Standardized Quantitative Sensory Testing Protocol Research Articles

Quantitative sensory testing for assessment of somatosensory function in children and adolescents: a scoping review.

Quantitative sensory testing (QST) refers to a group of noninvasive psychophysical tests that examine responses to a range of calibrated mechanical and thermal stimuli. Quantitative sensory testing has been used extensively in adult pain research and has more recently been applied to pediatric pain research. The aims of this scoping review were to map the current state of the field, to identify gaps in the literature, and to inform directions for future research. Comprehensive searches were run in 5 databases. Titles, abstracts, and full texts were screened by 2 reviewers. Data related to the study aims were extracted and analyzed descriptively. A total of 16,894 unique studies were identified, of which 505 were screened for eligibility. After a full-text review, 301 studies were retained for analysis. Date of publication ranged from 1966 to 2023. However, the majority of studies (61%) were published within the last decade. Studies included participants across the developmental trajectory (ie, early childhood to adolescence) and most often included a combination of school-age children and adolescents (49%). Approximately 23% of studies were conducted in healthy samples. Most studies (71%) used only one QST modality. Only 14% of studies reported using a standardized QST protocol. Quantitative sensory testing in pediatric populations is an emerging and rapidly growing area of pain research. Future work is needed using comprehensive, standardized QST protocols to harness the full potential that this procedure can offer to our understanding of pediatric pain.

Neuropathic pain after surgery - A clinical validation study and assessment of accuracy measures of the 5-item NeuPPS scale.

The aim of this study was to validate the Neuropathic Pain for Post-Surgical Patients (NeuPPS) scale against clinically verified neuropathic pain (NP) by quantitative sensory testing (QST) as well as evaluation of other psychometric properties. The NeuPPS is a validated 5-item scale designed to evaluate NP in surgical populations. Data from 537 women aged >18 years scheduled for primary breast cancer surgery enrolled in a previous study for assessing risk factors for persistent pain after breast cancer treatment were used. Exclusion criteria were any other breast surgery or relevant comorbidity. A total of 448 eligible questionnaires were available at 6 months and 455 at 12 months. At 12 months, 290 patients completed a clinical examination and QST. NeuPPS and PainDETECT were analyzed against patients with and without clinically verified NP. NP was assessed using a standardized QST protocol including a clinical assessment. Furthermore, the NeuPPS and PainDETECT scores were psychometrically tested with an item response theory method, the Rasch analysis, to assess construct validity. Primary outcomes were the diagnostic accuracy measures for the NeuPPS, and secondary measures were psychometric analyses of the NeuPPS after 6 and 12 months. PainDETECT was also compared to clinically verified NP as well as NeuPPS comparing the stability of the estimates. Comparing the NeuPPS scores with verified NP using a receiver operating characteristic curve, the NeuPPS had an area under the curve of 0.80. Using a cutoff of 1, the NeuPPS had a sensitivity of 88% and a specificity of 59%, and using a cutoff of 3, the values were 35 and 96%, respectively. Analysis of the PainDETECT indicated that the used cutoffs may be inappropriate in a surgical population. The present study supports the validity of the NeuPPS as a screening tool for NP in a surgical population.

Dysmetabolism-related early sensory Deficits and their Relationship with peripheral Neuropathy Development.

To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development. 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. 196 were followed-up over a mean of 2.64 years for PN occurrence. Among those without T2DM, apart from male gender, height, higher fat and lower lean mass, only higher insulin resistance (IR, HOMA-R: OR 1.70, p=0.009, McAuley index OR: 0.62, p=0.008), was independently associated with EPSD. In T2DM, metabolic syndrome (MetS, OR 18.32, p<0.001) and skin advanced glycation end-products (AGEs, OR 5.66, p=0.003) were independent predictors of EPSD. In longitudinal analysis, T2DM (HR 3.32 vs. no DM, p<0.001), EPSD (aHR 1.88 vs. healthy, p=0.049 adjusted for DM and gender), higher IR and AGEs predicted PN development. Among the three EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (aHR 4.35, p=0.011). We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, MetS and higher AGEs which in turn are shown to influence PN development.

Continuum of sensory profiles in diabetes mellitus patients with and without neuropathy and pain.

