Thomas Lundeberg

Lack of interchangeability between visual analogue and verbal rating pain scales: a cross sectional description of pain etiology groups

Background:Rating scales like the visual analogue scale, VAS, and the verbal rating scale, VRS, are often used for pain assessments both in clinical work and in research, despite the lack of a gold standard. Interchangeability of recorded pain intensity captured in the two scales has been discussed earlier, but not in conjunction with taking the influence of pain etiology into consideration.Methods:In this cross-sectional study, patients with their pain classified according to its etiology (chronic/idiopathic, nociceptive and neuropathic pain) were consecutively recruited for self-assessment of their actual pain intensity using a continuous VAS, 0–100, and a discrete five-category VRS. The data were analyzed with a non-parametric statistical method, suitable for comparison of scales with different numbers of response alternatives.Results:An overlapping of the VAS records relative the VRS categories was seen in all pain groups. Cut-off positions for the VAS records related to the VRS categories were found lower in patients with nociceptive pain relative patients suffering from chronic/idiopathic and neuropathic pain. When comparing the VAS records transformed into an equidistant five-category scale with the VRS records, systematic disagreements between the scales was shown in all groups. Furthermore, in the test-retest a low percentage of the patients agreed to the same pain level on the VAS while the opposite hold for the VRS.Conclusion:The pain intensity assessments on VAS and VRS are in this study, not interchangeable due to overlap of pain records between the two scales, systematic disagreements when comparing the two scales and a low percentage intra-scale agreement. Furthermore, the lower VAS cut-off positions relative the VRS labels indicate different meaning of the rated pain intensity depending on pain etiology. It is also indicated that the scales have non-linear properties and that the two scales probably have different interpretation. Our findings are in favor of using the VRS in pain intensity assessments but if still the VAS is preferred, the VAS data should be analyzed as continuous using statistical methods suitable for ordinal data. Furthermore, our findings indicate a risk to over or under estimate the patients perceived pain when interpreting condensed VAS data.

Quality of sleep in individuals with spinal cord injury: a comparison between patients with and without pain.

Study design:A cross-sectional descriptive study of self-reported quality of sleep in individuals with a spinal cord injury (SCI).Objectives:To assess and describe subjective quality of sleep in patients with SCI, with and without pain.Setting:Spinalis SCI unit, Stockholm, Sweden.Methods:A total of 230 patients with an SCI were mailed a questionnaire containing queries about pain intensities, pain unpleasantness, mood, and sleep quality (Basic Nordic Sleep Questionnaire) to assess quality of sleep in patients with SCI with and without pain.Results:Of the 192 questionnaires that were returned (response rate 83.4%), 191 were analysed. Patients were divided into three groups: (1) those who reported no pain (n=50), (2) those who reported intermittent pain (n=42), and (3) those who suffered from continuous pain (n=99). Patients suffering from continuous pain rated pain intensity and unpleasantness significantly higher than those who only suffered from intermittent pain. The group with continuous pain also reported the poorest quality of sleep and the highest ratings of anxiety and depression of the three groups. Anxiety, together with pain intensity and depression, were the main predictors for poor sleep quality.Conclusions:Poor subjective sleep quality was associated with higher ratings of pain intensity, anxiety, and depression. It is possible that melatonin serves as a modulator of these different aspects.Sponsorship:This study was made possible by grants from Spinalis Foundation.

Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine

The functional status of cells is under the control of external stimuli affecting the function of critical proteins and eventually gene expression. Signal sensing and transduction by messengers to specific effectors operate by post-translational modification of proteins, among which thiol redox switches play a fundamental role that is just beginning to be understood. The maintenance of the redox status is, indeed, crucial for cellular homeostasis and its dysregulation towards a more oxidized intracellular environment is associated with aberrant proliferation, ultimately related to diseases such as cancer, cardiovascular disease, and diabetes. Redox transitions occur in sensitive cysteine residues of regulatory proteins relevant to signaling, their evolution to metastable disulfides accounting for the functional redox switch. N-acetylcysteine (NAC) is a thiol-containing compound that is able to interfere with redox transitions of thiols and, thus, in principle, able to modulate redox signaling. We here review the redox chemistry of NAC, then screen possible mechanisms to explain the effects observed in NAC-treated normal and cancer cells; such effects involve a modification of global gene expression, thus of functions and morphology, with a leitmotif of a switch from proliferation to terminal differentiation. The regulation of thiol redox transitions in cell signaling is, therefore, proposed as a new tool, holding promise not only for a deeper explanation of mechanisms, but indeed for innovative pharmacological interventions.

