Startseite Cerebral oxygenation for pain monitoring in adults is ineffective: A sequence-randomized, sham controlled study in volunteers
Artikel Öffentlich zugänglich

Cerebral oxygenation for pain monitoring in adults is ineffective: A sequence-randomized, sham controlled study in volunteers

  • Christine H. Meyer-Frießem EMAIL logo , Gunnar Jess , Esther M. Pogatzki-Zahn und Peter K. Zahn
Veröffentlicht/Copyright: 1. Juli 2017
Artikel downloaden (PDF)
Veröffentlichen auch Sie bei De Gruyter Brill
Informationen für Autor*innen Erkunden Sie dieses Fachgebiet
Scandinavian Journal of Pain
Aus der Zeitschrift Scandinavian Journal of Pain Band 16 Heft 1

Abstract

Background

Pain assessment by Numeric Rating Scale (NRS) is considered to be good clinical practice, but objective pain assessment is still a challenge. Near infrared spectroscopy (NIRS) measures cerebral tissue oxygen saturation (SctO2) that increases with cortical-neuronal activity and may provide point-of-care bedside pain monitoring. Analogous to promising studies in newborns, we hypothesize that different levels of SctO2 can probably quantify pain intensity. SctO2 may increase following painful in contrast to non-painful or sham stimuli and may correlate with pain intensity as assessed by NRS in volunteers.

Methods

Twenty healthy male students (24.2±1.9 years), recruited via local advertising, were consecutively included in a sequence-randomized, sham-controlled, single-blinded study. SctO2 was recorded continuously with two NIRS sensors on the forehead. After resting, four stimuli were applied in a random order on the right forearm (unexpected and expected electrical pain, expected non-painful and sham stimuli). Blinded subjects were asked to rate each stimulus on NRS. Statistics: RM-ANOVA; Wilcoxon or paired Student t-test; Spearman’s rank correlation; P < .05.

Results

Resting volunteers showed SctO2 of 72.65%±3.39. SctO2 significantly increased for about 60 to 70s until a maximum after unexpected painful (74.62%±3.9; P = .022) and sham stimuli (74.07%±3.23; P =.014). Expected painful (P =.139) and non-painful stimuli (P =.455) resulted in no changes in SctO2. NRS scores (median, IQR) were rated significantly higher after expected (5.25, 3.5 to 6.75) than after unexpected (4.5, 3 to 5; P = .008) pain. No strong correlation was found between NRS and SctO2.

Conclusions and Implications

Contrary to our expectations, measuring SctO2 via a two-channel NIRS is not able to remediate the lack of objective bedside pain assessment under standardized experimental conditions in alert adults.

Keywords: Pain monitoring; Cerebral oxygen saturation; NIRS; Near infrared spectroscopy; SctO2

1 Introduction

Point-of-care diagnostics are at the focus of research for many years. Pain intensity assessment by Numeric Rating Scale (NRS) is considered to be good clinical practice, but objective assessment remains still a challenge, because bedside pain monitoring is still lacking.

For example, only conscious patients can score their pain on one-dimensional scales, such as the NRS. Pain ratings via scales are more or less subjective and not directly comparable between individuals. Vegetative signs like sweating or tears, heart rate (HR) or blood pressure (BP) are not sensitive and are non-specific for their use under clinical conditions. [1] Additionally, various parameters such as heartbeat intervals, heart rate variability, plethysmographic pulse wave amplitude, surgical stress index, skin conductance, pupillary dilatation reflex and electroencephalographic measures have been investigated, with controversial results. [2,3,4,5,6,7,8]

Cortical haemodynamic response may be an alternative and more central related measure of pain processing compared to behavioural or physiological measures. Cerebral oximetry, based on near infrared spectroscopy technology (NIRS), measures local concentrations of oxy-(HbO2) and deoxy-haemoglobin (Hb) and provides regional cerebral tissue oxygen saturation (SctO2) that increases with cortical-neuronal activity [9,10,11]. A two-channel NIRS is a widely used, non-invasive device [12] that can be used, for example, to reduce adverse clinical outcomes during cardiovascular surgery [13,14].

Promising studies of newborns have reported changes in somatosensory and frontal cortex activation, particularly in cerebral oxygenation measured by NIRS as a result of altered haemodynamic activity, after nociceptive procedures [15,16,17,18,19]. Additionally, functional NIRS (fNIRS) could differentiate signal changes of both innocuous and noxious stimuli in the primary somatosensory cortex contralateral to the stimulus in healthy subjects [20]. In sedated patients scheduled for heart surgery, increased SctO2 values in the frontal cortex were observed during low nociceptive procedures [21]. Furthermore, in a pilot study of alert humans, a pain- and itch-related activation pattern of SctO2 in the prefrontal cortex was determined using a multichannel-topography [22].

To our knowledge, cerebral oxygenation using a portable two-channel NIRS for bedside pain monitoring has never been investigated in alert adults under standardized, sham-controlled conditions. We hypothesize that different levels of SctO2 can probably quantify pain intensity. Therefore, we designed a randomized, placebo-controlled study exposing alert volunteers to experimental painful, non-painful and sham stimuli. We postulate that SctO2 increases following painful stimuli in contrast to non-painful and sham stimuli and that it correlates with stimulus intensities and pain ratings via NRS in volunteers.

2 Materials and methods

This single-blinded, sequence-randomized cross-over study was conducted with volunteers upon receiving written consent. The study protocol was approved by the local Ethics Committee of the Faculty of Medicine of the Ruhr University Bochum, Germany (Chairman: Prof. Dr. M. Zenz; Gesundheitscampus 33, 44801 Bochum, Germany; No. 4501-12; date of approval: 23 Oct 2012). The experimental procedure was in accordance with the Declaration of Helsinki and the manuscript adheres to the applicable Equator guidelines.

2.1 Subjects

The study recruited male subjects (mean age 24.2±1.9 years) via local advertising starting on 2 January 2013. All 20 consecutively included participants were right handed and healthy. Volunteers with any anamnestic disorders or who had received medical consultation in the previous six months and those who were taking regular medication or who had exposure to medications for analgesia in the previous three months were excluded. Subjects were not aware of the study hypothesis.

2.2 Cerebral oximetry

Cerebral oximetry by means of near infrared spectroscopy provides information on the availability of oxygen in brain tissue [23]. It measures continuous local concentrations of oxy- and de-oxygenated haemoglobin and regional cerebral tissue oxygen saturation (SctO2) at the microvascular level [24]. Usually, it presents a mixed oxygen saturation and reflects a proportional mix of arterial (∼30%) and venous (∼70%) blood in the outlying regions of the brain [25]. SctO2 is defined as a ratio of oxygenated haemoglobin and total haemoglobin (HbT) concentrations in brain tissue (SctO2 = 100%×HbO2/(Hb + HbO2). It non-invasively reflects regional cerebral metabolism and the balance of local cerebral oxygen supply and demand. Near infrared light (absorption spectra 770 to 910 nm) from a FORE-SIGH™ Cerebral Oximeter (MC-2030, CAS Medical Systems, Inc., Branford, U.S.A.) penetrates the brain to measure mostly grey matter in the frontal cortex region [26], and absolute values are updated every 2 s (s) on the monitor (ratio arterial to venous blood 70/30). Displayed in a range from 0 to 99% are SctO2 levels for the right (R-SctO2) and left (L-SctO2) hemispheres and averaged for both as SctO2 in general. SctO2 increases with cortical-neuronal activity due to cerebral vasodilatation with an increase in cerebral blood volume [9,10,11,26] or decreases, for example, due to oxygen deficiency.

2.3 Study design

All volunteers, participating in a single session, lay on their backs in a darkened and silent laboratory and were asked to shut their eyes. All subjects were told that four painful stimuli would be applied after a warning and that they would rate the pain level after each stimulus between 0 and 10 (0 = no pain, 10 = most intense pain imaginable) on NRS. The use of decimal scores was permitted.