Quantitative sensory testing (QST) assesses the functional integrity of small and large nerve fibre afferents and central somatosensory pathways; QST was assumed to provide insight into the mechanisms of neuropathy. We analysed QST profiles and phenotypes in patients with diabetes mellitus to study whether these could differentiate patients with and without pain and neuropathy. A standardized QST protocol was performed and 'loss and gain of function' abnormalities were analysed in four groups of subjects: diabetic patients with painful (pDSPN; n=220) and non-painful distal symmetric polyneuropathy (nDSPN; n=219), diabetic patients without neuropathy (DM; n=23) and healthy non-diabetic subjects (n=37). Based on the QST findings, diabetic subjects were further stratified into four predefined prototypic phenotypes: sensory loss (SL), thermal hyperalgesia (TH), mechanical hyperalgesia (MH) and healthy individuals. Patients in the pDSPN group showed the greatest hyposensitivity ('loss of function'), and DM patients showed the lowest, with statistically significant increases in thermal, thermal pain, mechanical and mechanical pain sensory thresholds. Accordingly, the frequency of the SL phenotype was significantly higher in the pDSPN subgroup (41.8%), than expected (p &lt; 0.0042). The proportion of 'gain of function' abnormalities was low in both pDSPN and nDSPN patients without significant differences. There is a continuum in the sensory profiles of diabetic patients, with a more pronounced sensory loss in pDSPN group probably reflecting somatosensory nerve fibre degeneration. An analysis of 'gain of function' abnormalities (allodynia, hyperalgesia) did not offer a key to understanding the pathophysiology of spontaneous diabetic peripheral neuropathic pain. This article, using quantitative sensory testing profiles in large cohorts of diabetic patients with and without polyneuropathy and pain, presents a continuum in the sensory profiles of diabetic patients, with more pronounced 'loss of function' abnormalities in painful polyneuropathy patients. Painful diabetic polyneuropathy probably represents a 'more progressed' type of neuropathy with more pronounced somatosensory nerve fibre degeneration. The proportion of 'gain of function' sensory abnormalities was low, and these offer limited understanding of pathophysiological mechanisms of spontaneous neuropathic pain.

Differences in Quantitative Sensory Testing Outcomes Between Patients With Low Back Pain in Primary Care and Pain-free Controls.

Quantitative Sensory Testing (QST) is used to test somatosensory functioning in on people with chronic LBP in secondary/tertiary health care facilities. Studies using QST-testing on LBP populations in primary care are scarce. Central Sensitization Inventory (CSI) measures central sensitization (CS)-related symptoms and studies investigating the differences between QST-testing and participants with LBP with a positive and negative score on the CSI questionnaire are also rare. This case-control study investigates differences of an extensive QST-measurement between patients with acute, chronic LBP, and pain-free controls (PFCs) in primary care. Secondary aim is to investigate differences of an extensive QST-measurement between "CS" and "no-CS" group. Participants with LBP were recruited from November 2016 to October 2019. Demographic and clinical information was collected and a standardized QST protocol was taken. Data analysis involved determining differences between groups. Data of 100 participants with LBP and 50 PFCs were analyzed. Heat pain thresholds, pressure pain threshold, and conditioned pain modulation local and remote were significantly moderately to relatively strongly affected by acute, chronic LBP and PFCs (P<0.001 to 0.001). Lumbar temporal summation was significantly moderately affected by acute, chronic LBP, and PFCs (P=0.001). Only pressure pain threshold showed significant difference between "CS" and "no-CS" group (P=0.001 to 0.002). Signs of enhanced nociceptive processing and disturbed top-down nociceptive modulation are apparent in people with acute and chronic LBP in primary care. Results indicate existence of central mechanisms in LBP in primary care.

Pain sensitivity in men who have never experienced a headache: an observer blinded case control study

BackgroundHeadache affects 90–99% of the population. Based on the question “Do you think that you never ever in your whole life have had a headache?” 4% of the population say that they have never experienced a headache. The rarity of never having had a headache suggests that distinct biological and environmental factors may be at play. We hypothesized that people who have never experienced a headache had a lower general pain sensitivity than controls.MethodsWe included 99 male participants, 47 headache free participants and 52 controls, in an observer blinded nested case-control study. We investigated cold pain threshold and heat pain threshold using a standardized quantitative sensory testing protocol, pericranial tenderness with total tenderness score and pain tolerance with the cold pressor test. Differences between the two groups were assessed with the unpaired Student’s t-test or Mann-Whitney U test as appropriate.ResultsThere was no difference in age, weight or mean arterial pressure between headache free participants and controls. We found no difference in pain detection threshold, pericranial tenderness or pain tolerance between headache free participants and controls.ConclusionOur study clearly shows that freedom from headache is not caused by a lower general pain sensitivity. The results support the hypothesis that headache is caused by specific mechanisms, which are present in the primary headache disorders, rather than by a decreased general sensitivity to painful stimuli.Trial registrationRegistered at ClinicalTrials.gov (NCT04217616), 3rd January 2020, retrospectively registered.