Pain in a Swedish spinal cord injury population

Objective: To describe pain and associated variables in a prevalence group of persons with a sustained spinal cord injury (SCI) in the Swedish capital and its surroundings. Setting: Spinalis SCI Unit (outpatient clinic), Stockholm, Sweden. Design: Assessment over a 12-month period in a yearly health control. Subjects: Four hundred and fifty-six SCI patients. Results: Two hundred and ninety-one out of 456 SCI patients (63.7%) suffered from pain, and in 45.7% of these it was classified as being neurogenic. Aching pain was the most used descriptor (38.5%). The onset of pain was commonly within three months (73.5%). In 70.4% of patients pain occurred below the level of the lesion. Most patients identified pain as coming from one (55.0%) or two (28.2%) body regions. Rating of the general pain intensity on a visual analogue scale (VAS) was 46 out of 100 and rating of the worst pain intensity was 78 out of 100. Ninety-four out of 276 patients (32.3%) considered that their quality of life was significantly affected by pain. Conclusion: Pain was most common in patients with incomplete lesions (ASIA impairment grade D) and there was a correlation between pain and higher mean age at injury and between pain and female gender.

Comparison of symptoms and clinical findings in subgroups of individuals with patellofemoral pain

Patellofemoral pain syndrome (PFPS) is one of the most common musculoskeletal disorders. However, no consensus on the definition, classification, assessment, diagnosis, or management has been reached. We evaluated symptoms and clinical findings in subgroups of individuals with PFPS, classified on the basis of the findings in radiological examinations and compared the findings with knee-healthy subjects. An orthopedic surgeon and a physical therapist consecutively examined 80 patients clinically diagnosed as having PFPS and referred for physical therapy. The examination consisted of taking a case history and clinical tests. Radiography revealed pathology in 15 patients, and scintigraphic examination revealed focal uptake in 2 patients indicating pathology (group C). Diffusely increased uptake was present in 29 patients (group B). In the remaining 29 patients radiographic and scintigraphic examinations were normal (group A). Knee-healthy controls (group D) reported no clinical symptoms. No symptom could be statistically demonstrated to differ between the three patient groups. Knee-healthy subjects differed significantly from the three patient groups in all clinical tests measuring pain in response to the provocations; compression test, medial and lateral tenderness, passive gliding of the patella, but they also differed in Q angle. Differences in clinical tests between the patient groups were nonsignificant. The main finding in our study on patients clinically diagnosed with PFPS is that possible pathologies cannot be detected from the patients history or from commonly used clinical tests.

Gender related differences in pain in spinal cord injured individuals.

Study design: Out of a population of 456 patients with spinal cord injuries (SCI), 130 having pain were selected after matching, based on gender, age, American Spinal Injury Association (ASIA) impairment grade and level of lesion.Objective: To investigate whether gender differences with regard to pain perception and prevalence exist in a population of patients following spinal cord injury.Setting: Spinalis SCI Unit (out-patient clinic), Stockholm, Sweden.Method: 130 patients suffering from pain were assessed over a 12-month period in a yearly health control.Results: SCI women had a higher prevalence of nociceptive pain than men and their use of analgesics was greater. However, no differences between the sexes could be seen regarding pain and localization, onset, distribution, factors affecting pain, number of painful body regions, pain descriptors, ratings of pain intensities or in pain and life satisfaction.Conclusion: This study showed that SCI men and women describe their pain very similarly. However, SCI women had a higher prevalence of nociceptive pain than men and their use of opiates and non-steroid anti-inflammatory drugs (NSAIDs) was greater.

Differentiation of normal and cancer cells induced by sulfhydryl reduction : biochemical and molecular mechanisms

We examined the morphological, biochemical and molecular outcome of a nonspecific sulfhydryl reduction in cells, obtained by supplementation of N-acetyl-L-cysteine (NAC) in a 0.1–10u2009mM concentration range. In human normal primary keratinocytes and in colon and ovary carcinoma cells we obtained evidences for: (i) a dose-dependent inhibition of proliferation without toxicity or apoptosis; (ii) a transition from a proliferative mesenchymal morphology to cell-specific differentiated structures; (iii) a noticeable increase in cell–cell and cell–substratum junctions; (iv) a relocation of the oncogenic β-catenin at the cell–cell junctions; (v) inhibition of microtubules aggregation; (vi) upregulation of differentiation-related genes including p53, heat shock protein 27 gene, N-myc downstream-regulated gene 1, E-cadherin, and downregulation of cyclooxygenase-2; (vii) inhibition of c-Src tyrosine kinase. In conclusion, a thiol reduction devoid of toxicity as that operated by NAC apparently leads to terminal differentiation of normal and cancer cells through a pleiade of converging mechanisms, many of which are targets of the recently developed differentiation therapy.