Two standard single-use NIRS sensors were placed on the right and left sides of the adult forehead after skin defatting. A self-made electrode consisting of 12 pins was fixed 5 cm distal to the crook of the right ventral arm. A painful electrical stimulus of 2 mA was administered there for 5 s at 100 Hz with a constant-current stimulator (DS7A, Digitimer, Welwyn Garden City, UK). [8]

The session started with a baseline measurement for 5 min without any disturbance to adjust to the situation (pre-Base 1). Next, four different stimuli were successively applied. See Fig. 1. For each subject, the first stimulus was an electrical unexpected painful stimulus (UPS) that was against the expectation given without warning. The next stimulus was an electrical expected painful stimulus (EPS) or a neutral non-painful stimulus (NPS) or a placebo stimulus (PS). All subsequent stimuli were given in a previously generated computer-based random order (six different order options) at ‘0s’, each following a repeated announcement, within a latency time of 30 s. EPS was set with identical intensity to UPS, but was announced beforehand. Except the unexpected first stimulus, all stimuli were preceded by a warning and expected to be painful due to the instruction given at the beginning. The NPS consisted of a spray of disinfectant on the right ventral forearm and after announcement of placebo stimulus, no stimulus was given at all. Between two stimuli, there was a resting phase of 5 min: 0 to 150 s recovery time, followed by a new baseline for 150 s for the next stimulus. All data were analyzed offline.

Fig. 1 Experimental setup. UPS, unexpected electrical pain; EPS, expected electrical pain; NPS, expected non-painful stimulus; PS, expected sham stimulus. Each stimulus (EPS/NPS/PS/UPS) was set at ‘0 s’. UPS was always the first stimulus. Awarning (W) was given between ‘−30 to 0 s’ before EPS, NPS and PS of random order. Pre-base 1 is the overall base at the beginning of all measurements. Post-base and pre-base 2 might be identical before and after the different stimuli.
Fig. 1

Experimental setup.

UPS, unexpected electrical pain; EPS, expected electrical pain; NPS, expected non-painful stimulus; PS, expected sham stimulus. Each stimulus (EPS/NPS/PS/UPS) was set at ‘0 s’. UPS was always the first stimulus. Awarning (W) was given between ‘−30 to 0 s’ before EPS, NPS and PS of random order. Pre-base 1 is the overall base at the beginning of all measurements. Post-base and pre-base 2 might be identical before and after the different stimuli.

2.4 Data and statistical analysis

The FORE-SIGHT™ Cerebral Oximeter recorded an averaged SctO2, R-SctO2 and L-SctO2 every 2 s. Our data revealed consistently higher values for R-SctO2 than for L-SctO2. To simplify, we therefore reported the bifrontal SctO2 of predetermined observational time intervals. Each stimulus (UPS, EPS, NPS or PS) was set at ‘0 s’ and the time count started again. There were two different baselines prior to the stimuli. Pre-base 1 was the overall base at the beginning of all measurements prior to UPS at ‘−300 to 0 s’. Pre-base 2 was the base at the beginning of EPS, NPS or PS at ‘−180 to −30 s’. Pre-base 1 was used as a reference baseline for all calculations. The warning was given verbally 30 s before the stimuli (‘−30 to 0 s’).After each stimulus the observational period was divided into different time intervals of about 30 s. Afterwards, a baseline was again recorded, called post-base ‘150 to 300 s’. Post-base and pre-base 2 could be identical before and after a consecutive stimulus. End-base was measured at the end of the last measurement. Observational periods and durations of the sessions were determined after five pilot measurements under comparable study conditions.

Quantitative data (SctO2 means, amplitudes, maxima, minima, slopes, NRS) are presented as mean (M) with standard deviation (±SD) and median (Md) with interquartile range (IQR). Amplitudes were measured between maxima and minima of the SctO2 within the particular intervals. The SctO2 slope for comparing SctO2 time courses was set between two SctO2 values at 0, 30, 60, 90, 120 and 150s.

Statistical Package for Social Sciences (SPSS) software (Version 22, IBM, Chicago, IL, USA) was used for analysis. Data were checked for normal distribution using the Shapiro–Wilk test. SctO2 is considered as a ratio scale. For the comparison of NRS values (UPS vs. EPS) and time in s until reaching SctO2 maxima following a painful or non-painful stimulus, a Wilcoxon signed rank test or a paired Student’s t-test was used. Quantitative SctO2 data were first analyzed using a two-way analysis of variance (ANOVA) for repeated measurements (rm) to test only for main effects (‘stimulus’ [UPS, EPS, NPS, PS] and ‘time’ [different time intervals]). A post hoc one-way rmANOVA was performed to compare SctO2 values ‘across different stimuli’ and for comparison across ‘time intervals for each stimulus’. Additionally, tests for sequence and sequence × stimulus interactions as part of the cross-over analysis were performed. Greenhouse–Geisser and Bonferroni adjusted P values are reported as appropriate. The Spearman’s rank correlation coefficient (rs) was used to assess the associations between NRS values and time to reach SctO2 maxima in s vs. SctO2 maxima. UPS and EPS were grouped as painful, whereas NPS and PS were grouped as non-painful stimuli. A two-sided P value <.05 was considered statistically significant.

Fig. 2 Boxplot of pain intensity after electrical stimuli. n = 20. NRS, numerical rating scale (0 = no pain, 10 = most intense pain imaginable): UPS, unexpected electrical pain; EPS, expected electrical pain. EPS: Md = 5.25, IQR 3.5 to 6.75, UPS: Md = 4.5, IQR 3 to 5; Z = -2.66, P = .008).
Fig. 2

Boxplot of pain intensity after electrical stimuli. n = 20. NRS, numerical rating scale (0 = no pain, 10 = most intense pain imaginable): UPS, unexpected electrical pain; EPS, expected electrical pain. EPS: Md = 5.25, IQR 3.5 to 6.75, UPS: Md = 4.5, IQR 3 to 5; Z = -2.66, P = .008).

3 Results

All 20 subjects were consecutively included in data analysis. See Table 1. None complained of any adverse effects from NIRS electrodes or after application of electrical stimuli. HR and BP varied within normal reference values and showed no changes during measurements.

Table 1

Clinical data and results of measurements of study population.

Characteristic (n = 20)
Male sex, n 20
Right-handedness, n 20
Age, y, mean ± SD 24.2 ± 1.91
BMI (kg/m2), mean ± SD 22.0 ± 2.15
HR (bpm), mean ± SD 66.1 ± 10.3
BP (mmHg), mean ± SD 133/69 ± 9.21/9.15
HbT Baseline right, mean ± SD[*] 69.02 ± 8.11
HbT Baseline left, mean ± SD[*] 71.47 ± 8.08
SctO2 Baseline right (%), mean ± SD 73.17 ± 2.92
SctO2 Baseline left (%), mean ± SD 72.02 ± 4.11
NRS (0–10) UPS 4.3 ± 1.7
NRS (0–10) EPS 5.0 ± 2.0
NRS (0–10) NPS 0.1 ± 0.3
NRS (0–10) PS 0 ± 0

  1. BMI, body mass index; HR, heart rate; BP, blood pressure; NRS, numeric rating scale; EPS, expected electrical pain stimulus; NPS, expected non-painful stimulus; PS, expected, sham stimulus; UPS, unexpected electrical pain; SD, standard deviation; HbT, total haemoglobin.

3.1 Pain rating

Pain intensity scores after expected painful stimuli were rated 6.8% higher than compared to unexpected stimuli of equal strength (Z =2.66, P = .008). See Fig. 2. Five volunteers considered the NPS slightly painful, but all assessed the PS with 0 on NRS. See Table 1.

3.2 SctO2 time courses

In the resting state, alert volunteers presented SctO2 values of 72.65% (±3.39) bilaterally. This pre-base 1 did not differ from pre-base 2 (72.95% ±3.34; t(59) = −1.764, P = .083) or end-base (72.99%±3.26; t(19) = −.832, P =.416). Additionally, the post-base (72.99 ± 3.26) was comparable to the overall base (72.87% ± 3.34; t(79) = 1.055, P =.295). The R-SctO2 pre-base 1 showed mean values of 73.17% (±2.92); in general, the left side showed lower values (72.02%±4.11; t(19) = −2.225, P =.038). As this significant difference could be observed for all conditions we concentrated on bifrontal SctO2.

Main effects of stimulus (F(1.88) = 3.45, P =.049), time (F(1.89) = 4.46, P =.008) and the interaction between stimulus and time (F(3.79) = 3.04, P =.003) were observed. Tests for sequence interactions as part of the cross-over analysis showed no influence (F(18.97) = .804, P =.692). Post hoc tests revealed that SctO2 increased significantly and continuously to a maximum between ‘60 to 90s’ after the application of UPS (74.62%±3.9; F(1.31) = 5.28, P =.022) and PS (74.07%±3.23; F(1.93) = 4.89, P = .014). After UPS 17 out of 20 subjects (85%) showed an increase of SctO2 between ‘60 to 90 s’ (3 non-responders (15%)), only 12 subjects (60%) showed this increase after EPS.