Assessment of Somatosensory Function and Self-harm in Adolescents

Self-harm is a risk factor for suicide in adolescents, with the prevalence highest in young people in group and residential care programs. Although no established risk factors for self-harm exist, adolescents who self-harm may have decreased pain sensitivity, but this has not been systematically investigated. To assess somatosensory function using quantitative sensory testing (QST) in children and adolescents living in care grouped by the number of episodes of self-harm in the past year and compare their somatosensory profiles with community control participants to investigate associations with the incidence or frequency of self-harm. Recruitment for this cross-sectional study began January 2019 and ended March 2020. Exclusion criteria included intellectual disability (intelligence quotient <70), autism spectrum disorder, or recent serious injury. Children and adolescents aged 12 to 17 years with no underlying health conditions were recruited from local authority residential care settings in Glasgow, UK, and schools and youth groups in London and Glasgow, UK. The volunteer sample of 64 participants included adolescents ages 13 to 17 years (34 [53%] females; 50 [78%] living in residential care; mean [SD] age, 16.34 [1.01] years) with varying incidents of self-harm in the past year (no episodes, 31 [48%]; 1-4 episodes, 12 [19%]; and ≥5 episodes, 2 [33%]). Participants were tested using a standardized QST protocol to establish baseline somatosensory function. Associations between somatosensory sensitivity, incidence and frequency of self-harm, residential status, age, gender, and prescription medication were calculated. Secondary outcomes assessed whether self-harm was associated with specific types of tests (ie, painful or nonpainful). A total of 64 participants ages 13 to 17 years completed testing (mean [SD] age, 16.3 [1.0] years; 34 [53%.] females and 30 [47%] males; 50 [78%] living in group homes). Adolescents with 5 or more self-harm incidences showed significant pain hyposensitivity compared with community control participants after adjusting for age, gender, and prescription drug use (SH group with 5 or more episodes vs control: -1.03 [95% CI, -1.47 to -0.60]; P < .001). Hyposensitivity also extended to nonpainful stimuli, similarly adjusted (SH group with 5 or more episodes vs control: -1.73; 95% CI, -2.62 to -0.84; P < .001). Pressure pain threshold accounted for most of the observed variance (31.1% [95% CI, 10.5% to 44.7%]; P < .001). The findings of this study suggest that sensory hyposensitivity is a phenotype of Adolescents who self-harm and that pressure pain threshold has clinical potential as a quick, inexpensive, and easily interpreted test to identify adolescents at increased risk of repeated self-harm.

74 Pain Modulatory Phenotypes Differentiate Chronic Pancreatitis Patients With Distinct Clinical Pain Profiles

INTRODUCTION: Pain is a common problem in patients with chronic pancreatitis (CP) and effective therapy remains a considerable challenge. Methods based on quantitative sensory testing (QST) provide information on pain modulation and have demonstrated promise in predicting future pain status and the efficacy of analgesics. The aims of this study were to evaluate the existence of CP subgroups with different pain modulatory phenotypes and to investigate associations with patients' clinical pain and psychological profiles. METHODS: This was a cross-sectional, multicentre study of CP outpatients. Patients fulfilled a number of questionaries' including the Brief Pain Inventory short form, the Hospital Anxiety and Depression Score as well as measures of Conditional and Situational Pain Catastrophising. Using a standardized QST protocol, we recorded pain detection thresholds (PDTs) to static muscle pressure stimulations at the “pancreatic dermatomes” on the upper abdomen and back and at three control areas. The ratio between pancreatic and control PDTs were calculated (PDT-index) to offset interindividual differences in absolute thresholds. The PDT-index was used in conjunction with repetitive pinprick stimulations (temporal summation) applied at the abdominal pancreatic dermatome to obtain a measure of segmental hyperalgesia. A conditioned pain modulation (CPM) paradigm was performed to investigate descending pain modulation. Patients were grouped based on normative QST reference values and questionnaire scores were compared across subgroups to investigate associations between patients' pain modulatory phenotypes and clinical pain and psychological profiles. RESULTS: A total of 91 patients were enrolled in the study. The mean age was 53.1 ± 12.7 y, 62% were men, and 65% had toxic etiology. Three distinct pain modulatory phenotypes were found: group 1 (n = 31) had normal pain modulation; group 2 (n = 17) had segmental sensitization; group 3 (n = 43) had widespread sensitization. Patients with widespread sensitization had higher pain score (P &lt; 0.01) and lower QOL (P &lt; 0.05) in comparison to segmental and normal. In contrast, psychological features were comparable across subgroups. CONCLUSION: CP patients with widespread sensitization have significantly higher levels of pain and lower QOL. QST characterizes the sensory profiles independently of the patient's psychological status and provides an unbiased proxy of pain processing. This information can be used for prognostication and tailoring of management strategies.

