55 years, were first trained in quantitative sensory testing and pain rating. Then, in a second session, referred pain was evoked by injection of 6% hypertonic saline into the infraspinatus muscle. Cold and warm thresholds, synthetic heat threshold (SHT--evoked by an alternating pattern of adjacent cold and warmth), and thermal pain thresholds were measured within the referred pain area at a rate of 1/20 min for 60-120 min. All ss of both groups experienced referred pain mostly in the upper arm and of medium intensity. Pain lasted for approximately 12min with a shorter duration in the older group (p<0.02). The cold threshold increased significantly (p<0.001), and the warm threshold slightly, after the injection and remained high for the whole observation period (i.e. lower and higher temperatures were necessary to elicit cold and warmth, respectively). Threshold recovery was more delayed in the older age group. Of those 28 ss in whom cold pain threshold could be followed during the whole observation period, 18 ss showed an immediate threshold decrease of average 6 degrees C which outlasted the observation period. Four ss responded with a threshold increase. Heat pain thresholds were not affected in the referred pain area. Average synthetic heat threshold did not change; there were, however, distinct and lasting individual threshold shifts in either direction. Ss with lowered cold pain thresholds or evident threshold shifts for synthetic heat had also higher pain ratings. The results demonstrate that experimental muscle pain can induce long-lasting changes in thermal sensitivity and nociception. The unexpected cold threshold increase may tentatively be explained as an expression of long-term depression. The decrease of cold pain threshold or SHT in subgroups of ss may indicate central sensitization. However, the observed changes in this experiment do not provide an unambiguous indicator for central sensitization which seems to be rather individual and might depend on pain intensity and proneness to express central mechanisms of sensitization. Therefore in clinical pain states the individual pattern of sensory abnormalities has to be analysed and interpreted in addition to the pain parameters to assess central involvement.

von Frey hairs: new materials for a new design.

von Frey filaments are widely used in pain research. Conventionally, they are made of synthetic fibres. This plastic material is susceptible to changes in humidity and temperature, and such filaments do not keep their calibration. Filaments made of optical glass fibres are highly elastic and do not suffer these problems. Their optical properties can be used to make thin fibres more visible.

Thickness of the stratum corneum of the volar fingertips.

The thickness of the stratum corneum was measured by optical coherence tomography at the center and sides of the tactile elevations of all fingers in 87 healthy volunteers and 18 people with diabetes who performed regular glucose self-control. The cornified epidermis was thickest at the thumbs, and thickness decreased toward the little finger. The cornified epidermis was thinner at the sides of the tactile elevations than at the center, and it was thinner in women than in men. In people with diabetes, the cornified epidermis of the fingers most frequently used for capillary blood sampling was not conspicuously thickened.

Capillary blood sampling: the pain of single-use lancing devices.

Six disposable automatic lancing devices were examined in 50 healthy adult volunteers with regard to pain intensity, blood volume and user safety. Devices with a trigger-linked lancet movement were significantly more painful than those with a preset lancet speed. Residual pain was more frequent after the use of devices with a blade compared to devices with a needle. Only half of the devices reliably produced sufficient blood volumes (> 50 microl). Two of the devices could accidentally be re-used and constitute a hazard for patient and personnel. It is concluded that some of the disposable automatic lancing devices are safe and reliable but none of them causes minimal pain.

Capillary blood sampling: relation between lancet diameter, lancing pain and blood volume.

The relation between pain of capillary blood sampling and lancet diameter was studied in 52 healthy subjects. The tips of six fingers were pricked with a Softclix(R) II lancing device using lancets with identical facet geometry but needle diameters of 0.3, 0.4 and 0.8 mm. Two penetration depths (0.9 and 1.2 mm) were applied. Pain intensity and blood volume were recorded.At a puncture depth of 0.9 mm, pain did not differ between the three lancets. Pain increased with penetration depth, and at 1.2 mm the thicker lancets were somewhat more painful than the thinner ones. Blood volumes increased with lancet diameter and penetration depth. If the pain for punctures providing just enough blood for a glucose test (>/=10 µl) was compared, there was no difference between the lancets.It can be concluded that lancet diameter is of minor importance for the patient. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Reinnervation of split skin grafts in humans: comparison of two different methods of operation.