The pure warning prior to EPS, NPS or PS had no effect on the SctO2 (F(1.465) = .486, P =.562). The significant increase in SctO2 after UPS and PS occurred with a latency of at least 30 s. There was a maximal increase of 3.4% compared to pre-base 1 for UPS and 2.05% for PS. SctO2 maxima following UPS (75.12%±3.58) and PS (74.14%±3.29; t(19) = 3.153, P =.005) were reached after 59.95 s (±15.82) and 69.3 s (±16.71), respectively (t(19) = −1.732, P =.10). The sharpest rise was observed between ‘30 to 60 s’ for UPS and between ‘60 to 90 s’ for PS. There was no significant difference in SctO2 slopes between stimuli conditions. A decrease back to baseline was observed 3 to 5 min following UPS and PS. EPS (F(1.83) = 2.12, P =.139) and NPS (F(1.997) = .803, P =.455) showed no relevant effects on SctO2 over time. Post hoc tests revealed higher SctO2 for UPS than for EPS and NPS over time (P < .004). See Fig. 3. Minima, maxima and amplitudes of SctO2 revealed comparable results, as shown above on means for all conditions.

3.3 Correlation between SctO2and NRS

There was no correlation between the SctO2 maxima and the NRS of UPS (rs = .35, P =.22) or EPS (rs = .109, P = .648) in the interval ‘30 to 60 s’. See Fig. 4. Furthermore, there was a mild positive correlation between the SctO2 slope in the time interval of steepest rise and the NRS of UPS (rs = .530, P = .016) but no correlation between the time to reach the SctO2 maxima and the NRS of UPS (rs = .256, P = .277).

Fig. 3 Effects on SctO2 time courses following different stimuli. Data are presented as mean (M) and standard error of mean (SEM) for n = 20. The x-axis presents time intervals in s after each stimulus set at ‘0’. SctO2 reached the maximum by an average of 60s after UPS and 70s after PS. UPS, unexpected electrical pain; EPS, expected electrical pain; NPS, expected non-painful stimulus; PS, expected sham stimulus. ANOVA forrepeated measurements comparing time intervals between 0 and 120s following each stimulus: *P < .05. ANOVA for repeated measurements comparing UPS vs. EPS: • P < .05 and UPS vs. NPS: ♦ P < .05.
Fig. 3

Effects on SctO2 time courses following different stimuli.

Data are presented as mean (M) and standard error of mean (SEM) for n = 20. The x-axis presents time intervals in s after each stimulus set at ‘0’. SctO2 reached the maximum by an average of 60s after UPS and 70s after PS. UPS, unexpected electrical pain; EPS, expected electrical pain; NPS, expected non-painful stimulus; PS, expected sham stimulus. ANOVA forrepeated measurements comparing time intervals between 0 and 120s following each stimulus: *P < .05. ANOVA for repeated measurements comparing UPS vs. EPS: • P < .05 and UPS vs. NPS: ♦ P < .05.

4 Discussion

For the first time, SctO2 was monitored by a two-channel NIRS to investigate its predictive value for pain intensity rating in a standardized experimental pain setup conducted with alert volunteers. As anticipated, SctO2 increased after unexpected painful stimuli. However, contrary to our hypothesis, this did not differ from SctO2 curves after sham stimulation that was preceded by warning and expected to be painful but no pain was applied in fact. Similarly, neither pure warnings prior to painful (EPS) and non-painful stimuli (NPS) nor the stimuli themselves caused any differences in SctO2. Furthermore, no strong correlations were found between pain intensity ratings on NRS and changes in SctO2.

Cortical haemodynamic response may provide a more objective measure of central pain processing compared to either behavioural or physiological measures. Measuring the functional activation of the brain, NIRS is a widely used, non-invasive method to assess SctO2 in different clinical conditions [13,14,27,28,29,30,31]. SctO2 increases with cortical-neuronal activity due to activity induced cerebral vasodilatation with an increase of cerebral blood volume and blood flow [9,10,32].

An increasing number of studies investigated pain-induced NIRS responses during the past years. In newborns, HbT rises within 20 s after a heel laceration [17]. The authors postulated a clear distinction between spinal reflex response and cortical processing because non-painful stimuli with a von-Frey hair did not lead to any cortical activation [17]. In preterm newborn infants, unilateral tactile or painful stimuli elicited bifrontal increases in cortical HbO2 concentrations within somatosensory cortical areas persisting over at least a 60s-period with a latency of 2 s [15]. A stronger NIRS response occurred after venepuncture than after skin disinfection [15], and skin-to-skin contact between premature infants and their mothers showed a significantly smaller increase in HbO2 on the contralateral side after venepuncture [33]. In a pilot study, increased SctO2 values in adults were observed during low nociceptive procedures [21]. The researchers failed to find significant correlations between SctO2 and self-reported pain intensity [21], but painful-stimuli were influenced by premedication with morphine and midazolam. Including seven alert subjects, a gradual increase of HbO2 to a peak in the prefrontal cortex at approximately 19s using a multichannel device was observed after nociceptive stimulation with a force gauge at digital tip with an increasing intensity, leading to a reduction back to baseline [22].

In our well controlled study exposing alert volunteers to experimental painful, non-painful and sham stimuli effects (with and without expectation) cortical HbO2 concentrations increased under almost all conditions. Unexpected pain provokes the highest increase from baseline in SctO2 with the shortest latency. But sham condition (a poor expectation of experiencing a painful stimulus) increased cortical HbO2 concentration similar to real stimulation in alert volunteers.

Many brain regions are involved interactively in the perception of pain, including the somatosensory cortex, the frontal cortex, the insula, the anterior cingulate cortex and the thalamus [34]. fMRI suggests that healthy newborn babies experience some aspects of pain in a similar way to adults [35], so it should be suitable to compare newborns and adults. NIRS tends to be more accurate in newborns because the light penetrates better, and in premature babies, can even be transmitted. Thus, differences between newborns and adults might be due to a more temporal electrode placement on heads of newborns and the fact that the 2.5 cm depth monitoring covered a much larger fraction of the total brain in newborns than in adults. Extracranial influences of adults might change NIRS signals in an unknown extent.

Most striking, even L-SctO2 was consistently lower compared to the right hemisphere our results showed a bifrontal activation of the cortex detected as an increase in cerebral tissue oxygenation by NIRS. This is despite of the fact that all volunteers were right handed and were stimulated on the right forearm. However, this is controversially to previous results as pain specific bilateral or contralateral cortical activation was found in newborns and infants aged between 25 and 45 weeks postmenstrual [15,17]. Following the bifrontal activation of SctO2, we support the assumption that the induced cortical response is a generalized effect on the cortex of affective activation after painful stimulation. While fMRI measures an increase in blood flow (increase of circulation), which changes as a result of local neuronal activity (e.g. activated by pain), our key hypothesis is based on a general stronger increase of cerebral oxygen delivery compared to an oxygen demand during pain perception. Thus, a correlation between a general pain activation and an oxygen delivery-demand balance in a superficial non-specific area of the frontal brain might be imaginable.

Our study gives rise for a non-pain specific increase of SctO2 in awake adults assessed by a two-channel NIRS. Individual emotions, such as inner tension and surprise, are probably the most important confounding factors of SctO2 changes in awake adults. The same bifrontal increase in SctO2 was seen in response to painful stimulation that was unexpected (UPS) and the expectation of a painful stimulus that did not happen (PS). Under both conditions, an unexpected event occurred, and the NIRS response was similar. Thus, sympathetic activation due to unexpected events rather than pain caused the NIRS response in our setting. This assumption is in line with an unpleasant emotion that is accompanied by an increase in SctO2 in the bilateral prefrontal cortex in students or that O2Hb levels correlate with anxiety in the right frontal region in volunteers [36]. Indeed, the pure forewarning about a pain stimulus to follow did not lead to an increase in SctO2 in the next 30 s in our study. On the contrary, the announced and finally applied painful stimulus (EPS) was in line with the expectations of the volunteers, because they had already experienced this electrical pain once before and so the SctO2 did not change except of normal haemodynamic oscillation; likewise, the non-painful spray of disinfectant (NPS) did not influence the SctO2 probably due to a feeling of relief. In conclusion, we should consider that neuronal activity measured in response to transient nociceptive stimulation in awake adults is likely to be largely unspecific for nociception [37], which might explain once more the differences of our results to the studies of newborns [15,16,17,18,19].