Relations between a standardized experimental stressor and cutaneous sensory function in patients with chronic pruritus and healthy controls: an experimental case-control study.

BackgroundWhile chronic pruritus (CP) is a frequent symptom, many aspects of its underlying pathophysiological mechanisms still need elucidation. Research on sensory cutaneous function and on the influence of stress has been conducted mainly in patients with atopic dermatitis but is lacking for patients with CP.ObjectiveTo assess whether a standardized social stressor influences cutaneous sensory function in patients with CP in comparison with healthy controls (HC).MethodsCase–control study; 33 CP and 30 HC were submitted to the standardized quantitative sensory testing protocol before and after the Trier Social Stress Test and 1 h later. Intraepidermal nerve fibre density (IENFD) was determined.ResultsMechanical pain sensitivity and mechanical detection thresholds were significantly higher in CP than in HC, and mechanical detection thresholds increased more in CP than in HC over the three measurements. In both groups, cold pain threshold increased and heat pain threshold decreased from before to after the stress test and remained constant 1 h later. Only in CP, almost all QST tests induced at least a small amount of pruritus, which was not significantly altered by the stress test. IENFD in pruritic skin was significantly reduced in CP when compared to healthy controls.ConclusionPeripheral thermal sensory function was not altered in CP despite reduced IENFD in lesional skin, but we could demonstrate central sensitization processes specifically in CP and influences of an acute stressor inducing more sensitivity to thermal pain in both groups.

How stable are quantitative sensory testing measurements over time? Report on 10-week reliability and agreement of results in healthy volunteers.

BackgroundQuantitative sensory testing (QST) is a diagnostic tool for the assessment of the somatosensory system. To establish QST as an outcome measure for clinical trials, the question of how similar the measurements are over time is crucial. Therefore, long-term reliability and limits of agreement of the standardized QST protocol of the German Research Network on Neuropathic Pain were tested.MethodsQST on the lower back and hand dorsum (dominant hand) were assessed twice in 22 healthy volunteers (10 males and 12 females; mean age: 46.6±13.0 years), with sessions separated by 10.0±2.9 weeks. All measurements were performed by one investigator. To investigate long-term reliability and agreement of QST, differences between the two measurements, correlation coefficients, intraclass correlation coefficients (ICCs), Bland–Altman plots (limits of agreement), and standard error of measurement were used.ResultsMost parameters of the QST were reliable over 10 weeks in healthy volunteers: Almost-perfect ICCs were observed for heat pain threshold (hand) and mechanical pain sensitivity (back). Substantial ICCs were observed for heat pain threshold (back), pressure pain threshold (back), mechanical pain sensitivity (hand), and vibration detection threshold (back and hand). Some QST parameters, such as cold detection threshold, exhibited low ICCs, but also very low variability. Generally, QST measures exhibited narrow limits of agreement in the Bland–Altman plots.ConclusionThe standardized QST protocol of the German Research Network on Neuropathic Pain is feasible to be used in treatment trials. Moreover, defining a statistically meaningful change is possible, which is a prerequisite for the use of QST in clinical trials as well as in long-term investigations of disease progression.

Altered pressure pain thresholds and increased wind-up in adult patients with chronic back pain with a history of childhood maltreatment: a quantitative sensory testing study.