Gender differences in electrical pain threshold responses to transcutaneous electrical nerve stimulation (TENS)

Gender differences in pain perception have been frequently discussed, but the documented gender-related pain-alleviating effects of non-pharmacological methods are sparse. In this study we aimed to investigate changes in electrical sensory thresholds and electrical pain thresholds, in response to high frequency transcutaneous electrical nerve stimulation, TENS, for 20 min in healthy women (n=29) and men (n=29). The thresholds were assessed pre-, during-, and post-TENS. The pattern of change in thresholds was evaluated with a rank-based statistical method regarding the level of systematic change, expressed as relative position (RP) and additional individual changes, expressed as relative rank variance (RV), with its 95% confidence intervals. Equal levels of systematic changes towards increased electrical sensory thresholds were seen in women and men post-TENS (RP, 0.35; 95% CI, 0.07, 0.63, and RP, 0.36; 95% CI, 0.17, 0.53, respectively). At the same point of time, systematic changes towards increased electrical pain thresholds were only seen in women (RP, 0.43; 95% CI, 0.27, 0.60), while they were unchanged in men (RP, -0.01; 95% CI, -0.13, 0.10). Significant additional individual variations were found in the womens responses of assessed electrical sensory and pain thresholds but not in the mens. It is concluded that both women and men responded with a significant increase of the electrical sensory threshold to high frequency TENS, but only women responded with increase of the electrical pain thresholds. The individual variation of the responses was greater in the women than in the men.

Global gene expression analysis in time series following N-acetyl L-cysteine induced epithelial differentiation of human normal and cancer cells in vitro.

BackgroundCancer prevention trials using different types of antioxidant supplements have been carried out at several occasions and one of the investigated compounds has been the antioxidant N-acetyl-L-cysteine (NAC). Studies at the cellular level have previously demonstrated that a single supplementation of NAC induces a ten-fold more rapid differentiation in normal primary human keratinocytes as well as a reversion of a colon carcinoma cell line from neoplastic proliferation to apical-basolateral differentiation [1]. The investigated cells showed an early change in the organization of the cytoskeleton, several newly established adherens junctions with E-cadherin/β-catenin complexes and increased focal adhesions, all features characterizing the differentiation process.MethodsIn order to investigate the molecular mechanisms underlying the proliferation arrest and accelerated differentiation induced by NAC treatment of NHEK and Caco-2 cells in vitro, we performed global gene expression analysis of NAC treated cells in a time series (1, 12 and 24 hours post NAC treatment) using the Affymetrix GeneChip™ Human Genome U95Av2 chip, which contains approximately 12,000 previously characterized sequences. The treated samples were compared to the corresponding untreated culture at the same time point.ResultsMicroarray data analysis revealed an increasing number of differentially expressed transcripts over time upon NAC treatment. The early response (1 hour) was transient, while a constitutive trend was commonly found among genes differentially regulated at later time points (12 and 24 hours). Connections to the induction of differentiation and inhibition of growth were identified for a majority of up- and down-regulated genes. All of the observed transcriptional changes, except for seven genes, were unique to either cell line. Only one gene, ID-1, was mutually regulated at 1 hour post treatment and might represent a common mediator of early NAC action.The detection of several genes that previously have been identified as stimulated or repressed during the differentiation of NHEK and Caco-2 provided validation of results. In addition, real-time kinetic PCR analysis of selected genes also verified the differential regulation as identified by the microarray platform.ConclusionNAC induces a limited and transient early response followed by a more consistent and extensively different expression at later time points in both the normal and cancer cell lines investigated. The responses are largely related to inhibition of proliferation and stimulation of differentiation in both cell types but are almost completely lineage specific. ID-1 is indicated as an early mediator of NAC action.

Evaluation of variations in sensory and pain threshold assessments by electrocutaneous stimulation

Assessed sensory and pain thresholds can change consequently to disturbances associated with ongoing pain. Such assessments could be an additional method in the daily clinical evaluation of perceived pain. To study the test–retest variability within-day and between-day of such procedures a newly developed instrument producing electrocutaneous stimulation, PainMatcher (PM), was used to assess the electrical sensory thresholds (EST) and pain thresholds (EPT) in healthy volunteers and in patients with pain. The produced data were considered ordinal and analyzed with rank-invariant statistics with properties of analyzing systematic disagreement, bias, and individual variations. The percentage agreements within ±1PM value for EST were in the two groups of healthy volunteers and patients in pain 94% and 92%, and for EPT assessments 49% and 78%, respectively. The variability in the EST assessments is possibly explained by a slight bias while the individual variations were negligible between the two occasions. The assessed EPT were unbiased in both groups while individual variations were significant among the healthy volunteers but negligible among the patients in pain. The EST was found to be increased in pain patients compared to healthy volunteers, p < 0.03, and the EPT decreased in pain patients compared to healthy volunteers, p < 0.001. The results in this study indicate stable and reliable assessments of EST and EPT except for a possible bias. The threshold assessment procedure followed in this study may be a valuable tool in the clinical evaluation of sensory and pain assessments in pain patients.