4.1 Limitations

Following fNIRS studies NIRS [20,38], one limitation in our study might be the two-channel NIRS device itself that is limited in the depth of measurements of only 2.5 cm. SctO2 levels may be different in deeper brain structures, may vary due to brain atrophy [30] and may be different due to electrode positions. The use of only two optodes may limit studying responses to painful stimuli that simultaneously involve multiple areas of the brain [39]. It likely would be better to position the electrodes at the bilateral parietal head more close to the somatosensory cortices (which may be more difficult with hairy subjects) as done partly in the newborn studies [15,16,17,18,19]. However, the actual aim of our study was to investigate a point-of-care method that monitors pain intensity at bedside with two self-adhesive sensors as a non-invasive, inexpensive method with an easy handling, positioning and interpretation.

Furthermore, the majority of previous studies investigating NIRS for pain assessment presented data on HbO2, HHb or HbT. The used device measures HbT but only presents calculated SctO2 levels. However, the measured total haemoglobin (HbT) concentrations is not validated according to the manufacturer’s statement, is presented without SI-units and therefore could not be included in the statistical analysis. Multichannel devices that directly measure HbO2 might provide more precise results [15].

As the electrical noxious stimulus was rated as moderate, an inadequate stimulus, as recorded previously [21], can be neglected. In the present study, NRS values were higher after the expected pain stimulus compared to the unexpected pain stimulus. In particular, the influence of pain expectation is likely to be very important in this kind of experimental setup [40]. From an ethical point of view, we had to inform the subjects about using electrical pain stimuli. That alone may cause a certain expectation. Nevertheless, to be able to study the issue of SctO2 after unexpected and expected pain, the first stimulus was administered without announcement. This may have strengthened the volunteers’ attention and thus causing a cortical avoidance posture for pain. So the EPS might be rated higher in reality. Additionally, our experimental applied electrical pain stimulus, which was not calibrated according to its nature, might be only partly comparable with a clinical pain situation of ongoing nociceptive pain (e.g. acute postoperative pain).

We chose a uniform, homogenous, same-sex [41] healthy populationn– without non-modifiable characteristics that influence the SctO2 baseline [42] – using a standardized study protocol without the disturbance of noise or light. However, confounding factors – for example, abrupt movement caused by the application of a stimulus – might have affected the SctO2 curves. Further research should be performed by varying the study design: number and location of the electrodes should probably be changed, there should be a larger sample size with regard to a potentially large intra- and inter-individual variability in SctO2 and clinical studies on patients should be performed. Furthermore, variations in SctO2 levels should be investigated in sedated or anesthetized patients for pain monitoring [21] isolated from an emotional subjective pain experience as has been shown successfully using skin conduction. [43] This is underlined by the rate of 40% of non-repsonders (i.e. lack of an increase of SctO2 after EPS) compared to a non-announced pain stimulus which is probably less mental influenced. In other words, the stronger the emotional influence was (i.e. announcement of pain stimulus), the more subjects did not react with an increase of SctO2 as expected.

Probably, we have measured not directly pain but its sympathetic response and affective component cortically represented inter alia in the frontal cortex. Here, changes in SctO2 are most likely influenced by emotions, such as expectation and surprise, in alert adult volunteers.

Fig. 4 Scatter plot of SctO2 maxima following painful stimuli and NRS pain intensity. A Spearman’s rank correlation coefficient (rs) was computed to assess the relationship between SctO2 maxima (‘30 to 60s’) and NRS after painful stimuli (UPS and EPS).There was no correlation betweenthe two variables (rs = .04, P =.805). Regression lines are plotted forconvenience. n = 40, UPS, unexpected electrical pain; EPS, expected electrical pain; NRS, numerical rating scale.
Fig. 4

Scatter plot of SctO2 maxima following painful stimuli and NRS pain intensity.

A Spearman’s rank correlation coefficient (rs) was computed to assess the relationship between SctO2 maxima (‘30 to 60s’) and NRS after painful stimuli (UPS and EPS).There was no correlation betweenthe two variables (rs = .04, P =.805). Regression lines are plotted forconvenience. n = 40, UPS, unexpected electrical pain; EPS, expected electrical pain; NRS, numerical rating scale.

5 Conclusions and implications

In conclusion, the aim of our study was to investigate a method for point-of-care pain monitoring in adults in real time. To our knowledge, cerebral oxygenation using a portable two-channel NIRS for bedside pain monitoring has never been investigated in alert adults under standardized, randomized and sham-controlled conditions. Due to experiments mainly in infants, the results were promising and led to our hypothesis expecting similar results in awake adults. Unfortunately, we could not prove the hypothesis that SctO2 monitored by a two-channel NIRS increases following painful stimuli in contrast to non-painful and sham stimuli and that it correlates with subjective pain perception as assessed by NRS in alert volunteers. Here, changes in SctO2 are most likely unspecific. Therefore, point-of-care pain assessment in awake humans remains still a challenge.

Highlights

  • Due to an increase of cerebral blood flow SctO2 changes might quantify pain.

  • In awake volunteers, frontal changes in SctO2 via NIRS are most likely unspecific for pain.

  • Point-of-care pain monitoring remains a challenge in adults.

DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2017.05.005.

☆ Preliminary data of this study were presented in parts as a poster at the annual meeting of the German Society of Anaesthesiology and Intensive Care Medicine ‘HAI 2013’, 19-21 September 2013, Berlin, Germany and as a lecture at ‘DAC 2016’, 14–16 April 2016, Leipzig, Germany.

  1. Ethical issues: Procedures were proposed to each participant and written informed consent in accordance to the Declaration of Helsinki was obtained. Institutional Review Board: Ethics Committee of the Faculty of Medicine of the Ruhr University Bochum, Germany Chairman: Prof. Dr. M. Zenz; Gesundheitscampus 33, 44801 Bochum, Germany; No. 4501-12; approval: 23 Oct 2012.

  2. Conflict of interest: CMF: received a sponsorship award for young pain scientists 2012 from Janssen-Cilag GmbH. Further, she received payments for clinical lectures from OrionPharma and Grünenthal Group 2013, all unrelated to the current study and relationships in the past. GJ: none known. EPZ: received consultancy fees from Mundipharma, MSD, Janssen-Cilag and Grünenthal. EPZ has a grant pending from Mundipharma. She has received payment for lectures from Mundipharma, Lilly, MSD, Pfizer and Grünenthal, and travel/accommodation/meetings expenses unrelated to other activities from Mundipharma. Funding was not related to the present research. PZ: none known.

  3. Funding: Costs of this study (e.g. expendable materials, proband fees) were obtained from institutional sources.

  4. Authors’ contributions: CMF: drafted ethical proposal and manuscript, performed statistics; GJ: collected data, did statistical analyses; EMPZ: responsible for concept, gave advice and made critical revisions; PKZ: responsible for concept, participated in drafting the manuscript.

References

[1] Ledowski T, Reimer M, Chavez V, Kapoor V, Wenk M. Effects of acute postoperative pain on catecholamine plasma levels, hemodynamic parameters, and cardiac autonomic control. Pain 2012;153:759–64.Suche in Google Scholar

[2] Barvais L, Engelman E, Eba JM, Coussaert E, Cantraine F, Kenny GN. Effect site concentrations of remifentanil and pupil response to noxious stimulation. Br J Anaesth 2003;91:347–52.Suche in Google Scholar

[3] Bonhomme V, Uutela K, Hans G, Maquoi I, Born JD, Brichant JF, Lamy M, Hans P. Comparison of the surgical Pleth IndexTM with haemodynamic variables to assess nociception-anti-nociception balance during general anaesthesia. Br J Anaesth 2011;106:101–11.Suche in Google Scholar

[4] Ledowski T, Ang B, Schmarbeck T, Rhodes J. Monitoring of sympathetic tone to assess postoperative pain: skin conductance vs surgical stress index. Anaesthesia 2009;64:727–31.Suche in Google Scholar

[5] Ledowski T, Bromilow J, Paech MJ, Storm H, Hacking R, Schug SA. Monitoring of skin conductance to assess postoperative pain intensity. Br J Anaesth 2006;97:862–5.Suche in Google Scholar