Childhood maltreatment (CM) has been associated with an increased risk of nonspecific chronic low back pain (nsCLBP). However, the mechanisms underlying this association are unclear. Therefore, this study considered whether distinct types of CM are accompanied by specific alterations in somatosensory function. A total of 176 subjects with nsCLBP and 27 pain-free controls (PCs) were included. The Childhood Trauma Questionnaire (CTQ) was used to categorize patients into 2 groups (abused/neglected vs nonabused/nonneglected) for 5 types of CM (emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect). The standardized quantitative sensory testing protocol of the "German Research Network on Neuropathic Pain" was performed to obtain comprehensive profiles on somatosensory function, including detection and pain thresholds, pain sensitivity, and assessments of temporal summation (wind-up). Between 17.7% and 51.4% of subjects with nsCLBP reported CM, depending on the type of CM. Childhood Trauma Questionnaire subscores for emotional and sexual abuse were significantly higher in subjects with nsCLBP than in PCs. Compared with PCs, subjects with CM showed reduced pressure pain thresholds (PPTs), irrespective of the type of CM. Regarding distinct types of CM, subjects with nsCLBP with emotional abuse reported significantly higher wind-up than those without, and sexual abuse was accompanied by enhanced touch sensitivity. Our findings suggest that CM is nonspecifically associated with a decreased PPT in nsCLBP. Emotional abuse apparently leads to enhanced spinal pain summation, and sexual abuse leads to enhanced touch sensitivity. These results emphasize the importance of emotional abuse in nsCLBP and suggest that CM can induce long-term changes in adult somatosensory function.

Quantitative sensory testing in classical trigeminal neuralgia-a blinded study in patients with and without concomitant persistent pain.

The diagnostic criteria of the third International Classification of Headache Disorders state that there should be no neurological deficits in patients with classical trigeminal neuralgia (TN) at clinical examination. However, studies demonstrating sensory abnormalities at bedside examination in TN patients have questioned this. Our aim was to examine whether TN patients without sensory abnormalities at neurological examination have sensory abnormalities at quantitative sensory testing (QST) and whether there were any QST differences between TN with and without concomitant persistent pain. Thirty-six TN patients were investigated with the standardized QST protocol by the German Research Network on Neuropathic Pain. The investigators were blinded to presence of concomitant persistent pain and symptomatic side. Based on comparison to the German Research Network on Neuropathic Pain controls, z scores were calculated to process frequency analyses and Z-profiles. We found increased mechanical detection threshold on the symptomatic side (47.2% vs 0%, P = 0.008), asymptomatic side (33.3% vs 0%, P = 0.011), and hand (36% vs 0%, P < 0.001) in TN compared with controls. The Z-profiles demonstrated increased mechanical detection threshold on the symptomatic side compared with the asymptomatic side (-2.980 vs -2.166, P = 0.040). Thermal and mechanical hyperalgesia was detected bilaterally in the face and the hand. Trigeminal neuralgia patients with concomitant persistent pain tended to have higher mean z score values compared to TN with purely paroxysmal pain indicative of decreased detection thresholds. Trigeminal neuralgia patients with no sensory abnormalities at neurological examination had generalized subclinical hypoesthesia, which was more pronounced on the symptomatic side, and thermal and mechanical hyperalgesia. This could indicate pain-induced hypoesthesia and sensitization induced by central mechanisms.

Test-retest agreement and reliability of quantitative sensory testing 1 year after breast cancer surgery.

Quantitative sensory testing (QST) is used to assess sensory dysfunction and nerve damage by examining psychophysical responses to controlled, graded stimuli such as mechanical and thermal detection and pain thresholds. In the breast cancer population, 4 studies have used QST to examine persistent pain after breast cancer treatment, suggesting neuropathic pain being a prominent pain mechanism. However, the agreement and reliability of QST has not been described in the postsurgical breast cancer population, hindering exact interpretation of QST studies in this population. The aim of the present study was to assess test-retest properties of QST after breast cancer surgery. A total of 32 patients recruited from a larger ongoing prospective trial were examined with QST 12 months after breast cancer surgery and reexamined a week later. A standardized QST protocol was used, including sensory mapping for mechanical, warmth and cold areas of sensory dysfunction, mechanical thresholds using monofilaments and pin-prick, thermal thresholds including warmth and cold detection thresholds and heat pain threshold, with bilateral examination. Agreement and reliability were assessed by Bland-Altman plots, descriptive statistics, coefficients of variance, and intraclass correlation. Bland-Altman plots showed high variation on the surgical side. Intraclass coefficients ranged from 0.356 to 0.847 (moderate to substantial reliability). Between-patient variation was generally higher (0.9 to 14.5 SD) than within-patient variation (0.23 to 3.55 SD). There were no significant differences between pain and pain-free patients. The individual test-retest variability was higher on the operated side compared with the nonoperated side. The QST protocol reliability allows for group-to-group comparison of sensory function, but less so for individual follow-up after breast cancer surgery.

Distinct quantitative sensory testing profiles in nonspecific chronic back pain subjects with and without psychological trauma.