Studies on the reinnervation of split skin grafts have produced contradictory results. As the difference in sensitivity may be caused by the method of grafting, sensory reinnervation was studied in split skin grafted by two different methods. Thirty-nine patients given split skin grafts after the excision of malignant melanoma took part in the study. In 17 patients, split skin was grafted on to the intact muscle fascia. In another 22 patients the skin was grafted directly on to the muscle after the fascia had been removed. In all patients, sensitivity (to touch, heat/cold, and pain) was tested on the grafts and the skin from the opposite side. Sensory functions on grafted skin were generally reduced. Patients with split skin grafted on to the intact muscle fascia had better reinnervation than the ones in whom the fascia had been removed. However, individual patients from both groups showed surprisingly good reinnervation of transplanted skin. The reasons for this finding are not clear, but it is quite possible that the characteristics of the grafted skin have some influence on the reinnervation.

Daily variations of functional parameters and density distribution in human blood platelets.

Blood platelets play a critical role in the onset of myocardial infarction, which has been shown to have a circadian rhythmicity with a peak incidence in the morning. In an attempt to correlate platelet parameters with the outcome of cardiovascular diseases, we studied the daily (24-h) variation of the following platelet parameters: distribution pattern of functional heterogeneous platelet subpopulations; serotonin uptake; ketanserin binding; aggregation upon thrombin, serotonin, and ADP stimulation; and platelet count. Furthermore, we analyzed the tryptophan and serotonin concentrations in the blood samples. The percentage of less dense platelets, which represent the subpopulation with the highest preactivation, showed a rhythmicity period of 24 h and an acrophase at 21:18 h. The time course of intermediate and high density platelets was inverse to that of low density platelets. The serotonin uptake exhibited also a rhythmicity with a 24-h period. The acrophase was at 13:50 h. The aggregation curves were inverse to the ketanserin binding curves. The serotonin concentration exhibited a 12-h rhythmicity. The results obtained suggest that (a) changes in platelet activity are reflected by several parameters of platelet function that underlie daily variations; (b) the aggregation curves show a peak in the morning, with an additional peak in the afternoon; and (c) changes in the distribution pattern occur independently from variations in platelet functions like aggregation and serotonin binding.

Dose-response relation of ornipressin with regard to vasoconstriction in human skin.

We have studied the vasoconstrictor potency of ornipressin in the skin of 30 volunteers. Subjects received intradermal injections (50 microliters) of five different concentrations of ornipressin (10(-4) - 10(0) u. ml-1 in 0.9% saline) and plain 0.9% saline as a control. Immediately before injection, basal cutaneous blood flow in the test field was enhanced with 1% histamine. Capillary flux was measured by laser Doppler flowmetry and the size of pallor was determined. Ornipressin was effective at 10(-4) u. ml-1 and had its largest constrictor effect at concentrations of 10(-2) and 10(-1) u. ml-1. Larger concentrations were less effective in reducing capillary flux. Interindividually, the most effective concentration varied between 10(-3) and 10(-1) u. ml-1. The size of pallor grew in a dose-dependent manner but 10(0) u. ml-1 always caused reddening in its centre. Capacitance vessels (skin colour) were more sensitive to ornipressin than resistance vessels (capillary flux). The shortest latency of vasoconstriction was obtained with concentrations of 10(-2) and 10(-1) u. ml-1. The results of this study suggest that for haemostasis of the skin a concentration of ornipressin 10(-2) u. ml-1 is useful; this low concentration would reduce total dosage and unwanted side effects.

Effects of intradermal lignocaine and mepivacaine on human cutaneous circulation in areas with histamine-induced neurogenic inflammation.

The vasoconstrictive potencies of lignocaine and mepivacaine were studied in human skin. Lignocaine 0.5%, 0.25% mepivacaine (both plain and mixed with adrenaline or ornipressin), and saline (control) were injected intradermally into skin areas with enhanced perfusion (1% histamine prick). Flux was determined by scanning laser Doppler flowmetry and the size of any eventual pallor was measured. The artificially enhanced flux was increased further by saline, but not altered by the local anaesthetics. Mepivacaine produced a small pallor. Both vasoconstrictors reduced flux significantly and produced a larger pallor. We conclude that both local anaesthetics have only a mild constrictive effect on precapillary vessels. Mepivacaine has, additionally, a constrictor effect on the postcapillary vascular bed, causing pallor. An effective precapillary constriction which reduces the capillary clearance of both local anaesthetics can be achieved only by addition of a vasoconstrictor.