[6] Cowen R, Stasiowska MK, Laycock H, Bantel C. Assessing pain objectively: the use of physiological markers. Anaesthesia 2015;70:828–47.Suche in Google Scholar

[7] De Salvo S, Naro A, Bonanno L, Russo M, Muscarà N, Bramanti P, Marino S. Assessment of nociceptive system in vegetative and minimally conscious state by using laser evoked potentials. Brain Inj 2015;29:1467–74.Suche in Google Scholar

[8] Jess G, Pogatzki-Zahn EM, Zahn PK, Meyer-Frießem CH. Monitoring heart rate variability to assess experimentally induced pain using the analgesia nociception index: A randomised volunteer study. Eur J Anaesthesiol 2016;33:118–25.Suche in Google Scholar

[9] Roy CS, Sherrington CS. On the Regulation of the Blood-supply of the Brain. J Physiol 1890;11, 85-158.17.Suche in Google Scholar

[10] Villringer A, Planck J, Hock C, Schleinkofer L, Dirnagl U. Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults. Neurosci Lett 1993;154:101–4.Suche in Google Scholar

[11] Owen-Reece H, Smith M, Elwell CE, Goldstone JC. Near infrared spectroscopy. Br J Anaesth 1999;82:418–26.Suche in Google Scholar

[12] Highton D, Elwell C, Smith M. Noninvasive cerebral oximetry: is there light at the end of the tunnel? Curr Opin Anaesthesiol 2010;23:576–81.Suche in Google Scholar

[13] Goldman S, Sutter F, Ferdinand F, Trace C. Optimizing intraoperative cerebral oxygen delivery using noninvasive cerebral oximetry decreases the incidence of stroke for cardiac surgical patients. Heart Surg Forum 2004;7:E376–81.Suche in Google Scholar

[14] Murkin JM, Adams SJ, Novick RJ, Quantz M, Bainbridge D, Iglesias I, Cleland A, Schaefer B, Irwin B, Fox S. Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective study. Anesth Analg 2007;104:51–8.Suche in Google Scholar

[15] Bartocci M, Bergqvist LL, Lagercrantz H, Anand KJ. Pain activates cortical areas in the preterm newborn brain. Pain 2006;122:109–17.Suche in Google Scholar

[16] Slater R, Cantarella A, Franck L, Meek J, Fitzgerald M. How well do clinical pain assessment tools reflect pain in infants? PLoS Med 2008;5:e129.Suche in Google Scholar

[17] Slater R, Cantarella A, Gallella S, Worley A, Boyd S, Meek J, Fitzgerald M. Cortical pain responses in human infants. J Neurosci 2006;26:3662–6.Suche in Google Scholar

[18] Ranger M, Gélinas C. Innovating in pain assessment of the critically ill: exploring cerebral near-infrared spectroscopy as a bedside approach. Pain Manag Nurs Off J Am Soc Pain Manag Nurses 2014;15:519–29.Suche in Google Scholar

[19] Ranger M, Johnston CC, Anand KJS. Current controversies regarding pain assessment in neonates. Semin Perinatol 2007;31:283–8.Suche in Google Scholar

[20] Yücel MA, Aasted CM, Petkov MP, Borsook D, Boas DA, Becerra L. Specificity of hemodynamic brain responses to painful stimuli: a functional near-infrared spectroscopy study. Sci Rep 2015;5:9469.Suche in Google Scholar

[21] Gelinas C, Choiniere M, Ranger M, Denault A, Deschamps A, Johnston C. Toward a new approach for the detection of pain in adult patients undergoing cardiac surgery: near-infrared spectroscopy-a pilot study. Heart Lung 2010;39:485–93.Suche in Google Scholar

[22] Lee C-H, Sugiyama T, Kataoka A, Kudo A, Fujino F, Chen Y-W, Mitsuyama Y, Nomura S, Yoshioka T. Analysis for distinctive activation patterns of pain and itchy in the human brain cortex measured using near infrared spectroscopy (NIRS). PLoS ONE 2013;8:e75360.Suche in Google Scholar

[23] Ferrari M, Mottola L, Quaresima V. Principles, techniques, and limitations of near infrared spectroscopy. Can J Appl Physiol Rev Can Physiol Appliquée 2004;29:463–87.Suche in Google Scholar

[24] Madsen PL, Secher NH. Near-infrared oximetry of the brain. Prog Neurobiol 1999;58:541–60.Suche in Google Scholar

[25] Ito H, Kanno I, Fukuda H. Human cerebral circulation: positron emission tomography studies. Ann Nucl Med 2005;19:65–74.Suche in Google Scholar

[26] Ghosh A, Elwell C, Smith M. Review article: cerebral near-infrared spectroscopy in adults: a work in progress. Anesth Analg 2012;115:1373–83.Suche in Google Scholar

[27] Heringlake M, Garbers C, Käbler J-H, Anderson I, Heinze H, Schön J, Berger K-U, Dibbelt L, Sievers H-H, Hanke T. Preoperative cerebral oxygen saturation and clinical outcomes in cardiac surgery. Anesthesiology 2011;114:58–69.Suche in Google Scholar

[28] Fischer GW, Torrillo TM, Weiner MM, Rosenblatt MA. The use of cerebral oximetry as a monitor of the adequacy of cerebral perfusion in a patient undergoing shoulder surgery in the beach chair position. Pain Pract Off J World Inst Pain 2009;9:304–7.Suche in Google Scholar

[29] Murkin JM, Arango M. Near-infrared spectroscopy as an index of brain and tissue oxygenation. Br J Anaesth 2009;103(Suppl 1):i3–13.Suche in Google Scholar

[30] Zanatta P, Forti A. Effectiveness of NIRS to sample the frontal brain cortex in all cardiac surgery patients. Minerva Anestesiol 2011;77:1124–5.Suche in Google Scholar

[31] Viola S, Viola P, Litterio P, Buongarzone MP, Fiorelli L. Pathophysiology of migraine attack with prolonged aura revealed by transcranial Doppler and near infrared spectroscopy. Neurol Sci 2010;31(Suppl 1):S165–6.Suche in Google Scholar

[32] Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal. Nature 2001;412:150–7.Suche in Google Scholar

[33] Olsson E, Ahlsén G, Eriksson M. Skin-to-skin contact reduces near-infrared spectroscopy pain responses in premature infants during blood sampling. Acta Paediatr Oslo Nor 1992 2016;105:376–80.Suche in Google Scholar

[34] Apkarian AV. Pain perception in relation to emotional learning. Curr Opin Neurobiol 2008;18:464–8.Suche in Google Scholar

[35] Ranger M, Grunau RE. How do babies feel pain? eLife 2015;4:e07552.Suche in Google Scholar

[36] Morinaga K, Akiyoshi J, Matsushita H, Ichioka S, Tanaka Y, Tsuru J, Hanada H. Anticipatory anxiety-induced changes in human lateral prefrontal cortex activity. Biol Psychol 2007;74:34–8.Suche in Google Scholar

[37] Iannetti GD, Mouraux A. From the neuromatrix to the pain matrix (and back). Exp Brain Res 2010;205:1–12.Suche in Google Scholar

[38] Becerra L, Aasted CM, Boas DA, George E, Yücel MA, Kussman BD, Kelsey P, Borsook D. Brain measures of nociception using near-infrared spectroscopy in patients undergoing routine screening colonoscopy. Pain 2016;157: 840–8.Suche in Google Scholar

[39] Narsinghani U, Anand KJS. Developmental Neurobiology of Pain in Neonatal Rats. Lab Anim 2000;29:27–39.Suche in Google Scholar

[40] Bingel U, Wanigasekera V, Wiech K, Ni Mhuircheartaigh R, Lee MC, Ploner M, Tracey I. The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Sci Transl Med 2011;3: 70ra14.Suche in Google Scholar

[41] Wang G, Erpelding N, Davis KD. Sex differences in connectivity of the subgenual anterior cingulate cortex. Pain 2014;155:755–63.Suche in Google Scholar

[42] Valencia L, Rodríguez-Pérez A, Ojeda N, Santana RY, Morales L, Padrón O. Baseline cerebral oximetry values depend on non-modifiable patient characteristics. Anaesth Crit Care Pain Med 2015;34:345–8.Suche in Google Scholar