Psychological trauma is associated with an increased risk for chronification of nonspecific chronic back pain (nsCLBP) independent of posttraumatic stress disorder (PTSD). However, the mechanisms underlying the role of psychological trauma in nsCLBP are less clear than in PTSD. Therefore, this study considered whether psychological trauma exposure (TE) is accompanied by specific alterations in pain perception. The study included 56 participants with nsCLBP and TE (nsCLBP-TE), 93 participants with nsCLBP without TE (nsCLBP-W-TE), and 31 pain-free controls. All participants underwent a thorough clinical evaluation. The standardized quantitative sensory testing protocol of the "German Research Network on Neuropathic Pain" was used to obtain comprehensive profiles on somatosensory functions in painful (back) and non-painful areas (hand). The protocol consisted of thermal and mechanical detection as well as pain thresholds, vibration thresholds, and pain sensitivity to sharp and blunt mechanical stimuli. Psychological trauma was validated by structured clinical interview. Trauma-associated symptom severity, anxiety, and depressive symptomatology were assessed by self-report questionnaires. Differences in somatosensory function were seen only for pressure pain thresholds. Compared with controls, nsCLBP-TE revealed hyperalgesia generalized in space with lower thresholds in painful and non-painful areas, whereas nsCLBP-W-TE demonstrated localized alterations with decreased thresholds only in the pain-affected area of the back (P ≤ 0.006). Our findings suggest an augmented central pain processing in nsCLBP-TE (alterations in painful and non-painful areas), whereas nsCLBP-W-TE show only local changes (alterations only in the painful area) suggesting regional sensitization processes. This finding might explain why TE without PTSD is associated with an increased prevalence of chronic pain.

(126) Test-retest agreement of quantitative sensory testing 12 months after breast cancer surgery

Quantitative sensory testing (QST) examines psychophysical response to controlled, graded stimuli such as mechanical and thermal thresholds, and allows assessment of nerve damage. In the breast cancer population, 3 studies have used QST to examine persistent pain after breast cancer treatment (PPBCT), suggesting neuropathic pain being a prominent pain mechanism. However, QST reliability and validity has not been described in the postsurgical population. The aim of the present study was to assess 14 days test-retest reliability and variation of QST 12 months after breast cancer surgery. 32 patients were recruited from a larger prospective trial, scheduled for examination with QST 12 months after breast cancer surgery, and reexamined a week later. A standardized QST protocol was performed, including sensory mapping for mechanical, warmth and cold areas of sensory dysfunction, mechanical thresholds using monofilaments and pin-prick, and thermal thresholds including warmth and cold detection thresholds and heat pain threshold. Method reliability was assessed by Bland-Altman plots, descriptive statistics, coefficients of variance and intraclass correlation coefficients. 31 percent of the patients had pain ≥ 4 on a numerical rating scale, at rest, motion or pressure. Bland-Altman plots showed no systematic bias. T-tests showed very small differences on a group level. Variation coefficient was in the range 1 – 15%, and intraclass coeffients (ICC) ranged from 0.356 to 0.847 (moderate to almost perfect agreement). Between-subject variation (0.9 to 14.5 SD) was generally higher than within subject variation (0.23 to 3.55 SD).12 months after breast cancer surgery, our QST protocol showed moderate to perfect agreement (ICC), and low within subject variability. Thus, the protocol reliability allows for individual follow up and group-to-group comparison of sensory function.

Sensory correlates of pain in peripheral neuropathies

ObjectiveTo characterize sensory threshold alterations in peripheral neuropathies and the relationship between these alterations and the presence of pain. MethodsSeventy-four patients with length-dependent sensory axonal neuropathy were enrolled, including 38 patients with painful neuropathy (complaining of chronic, spontaneous neuropathic pain in the feet) and 36 patients with painless neuropathy. They were compared to 28 age-matched normal controls. A standardized quantitative sensory testing protocol was performed in all individuals to assess large and small fiber function at the foot. Large fibers were assessed by measuring mechanical (pressure and vibration) detection thresholds and small fibers by measuring pain and thermal detection thresholds. ResultsBetween patients with neuropathy and controls, significant differences were found for mechanical and thermal detection thresholds but not for pain thresholds. Patients with painful neuropathy and those with painless neuropathy did not differ regarding mechanical or thermal thresholds, but only by a higher incidence of thermal or dynamic mechanical allodynia in case of painful neuropathy. Pain intensity correlated with the alteration of thermal detection and mechanical pain thresholds. ConclusionsQuantitative sensory testing can support the diagnosis of sensory neuropathy when considering detection threshold measurement. Thermal threshold deterioration was not associated with the occurrence of pain but with its intensity. SignificanceThere is a complex relationship between the loss or functional deficit of large and especially small sensory nerve fibers and the development of pain in peripheral neuropathy.