[A simple technique for estimating the level of analgesia in regional anesthesia]. / Ein einfaches Verfahren zur Abschätzung der Analgesiegrenzen in der Regionalanaesthesie.

In regional anesthesia the onset of analgesia is usually determined by stimulating the skin with sharp or cold objects: when sensations of sharp pain or cold are lost, all nociceptive afferents are regarded as blocked. Sharp pain and cold are mediated by thin, myelinated axons whereas the majority of nociceptor axons are unmyelinated. In peripheral nerve blocks unmyelinated fibers are blocked first, followed by those mediating sharp pain and cold. In spinal and epidural blocks the levels of anesthesia to sharp pain and cold correspond within 1-2 segments. Although pinprick seems to be a simple test for analgesia, it involves the risk of infection and is disliked by the patient. As the stimulus is spatially discontinuous, coarse testing may simulate analgesia. An ideal stimulus for testing analgesia should be noninvasive, give distinct sensations, not frighten the patient, and allow spatially continuous examination of larger skin areas. A stimulus that meets these conditions is cold applied to the skin by a metal roller (Fig. 1). If the roller is kept at room temperature (20 degrees-24 degrees C), it gives a strong cold sensation when it is slowly rolled (5-10 cm/s) over the warm skin (usually 30 degrees-35 degrees C on the trunk). With this noninvasive device, the levels of anesthesia to cold can be determined rapidly, with high precision, and without frightening the patient.

Automatic scanner for multi-point laser Doppler flux recordings on human skin.

A computer-driven device is described which moves the probes of a laser Doppler flowmeter linearly back and forth over the skin and stops precisely at preselected points to measure capillary perfusion. It offers extended possibilities to record the spatio-temporal flux changes in response to a local stimulus (e.g. injection of a vasoactive substance).

[Cutaneous blood flow following subcutaneous infiltration of lidocaine with and without the addition of adrenaline or ornipressin]. / Hautdurchblutung nach subkutaner Lidocain-Infiltration mit und ohne Zusatz von Adrenalin oder Ornipressin.

The addition of ornipressin to local anesthetics increases the duration of regional anesthesia. A dose of 0.1 unit/ml produces an increase in nerve block duration comparable to adrenaline 5 micrograms/ml. In order to suppress intraoperative bleeding higher concentrations of ornipressin have been used in infiltration anesthesia. This study was designed to examine whether an increase in ornipressin concentration above 0.1 unit/ml causes a further reduction in cutaneous blood flow. Twelve volunteers took part in the study. They received intracutaneous infiltrations of 4 ml lidocaine 0.5% in the volar aspects of both forearms (Fig. 1). The solution was either plain (= Lido) or contained adrenaline 5 micrograms/ml (Lido + A), or ornipressin 0.1 unit/ml (Lido + P1) or 0.2 unit/ml (Lido + P2). Blood flow was measured with a laser Doppler flowmeter; before the infiltration the skin was locally heated to 40 degrees C in order to obtain maximal perfusion (Flow 100); this temperature was maintained throughout the measuring period. The minimal flow after infiltration was calculated as a percentage of Flow 100. Lido caused a significant decrease in flow to 59 +/- 25% (M +/- SD). Lido + A, Lido + P1 and Lido + P2 caused further significant flow reductions, to 19 +/- 21%, 23 +/- 16% and 26 +/- 23%, respectively (Figs. 3, 4). The latency of maximal flow reduction did not differ between the four solutions (Fig. 5). The results show that in infiltration anesthesia an increase in ornipressin concentration above 0.1 unit/ml does not improve superficial vasoconstriction.

Local anesthetic efficacy of ropivacaine (LEA 103) in ulnar nerve block.

Ropivacaine (LEA 103) is a new long-acting local anesthetic that in animal experiments has proved to be equally potent but less toxic than bupivacaine. In this controlled double-blind study in man, the dose-response relation of ropivacaine was examined in peripheral nerve block and its potency was compared to that of bupivacaine. Nerve functions during bilateral ulnar nerve block were monitored in 70 normal subjects by a computer-controlled method. Results indicate that plain ropivacaine is optimally effective at concentrations between 0.5% and 0.75%, where it reliably blocks nerve functions for about 8 hours. Its profile of action is uniform for the different fiber groups and resembles that of bupivacaine. Addition of epinephrine does not improve latency or duration of ropivacaine nerve block. Adverse effects attributable to ropivacaine have not been observed.

Effects of daytime noise load on the sleep-wake cycle and endocrine patterns in man: I. 24 hours neurophysiological data.