[43] Storm H, Støen R, Klepstad P, Skorpen F, Qvigstad E, Raeder J. Nociceptive stimuli responses at different levels of general anaesthesia and genetic variability. Acta Anaesthesiol Scand 2013;57:89–99.Suche in Google Scholar
Received: 2017-03-22
Revised: 2017-05-01
Accepted: 2017-05-02
Published Online: 2017-07-01
Published in Print: 2017-07-01

© 2017 Scandinavian Association for the Study of Pain

Artikel in diesem Heft

  2. Scandinavian Journal of Pain
  3. Editorial comment
  4. Glucocorticoids – Efficient analgesics against postherpetic neuralgia?
  5. Original experimental
  6. Effect of intrathecal glucocorticoids on the central glucocorticoid receptor in a rat nerve ligation model
  7. Editorial comment
  8. Important new insight in pain and pain treatment induced changes in functional connectivity between the Pain Matrix and the Salience, Central Executive, and Sensorimotor networks
  9. Original experimental
  10. Salience, central executive, and sensorimotor network functional connectivity alterations in failed back surgery syndrome
  11. Editorial comment
  12. Education and support strategies improve assessment and management of pain by nurses
  13. Clinical pain research
  14. Using education and support strategies to improve the way nurses assess regular and transient pain – A quality improvement study of three hospitals
  15. Editorial comment
  16. The interference of pain with task performance: Increasing ecological validity in research
  17. Original experimental
  18. The disruptive effects of pain on multitasking in a virtual errands task
  19. Editorial comment
  20. Analyzing transition from acute back pain to chronic pain with linear mixed models reveals a continuous chronification of acute back pain
  21. Observational study
  22. From acute to chronic back pain: Using linear mixed models to explore changes in pain intensity, disability, and depression
  23. Editorial comment
  24. NSAIDs relieve osteoarthritis (OA) pain, but cardiovascular safety in question even for diclofenac, ibuprofen, naproxen, and celecoxib: what are the alternatives?
  25. Clinical pain research
  26. Efficacy and safety of diclofenac in osteoarthritis: Results of a network meta-analysis of unpublished legacy studies
  27. Editorial comment
  28. Editorial comment on Nina Kreddig’s and Monika Hasenbring’s study on pain anxiety and fear of (re) injury in patients with chronic back pain: Sex as a moderator
  29. Clinical pain research
  30. Pain anxiety and fear of (re) injury in patients with chronic back pain: Sex as a moderator
  31. Editorial comment
  32. Intraoral QST – Mission impossible or not?
  33. Clinical pain research
  34. Multifactorial assessment of measurement errors affecting intraoral quantitative sensory testing reliability
  35. Editorial comment
  36. Objective measurement of subjective pain-experience: Real nociceptive stimuli versus pain expectation
  37. Clinical pain research
  38. Cerebral oxygenation for pain monitoring in adults is ineffective: A sequence-randomized, sham controlled study in volunteers
  39. Editorial comment
  40. Association between adolescent and parental use of analgesics
  41. Observational study
  42. The association between adolescent and parental use of non-prescription analgesics for headache and other somatic pain – A cross-sectional study
  43. Editorial comment
  44. Cancer-pain intractable to high-doses systemic opioids can be relieved by intraspinal local anaesthetic plus an opioid and an alfa2-adrenoceptor agonist
  45. Clinical pain research
  46. Spinal analgesia for severe cancer pain: A retrospective analysis of 60 patients
  47. Editorial comment
  48. Specific symptoms and signs of unstable back segments and curative surgery?
  49. Clinical pain research
  50. Symptoms and signs possibly indicating segmental, discogenic pain. A fusion study with 18 years of follow-up
  51. Editorial comment
  52. Local anaesthesia methods for analgesia after total hip replacement: Problems of anatomy, methodology and interpretation?
  53. Clinical pain research
  54. Local infiltration analgesia or femoral nerve block for postoperative pain management in patients undergoing total hip arthroplasty. A randomized, double-blind study
  55. Editorial
  56. Scientific presentations at the 2017 annual meeting of the Scandinavian Association for the Study of Pain (SASP)
  57. Abstracts
  58. Correlation between quality of pain and depression: A post-operative assessment of pain after caesarian section among women in Ghana
  59. Abstracts
  60. Dynamic and static mechanical pain sensitivity is associated in women with migraine
  61. Abstracts
  62. The number of active trigger points is associated with sensory and emotional aspects of health-related quality of life in tension type headache
  63. Abstracts
  64. Chronic neuropathic pain following oxaliplatin and docetaxel: A 5-year follow-up questionnaire study
  65. Abstracts
  66. Expression of α1 adrenergic receptor subtypes by afferent fibers that innervate rat masseter muscle
  67. Abstracts
  68. Buprenorphine alleviation of pain does not compromise the rat monoarthritic pain model
  69. Abstracts
  70. Association between pain, disability, widespread pressure pain hypersensitivity and trigger points in subjects with neck pain
  71. Abstracts
  72. Association between widespread pressure pain hypersensitivity, health history, and trigger points in subjects with neck pain
  73. Abstracts
  74. Neuromas in patients with peripheral nerve injury and amputation - An ongoing study
  75. Abstracts
  76. The link between chronic musculoskeletal pain and sperm quality in overweight orthopedic patients
  77. Abstracts
  78. Several days of muscle hyperalgesia facilitates cortical somatosensory excitability
  79. Abstracts
  80. Social stress, epigenetic changes and pain
  81. Abstracts
  82. Characterization of released exosomes from satellite glial cells under normal and inflammatory conditions
  83. Abstracts
  84. Cell-based platform for studying trigeminal satellite glial cells under normal and inflammatory conditions
  85. Abstracts
  86. Tramadol in postoperative pain – 1 mg/ml IV gave no pain reduction but more side effects in third molar surgery
  87. Abstracts
  88. Tempo-spatial discrimination to non-noxious stimuli is better than for noxious stimuli
  89. Abstracts
  90. The encoding of the thermal grill illusion in the human spinal cord
  91. Abstracts
  92. Effect of cocoa on endorphin levels and craniofacial muscle sensitivity in healthy individuals
  93. Abstracts
  94. The impact of naloxegol treatment on gastrointestinal transit and colonic volume
  95. Abstracts
  96. Preoperative downregulation of long-noncoding RNA Meg3 in serum of patients with chronic postoperative pain after total knee replacement
  97. Abstracts
  98. Painful diabetic polyneuropathy and quality of life in Danish type 2 diabetic patients
  99. Abstracts