Enhanced sensitivity to punctate painful stimuli in female patients with chronic low back pain

BackgroundChronic low back pain (CLBP) has been shown to be associated with various pathophysiological changes at several level of the sensorimotor system, pointing to a general hypersensitivity in CLBP patients. The aim of the present study was to investigate signs of generalized mechanical pain hypersensitivity in CLBP patients on the hand and on the painful site of the back.MethodsPinprick stimulation according to a validated standardized quantitative sensory testing protocol was used in 14 female CLBP patients and 14 healthy controls (HC) matched for sex and age. Stimulus response functions to pinprick stimulation on the skin were examined at the affected back and reference sites (hand palmar and hand dorsum). Data from CLBP patients were compared with HC and with reference data from the German Research Network on Neuropathic Pain.ResultsWe found significant differences in the stimulus response functions between CLBP patients and HC. Pain ratings to the pinpricks were increased for low and moderate pinprick stimuli in CLBP patients. Importantly, this kind of specific pinprick hyperalgesia was found not only for the affected body site (back), but also for the remote reference sites (hand dorsum and hand palmar).ConclusionsWe interpret our results as pointing to changes in the nociceptive processing in CLBP at higher levels of the neuraxis, possibly thalamus and/or attentional control, rather than changes of spinal processing. Alternatively, there might be a higher vulnerability to noxious stimulation in CLBP patients.

Anesthesia Literature Review

Studies on the cardioprotective effects of statins such as atorvastatin have proved mixed results. Two prospective, randomized controlled, single-blinded studies of patients scheduled to undergo elective coronary artery bypass graft surgery were conducted to determine the effects of 160 mg atorvastatin either 2 (study 1) or 12 (study 2) hr preoperatively and continued for 24 h after surgery. Although high-dose atorvastatin was not associated with significant side effects, no protective effects were observed, either. Serum troponin T and creatine kinase at all time-points in both studies were similar to controls (fig. 1). This study does not support the use of high-dose atorvastatin preoperatively for cardioprotection in low-risk patients currently taking statins and who are undergoing coronary artery bypass graft surgery.This 25-center trial randomized high-risk patients (n = 699) with severe aortic stenosis to undergo aortic valve replacement by transcatheter aortic valve replacement (TAVR); transapical or transfemoral approaches were used. The comparison group was open cardiac surgery. Although 30-day and 1-yr postvalve replacement outcomes were previously reported, the current paper described outcomes 2 yr after aortic valve replacement. There were no significant differences in 2-yr rates of mortality, cardiovascular mortality, or stroke in the two study groups (P &gt; 0.05). However, the presence of moderate or severe paravalvular leak was significantly increased in the TAVR group at 2 yr (6.9%vs. 0.9%; P &lt; 0.001). In the TAVR group, mild to severe paravalvular leak (P &lt; 0.001) and total aortic regurgitation (P = 0.006) were accompanied by significantly reduced 2-yr survival (fig. 2). This suggests that paravalvular leak after TAVR introduces a mortality risk that should be addressed by future studies and that should possibly be considered when TAVR patients present for other surgeries or procedures.The long-term impact of delirium experienced by patients in the intensive care unit (ICU) has not been well studied. A prospective study was conducted to examine the impact of delirium during ICU stay on health-related quality of life and cognitive function 18 months after ICU discharge. Using the Short Form-36v1 questionnaire, no differences were observed between patients with delirium (n = 272) and those without (n = 1,020). However, duration of delirium was correlated to problems with memory and names. This study suggests that delirium may play some role in long-term quality of life outcomes in ICU-survivors; however, additional studies are needed.Despite its known benefits, long-term sedation is associated with severe adverse effects. Two phase III multicenter, randomized, double-blind trials were conducted to determine the efficacy of dexmedetomidine versus midazolam (MIDEX trial, n = 500) or propofol (PRODEX trial, n = 498) in mechanically ventilated patients in the intensive care unit. Median durations of mechanical ventilation were not inferior for dexmedetomidine compared with midazolam or propofol (fig. 3). Rates of hypotension (P = 0.007) and bradycardia (P &gt; 0.001) were significantly higher in patients who received dexmedtomidine compared with midazolam. Although dexmedetomidine was found to be noninferior to midazolam and propofol in terms of sedation maintenance, it was associated with an increased rate of adverse effects. Therefore, dexmedetomidine does not present an improvement on preferred usual care for sedation of mechanically ventilated patients in the intensive care unit.Few investigators have studied the presence of bilateral sensory abnormalities in patients with chronic pain. The current study used the standardized quantitative sensory testing protocol to investigate somatosensory function on the painful and nonpainful side in healthy subjects (n = 209) and patients (n = 81) with unilateral neuropathic pain. Among healthy subjects, 36% showed a sensory abnormality for at least one quantitative sensory testing parameter, most of which were sensory gains. Nearly all patients in the neuropathic group (91%) had at least one quantitative sensory testing abnormality on the affected side, and 74% on the contralateral side. Some patients (35%) experienced a mixture of sensory gain and loss on the contralateral side. This study confirms that changes on the contralateral side in patients with unilateral neuropathic pain are common, and should be considered in the patient evaluation pathway.Radiculopathy occurs in a large portion of patients with low back pain and is generally associated with activation of inflammatory pathways. A multicenter, three-group, randomized, placebo-controlled trial was conducted in adults with recent (less than 6 months' duration) lumbosacral radiculopathy to evaluate the effects of epidural steroids, etanercept, or saline. Although not significant, patients who received epidural steroids demonstrated the greatest reduction in leg pain 1 month after the second injection (fig. 4). Epidural steroids also provided greater improvements in back pain. Therefore, larger studies with long-term follow-up are required to confirm the superiority of epidural steroids for patients with lumbosacral radiculopathy.