This study examines the influence of daytime noise load on the spontaneous EEG activity during wakefulness and sleep. Twelve healthy male subjects participated in two experimental series, each consisting of three consecutive nights and the two days in between. EEG, EOG, EMG, ECG and respiration were continuously recorded. During one series from 9:00 to 21:00 h the subjects were exposed to 85 dB(A) industrial noise. Direct effects of the noise exposure were a slight blockade of the alpha and theta activity; towards the evening, when self-estimated tiredness was high, increased alpha and beta power were found (p less than .01). Aftereffects on subsequent undisturbed night sleep were a reduction in REM sleep (p less than .001), shortened sleep cycles (p less than .01) and an increase in slow wave sleep during the 2nd sleep cycle (p less than .05). These results are interpreted as signs of strained wakefulness and intensified fatigue, as disturbance of sleep processes and as an intensified need for recovery.

Daytime noise stress and subsequent night sleep: interference with sleep patterns, endocrine and neurocrine functions.

The effects of strong daytime noise stress on subsequent undisturbed night sleep were studied in six male volunteers. They slept for seven consecutive nights in the laboratory, two nights being preceded by an 8 h exposure to 83 dB (A) pink noise. Continuously during all nights EEG, EOG, EMG, ECG and respiration were recorded. Additionally, during five nights, blood samples were taken every 30 min by an indwelling venous catheter for the determination of ACTH, hGH, PRL, TRP, 5-HT and 5-HIAA. After daytime noise load, increased sleep stage 4 stability, partly elevated hGH and PRL levels and decreased levels of the metabolites of the serotonergic system were found. This result may be explained by the assumption that high daytime noise stress is an additional load for the CNS which demands an intensification of recovery processes during the sleep of the subsequent night.

[Addition of muscle relaxants to intravenous regional anesthesia]. / Zusatz von Muskelrelaxantien zur intravenösen Regionalanaesthesie.

Nine volunteers received two intravenous regional anaesthetics in the right arm. The first anaesthetic was performed with plain 0.25% lignocaine (dose 1 ml/kg body weight), the second with the same volume of lignocaine, with the addition of 0.5 mg pancuronium-Bromide. Latency for onset of the following was measured in both groups: 1. analgesia, 2. cold sensation, 3. warm sensation, 4. touch, 5. motor blockade. As expected, the addition of pancuronium had no influence on sensory blockade, however, motor block was significantly stronger, faster in onset, and longer in duration. Significant systemic side effects after pancuronium were not observed. No pancuronium was found in flame photometry plasma studies. On the basis of these investigations, one can recommend, for I.V.R.A., a relatively large volume of dilute local anaesthetic solution and, to achieve better muscle relaxation, the addition of 0.5 mg of pancuronium.

Daytime noise and subsequent night sleep in man.

The effects of daytime noise on recovery processes during subsequent undisturbed night sleep were studied in six healthy men (21-27 years), exposed to 80 dB (A) pink noise 8 h per day for 2 days. Sleep EEG, ECG, and respiration were recorded in the laboratory for five consecutive nights: two baseline nights, two nights following noise stimulation, and again one baseline night. Additionally questionnaire data were collected, reflecting a subjective impairment of the recovery function of sleep after noise exposure. EEG sleep data of the first post-noise night showed an increase in slow wave sleep with a simultaneous decrease in stage 2 sleep. During the second post-noise night these changes were less prominent. Three subjects additionally showed an instability in the sleep course coinciding with elevated heart and respiration rates. However, altogether the autonomic parameters were not clearly affected by the noise exposure. The findings support the assumption that strong daytime noise may interfere with subsequent sleep processes.

[Comparative studies of the local anaesthetic action of carticaine 1% and mepivacaine 1% (author's transl)]. / Vergleichende Untersuchung über die Wirkung von Carticain 1% und Mepivacain 1%.

The actions of carticaine 1% and mepivacaine 1% in peripheral nerve block were investigated in double-blind study. Bilateral ulnar nerve blocks were performed in 14 healthy subjects (age range 20-30 years), and latency, duration, and intensity of anaesthesia were quantitatively determined. There were no differences in latency of nerve block, but a significant difference in the duration of effect: Mepivacaine acted for nearly twice as long as Carticaine. In addition, several incomplete blocks were noted with Carticaine. On the basis of these results mepivacaine is preferred in peripheral nerve block because of its longer and more reliable action.