  100. “What about me?”: A qualitative explorative study on perspectives of spouses living with complex chronic pain patients
  101. Abstracts
  102. Increased postural stiffness in patients with knee osteoarthritis who are highly sensitized
  103. Abstracts
  104. Efficacy of dry needling on latent myofascial trigger points in male subjects with neck/shoulders musculoskeletal pain. A case series
  105. Abstracts
  106. Identification of pre-operative of risk factors associated with persistent post-operative pain by self-reporting tools in lower limb amputee patients – A feasibility study
  107. Abstracts
  108. Renal function estimations and dose recommendations for Gabapentin, Ibuprofen and Morphine in acute hip fracture patients
  109. Abstracts
  110. Evaluating the ability of non-rectangular electrical pulse forms to preferentially activate nociceptive fibers by comparing perception thresholds
  111. Abstracts
  112. Detection of systemic inflammation in severely impaired chronic pain patients, and effects of a CBT-ACT-based multi-modal pain rehabilitation program
  113. Abstracts
  114. Fixed or adapted conditioning intensity for repeated conditioned pain modulation
  115. Abstracts
  116. Combined treatment (Norspan, Gabapentin and Oxynorm) was found superior in pain management after total knee arthroplasty
  117. Abstracts
  118. Effects of conditioned pain modulation on the withdrawal pattern to nociceptive stimulation in humans – Preliminary results
  119. Abstracts
  120. Application of miR-223 onto the dorsal nerve roots in rats induces hypoexcitability in the pain pathways
  121. Abstracts
  122. Acute muscle pain alters corticomotor output of the affected muscle stronger than a synergistic, ipsilateral muscle
  123. Abstracts
  124. The subjective sensation induced by various thermal pulse stimulation in healthy volunteers
  125. Abstracts
  126. Assessing Offset Analgesia through electrical stimulations in healthy volunteers
  127. Abstracts
  128. Metastatic lung cancer in patient with non-malignant neck pain: A case report
  129. Abstracts
  130. The size of pain referral patterns from a tonic painful mechanical stimulus is increased in women
  131. Abstracts
  132. Oxycodone and macrogol 3350 treatment reduces anal sphincter relaxation compared to combined oxycodone and naloxone tablets
  133. Abstracts
  134. The effect of UVB-induced skin inflammation on histaminergic and non-histaminergic evoked itch and pain
  135. Abstracts
  136. Topical allyl-isothiocyanate (mustard oil) as a TRPA1-dependent human surrogate model of pain, hyperalgesia, and neurogenic inflammation – A dose response study
  137. Abstracts
  138. Dissatisfaction and persistent post-operative pain following total knee replacement – A 5 year follow-up of all patients from a whole region
  139. Abstracts
  140. Paradoxical differences in pain ratings of the same stimulus intensity
  141. Abstracts
  142. Pain assessment and post-operative pain management in orthopedic patients
  143. Abstracts
  144. Combined electric and pressure cuff pain stimuli for assessing conditioning pain modulation (CPM)
  145. Abstracts
  146. The effect of facilitated temporal summation of pain, widespread pressure hyperalgesia and pain intensity in patients with knee osteoarthritis on the responds to Non-Steroidal Anti-Inflammatory Drugs – A preliminary analysis
  147. Abstracts
  148. How to obtain the biopsychosocial record in multidisciplinary pain clinic? An action research study
  149. Abstracts
  150. Experimental neck muscle pain increase pressure pain threshold over cervical facet joints
  151. Abstracts
  152. Are we using Placebo effects in specialized Palliative Care?
  153. Abstracts
  154. Prevalence and pattern of helmet-induced headache among Danish military personnel
  155. Abstracts
  156. Aquaporin 4 expression on trigeminal satellite glial cells under normal and inflammatory conditions
  157. Abstracts
  158. Preoperative synovitis in knee osteoarthritis is predictive for pain 1 year after total knee arthroplasty
  159. Abstracts
  160. Biomarkers alterations in trapezius muscle after an acute tissue trauma: A human microdialysis study
  161. Abstracts
  162. PainData: A clinical pain registry in Denmark
  163. Abstracts
  164. A novel method for investigating the importance of visual feedback on somatosensation and bodily-self perception
  165. Abstracts
  166. Drugs that can cause respiratory depression with concomitant use of opioids
  167. Abstracts
  168. The potential use of a serious game to help patients learn about post-operative pain management – An evaluation study
  169. Abstracts
  170. Modelling activity-dependent changes of velocity in C-fibers
  171. Abstracts
  172. Choice of rat strain in pre-clinical pain-research – Does it make a difference for translation from animal model to human condition?
  173. Abstracts
  174. Omics as a potential tool to identify biomarkers and to clarify the mechanism of chronic pain development
  175. Abstracts
  176. Evaluation of the benefits from the introduction meeting for patients with chronic non-malignant pain and their relatives in interdisciplinary pain center
  177. Observational study
  178. The changing face of acute pain services
  179. Observational study
  180. Chronic pain in multiple sclerosis: A10-year longitudinal study
  181. Clinical pain research
  182. Functional disability and depression symptoms in a paediatric persistent pain sample
  183. Observational study
  184. Pain provocation following sagittal plane repeated movements in people with chronic low back pain: Associations with pain sensitivity and psychological profiles
  185. Observational study
  186. A longitudinal exploration of pain tolerance and participation in contact sports
  187. Original experimental
  188. Taking a break in response to pain. An experimental investigation of the effects of interruptions by pain on subsequent activity resumption
  189. Clinical pain research
  190. Sex moderates the effects of positive and negative affect on clinical pain in patients with knee osteoarthritis
  191. Original experimental
  192. The effects of a brief educational intervention on medical students’ knowledge, attitudes and beliefs towards low back pain
  193. Observational study
  194. The association between pain characteristics, pain catastrophizing and health care use – Baseline results from the SWEPAIN cohort
  195. Topical review
  196. Couples coping with chronic pain: How do intercouple interactions relate to pain coping?
  197. Narrative review
  198. The wit and wisdom of Wilbert (Bill) Fordyce (1923 - 2009)
  199. Letter to the Editor
  200. Unjustified extrapolation
  201. Letter to the Editor
  202. Response to: “Letter to the Editor entitled: Unjustified extrapolation” [by authors: Supp G., Rosedale R., Werneke M.]
https://doi.org/10.1016/j.sjpain.2017.05.001
Schlagwörter für diesen Artikel
Pain monitoring; Cerebral oxygen saturation; NIRS; Near infrared spectroscopy; SctO2