Test Order of Quantitative Sensory Testing Facilitates Mechanical Hyperalgesia in Healthy Volunteers

Quantitative sensory testing (QST) has become a widely used method to evaluate different submodalities of the somatic sensory system (predominantly) in patients with neuropathic pain. QST consists of 7 tests measuring 13 parameters in order to assess and quantify the perception of temperature, touch, pain, pressure, and vibration. The German Research Network on Neuropathic Pain implemented a standardized QST protocol including a defined testing order of the measurements. Accordingly, subjects tested with QST undergo thermal before mechanical testing. In the present study, we investigated the effect of testing order on the results of QST. Twenty healthy subjects were tested twice, 1 week apart with 2 different QST testing orders: the standardized testing order according to the German Research Network on Neuropathic Pain and a modified testing order in which mechanical stimuli were applied before thermal stimuli. For the test protocol that began with thermal testing, subjects exhibited signs of an increased mechanical perception: The mechanical pain sensitivity was significantly increased ( P = .001, Wilcoxon test) for each pinprick stimulator and the mechanical pain threshold was lowered by a factor of 2 when compared with the modified testing order in which mechanical parameters were tested at the beginning of the session without prior thermal stimulation. Thermal parameters were the same for both test-order paradigms. These data indicate that preceding mild thermal stimulation might lead to a sensitization to mechanical stimuli and thus to mechanical hyperalgesia. Alternative habituation mechanisms in the modified testing order resulting from repeated pinprick stimulation at the beginning should also be debated. QST is a helpful diagnostic tool but interpretation should be done with consideration of interaction between test parameters. Reference data are only valid in the testing order from which they are obtained. Perspective Present data showed that mechanical hyperalgesia followed thermal testing. This article demonstrates that the test order of quantitative sensory testing is relevant in interpreting the results obtained. Reference values are suitable in the test order from which they are obtained.

Reference data for quantitative sensory testing (QST): Refined stratification for age and a novel method for statistical comparison of group data

Clinical use of quantitative sensory testing (QST) requires standardization. The German research network on neuropathic pain (DFNS) solves this problem by defining reference data stratified for test site, gender and age for a standardized QST protocol. In this report we have targeted two further problems: how to adjust for age-related sensory changes, and how to compare groups of patients with the reference database. We applied a moving average across ages to define reference values per decade. This analysis revealed that women were more sensitive to heat pain independent of age. In contrast, functions were converging at older age for blunt pressure pain, but diverging for punctate mechanical pain (pin prick). The probability that an individual patient dataset is within the range of normal variability is calculated by z-transform using site-, gender- and age-specific reference data. To compare groups of patients with reference data, we evaluated two techniques: A: paired t-test versus fixed mean; i.e. the reference mean value is considered as the known population mean, B: non-paired t-test versus the reference dataset and number of cases restrained to the same number of cases as the patient data set. Simulations for various sample sizes and variances showed that method B was more conservative than method A. We present a simple way of calculating method B for data that have been z-normalized. This technique makes the DFNS reference data bank applicable for researchers beyond the DFNS community without a need for subsampling of subjects from the database.