Artikel in diesem Heft

  2. Scandinavian Journal of Pain
  3. Editorial comment
  4. Glucocorticoids – Efficient analgesics against postherpetic neuralgia?
  5. Original experimental
  6. Effect of intrathecal glucocorticoids on the central glucocorticoid receptor in a rat nerve ligation model
  7. Editorial comment
  8. Important new insight in pain and pain treatment induced changes in functional connectivity between the Pain Matrix and the Salience, Central Executive, and Sensorimotor networks
  9. Original experimental
  10. Salience, central executive, and sensorimotor network functional connectivity alterations in failed back surgery syndrome
  11. Editorial comment
  12. Education and support strategies improve assessment and management of pain by nurses
  13. Clinical pain research
  14. Using education and support strategies to improve the way nurses assess regular and transient pain – A quality improvement study of three hospitals
  15. Editorial comment
  16. The interference of pain with task performance: Increasing ecological validity in research
  17. Original experimental
  18. The disruptive effects of pain on multitasking in a virtual errands task
  19. Editorial comment
  20. Analyzing transition from acute back pain to chronic pain with linear mixed models reveals a continuous chronification of acute back pain
  21. Observational study
  22. From acute to chronic back pain: Using linear mixed models to explore changes in pain intensity, disability, and depression
  23. Editorial comment
  24. NSAIDs relieve osteoarthritis (OA) pain, but cardiovascular safety in question even for diclofenac, ibuprofen, naproxen, and celecoxib: what are the alternatives?
  25. Clinical pain research
  26. Efficacy and safety of diclofenac in osteoarthritis: Results of a network meta-analysis of unpublished legacy studies
  27. Editorial comment
  28. Editorial comment on Nina Kreddig’s and Monika Hasenbring’s study on pain anxiety and fear of (re) injury in patients with chronic back pain: Sex as a moderator
  29. Clinical pain research
  30. Pain anxiety and fear of (re) injury in patients with chronic back pain: Sex as a moderator
  31. Editorial comment
  32. Intraoral QST – Mission impossible or not?
  33. Clinical pain research
  34. Multifactorial assessment of measurement errors affecting intraoral quantitative sensory testing reliability
  35. Editorial comment
  36. Objective measurement of subjective pain-experience: Real nociceptive stimuli versus pain expectation
  37. Clinical pain research
  38. Cerebral oxygenation for pain monitoring in adults is ineffective: A sequence-randomized, sham controlled study in volunteers
  39. Editorial comment
  40. Association between adolescent and parental use of analgesics
  41. Observational study
  42. The association between adolescent and parental use of non-prescription analgesics for headache and other somatic pain – A cross-sectional study
  43. Editorial comment
  44. Cancer-pain intractable to high-doses systemic opioids can be relieved by intraspinal local anaesthetic plus an opioid and an alfa2-adrenoceptor agonist
  45. Clinical pain research
  46. Spinal analgesia for severe cancer pain: A retrospective analysis of 60 patients
  47. Editorial comment
  48. Specific symptoms and signs of unstable back segments and curative surgery?
  49. Clinical pain research
  50. Symptoms and signs possibly indicating segmental, discogenic pain. A fusion study with 18 years of follow-up
  51. Editorial comment
  52. Local anaesthesia methods for analgesia after total hip replacement: Problems of anatomy, methodology and interpretation?
  53. Clinical pain research
  54. Local infiltration analgesia or femoral nerve block for postoperative pain management in patients undergoing total hip arthroplasty. A randomized, double-blind study
  55. Editorial
  56. Scientific presentations at the 2017 annual meeting of the Scandinavian Association for the Study of Pain (SASP)
  57. Abstracts
  58. Correlation between quality of pain and depression: A post-operative assessment of pain after caesarian section among women in Ghana
  59. Abstracts
  60. Dynamic and static mechanical pain sensitivity is associated in women with migraine
  61. Abstracts
  62. The number of active trigger points is associated with sensory and emotional aspects of health-related quality of life in tension type headache
  63. Abstracts
  64. Chronic neuropathic pain following oxaliplatin and docetaxel: A 5-year follow-up questionnaire study
  65. Abstracts
  66. Expression of α1 adrenergic receptor subtypes by afferent fibers that innervate rat masseter muscle
  67. Abstracts
  68. Buprenorphine alleviation of pain does not compromise the rat monoarthritic pain model
  69. Abstracts
  70. Association between pain, disability, widespread pressure pain hypersensitivity and trigger points in subjects with neck pain
  71. Abstracts
  72. Association between widespread pressure pain hypersensitivity, health history, and trigger points in subjects with neck pain
  73. Abstracts
  74. Neuromas in patients with peripheral nerve injury and amputation - An ongoing study
  75. Abstracts
  76. The link between chronic musculoskeletal pain and sperm quality in overweight orthopedic patients
  77. Abstracts
  78. Several days of muscle hyperalgesia facilitates cortical somatosensory excitability
  79. Abstracts
  80. Social stress, epigenetic changes and pain
  81. Abstracts
  82. Characterization of released exosomes from satellite glial cells under normal and inflammatory conditions
  83. Abstracts
  84. Cell-based platform for studying trigeminal satellite glial cells under normal and inflammatory conditions
  85. Abstracts
  86. Tramadol in postoperative pain – 1 mg/ml IV gave no pain reduction but more side effects in third molar surgery
  87. Abstracts
  88. Tempo-spatial discrimination to non-noxious stimuli is better than for noxious stimuli
  89. Abstracts
  90. The encoding of the thermal grill illusion in the human spinal cord
  91. Abstracts
  92. Effect of cocoa on endorphin levels and craniofacial muscle sensitivity in healthy individuals
  93. Abstracts
  94. The impact of naloxegol treatment on gastrointestinal transit and colonic volume
  95. Abstracts
  96. Preoperative downregulation of long-noncoding RNA Meg3 in serum of patients with chronic postoperative pain after total knee replacement
  97. Abstracts
  98. Painful diabetic polyneuropathy and quality of life in Danish type 2 diabetic patients
  99. Abstracts
  100. “What about me?”: A qualitative explorative study on perspectives of spouses living with complex chronic pain patients
  101. Abstracts
  102. Increased postural stiffness in patients with knee osteoarthritis who are highly sensitized
  103. Abstracts
  104. Efficacy of dry needling on latent myofascial trigger points in male subjects with neck/shoulders musculoskeletal pain. A case series
  105. Abstracts
  106. Identification of pre-operative of risk factors associated with persistent post-operative pain by self-reporting tools in lower limb amputee patients – A feasibility study
  107. Abstracts
  108. Renal function estimations and dose recommendations for Gabapentin, Ibuprofen and Morphine in acute hip fracture patients
  109. Abstracts
  110. Evaluating the ability of non-rectangular electrical pulse forms to preferentially activate nociceptive fibers by comparing perception thresholds
  111. Abstracts
  112. Detection of systemic inflammation in severely impaired chronic pain patients, and effects of a CBT-ACT-based multi-modal pain rehabilitation program
  113. Abstracts
  114. Fixed or adapted conditioning intensity for repeated conditioned pain modulation
  115. Abstracts
  116. Combined treatment (Norspan, Gabapentin and Oxynorm) was found superior in pain management after total knee arthroplasty
  117. Abstracts
  118. Effects of conditioned pain modulation on the withdrawal pattern to nociceptive stimulation in humans – Preliminary results
  119. Abstracts
  120. Application of miR-223 onto the dorsal nerve roots in rats induces hypoexcitability in the pain pathways
  121. Abstracts
  122. Acute muscle pain alters corticomotor output of the affected muscle stronger than a synergistic, ipsilateral muscle
  123. Abstracts
  124. The subjective sensation induced by various thermal pulse stimulation in healthy volunteers
  125. Abstracts
  126. Assessing Offset Analgesia through electrical stimulations in healthy volunteers
  127. Abstracts
  128. Metastatic lung cancer in patient with non-malignant neck pain: A case report
  129. Abstracts
  130. The size of pain referral patterns from a tonic painful mechanical stimulus is increased in women
  131. Abstracts
  132. Oxycodone and macrogol 3350 treatment reduces anal sphincter relaxation compared to combined oxycodone and naloxone tablets
  133. Abstracts
  134. The effect of UVB-induced skin inflammation on histaminergic and non-histaminergic evoked itch and pain
  135. Abstracts
  136. Topical allyl-isothiocyanate (mustard oil) as a TRPA1-dependent human surrogate model of pain, hyperalgesia, and neurogenic inflammation – A dose response study
  137. Abstracts
  138. Dissatisfaction and persistent post-operative pain following total knee replacement – A 5 year follow-up of all patients from a whole region
  139. Abstracts
  140. Paradoxical differences in pain ratings of the same stimulus intensity
  141. Abstracts
  142. Pain assessment and post-operative pain management in orthopedic patients
  143. Abstracts
  144. Combined electric and pressure cuff pain stimuli for assessing conditioning pain modulation (CPM)
  145. Abstracts
  146. The effect of facilitated temporal summation of pain, widespread pressure hyperalgesia and pain intensity in patients with knee osteoarthritis on the responds to Non-Steroidal Anti-Inflammatory Drugs – A preliminary analysis
  147. Abstracts
  148. How to obtain the biopsychosocial record in multidisciplinary pain clinic? An action research study
  149. Abstracts
  150. Experimental neck muscle pain increase pressure pain threshold over cervical facet joints
  151. Abstracts
  152. Are we using Placebo effects in specialized Palliative Care?
  153. Abstracts
  154. Prevalence and pattern of helmet-induced headache among Danish military personnel
  155. Abstracts
  156. Aquaporin 4 expression on trigeminal satellite glial cells under normal and inflammatory conditions
  157. Abstracts
  158. Preoperative synovitis in knee osteoarthritis is predictive for pain 1 year after total knee arthroplasty
  159. Abstracts
  160. Biomarkers alterations in trapezius muscle after an acute tissue trauma: A human microdialysis study
  161. Abstracts
  162. PainData: A clinical pain registry in Denmark
  163. Abstracts
  164. A novel method for investigating the importance of visual feedback on somatosensation and bodily-self perception
  165. Abstracts
  166. Drugs that can cause respiratory depression with concomitant use of opioids
  167. Abstracts
  168. The potential use of a serious game to help patients learn about post-operative pain management – An evaluation study
  169. Abstracts
  170. Modelling activity-dependent changes of velocity in C-fibers
  171. Abstracts
  172. Choice of rat strain in pre-clinical pain-research – Does it make a difference for translation from animal model to human condition?
  173. Abstracts
  174. Omics as a potential tool to identify biomarkers and to clarify the mechanism of chronic pain development
  175. Abstracts
  176. Evaluation of the benefits from the introduction meeting for patients with chronic non-malignant pain and their relatives in interdisciplinary pain center
  177. Observational study
  178. The changing face of acute pain services
  179. Observational study
  180. Chronic pain in multiple sclerosis: A10-year longitudinal study
  181. Clinical pain research
  182. Functional disability and depression symptoms in a paediatric persistent pain sample
  183. Observational study
  184. Pain provocation following sagittal plane repeated movements in people with chronic low back pain: Associations with pain sensitivity and psychological profiles
  185. Observational study
  186. A longitudinal exploration of pain tolerance and participation in contact sports
  187. Original experimental
  188. Taking a break in response to pain. An experimental investigation of the effects of interruptions by pain on subsequent activity resumption
  189. Clinical pain research
  190. Sex moderates the effects of positive and negative affect on clinical pain in patients with knee osteoarthritis
  191. Original experimental
  192. The effects of a brief educational intervention on medical students’ knowledge, attitudes and beliefs towards low back pain
  193. Observational study
  194. The association between pain characteristics, pain catastrophizing and health care use – Baseline results from the SWEPAIN cohort
  195. Topical review
  196. Couples coping with chronic pain: How do intercouple interactions relate to pain coping?
  197. Narrative review
  198. The wit and wisdom of Wilbert (Bill) Fordyce (1923 - 2009)
  199. Letter to the Editor
  200. Unjustified extrapolation
  201. Letter to the Editor
  202. Response to: “Letter to the Editor entitled: Unjustified extrapolation” [by authors: Supp G., Rosedale R., Werneke M.]
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 8.9.2025 von https://www.degruyterbrill.com/document/doi/10.1016/j.sjpain.2017.05.001/html
Button zum nach oben scrollen