Pain Detection Threshold Research Articles

Trajectories of cold but not mechanical sensitivity correspond with disability trajectories after whiplash injury.

Developmental trajectories for neck disability after whiplash injury have been identified. Their relationship to cold and mechanical sensitivity trajectories is not known. We aimed to (1) identify recovery trajectories of cold and mechanical sensitivity, (2) explore their codevelopment with disability trajectories, (3) identify predictors of sensitivity trajectories, and (4) explore codevelopment of cold and mechanical sensitivity trajectories. Participants (n = 233) were assessed at <1, 3, 6, and 12 months after whiplash injury. Outcomes were cold pain detection threshold (CPT at neck), pressure pain detection thresholds (PPT, neck C5, and tibialis anterior), and the Neck Disability Index. We used group-based trajectory models to identify postinjury recovery trajectories and multinominal logistic regression to explore associations between baseline characteristics and trajectory membership. We identified the following trajectory groups: CPT (low [50.0%], moderate [29.7%], and high [20.4%] sensitivity); PPT C5 (low [10.8%] and high [89.2%] sensitivity); and PPT tibialis anterior (low [23.9%], moderate [39.0%], and high [37.1%] sensitivity); all were stable over the 12 months. There was good correspondence between disability and cold sensitivity trajectory groups but not for mechanical sensitivity; cold and mechanical sensitivity trajectories were not well associated. Higher baseline pain predicted membership of the high cold sensitivity trajectory (RR 1.27, 95% CI 1.01-1.59) and hyperarousal symptoms predicted membership of the moderate cold sensitivity trajectory (RR 1.17, 95% CI 1.01-1.36). We found no associations between baseline characteristics and mechanical sensitivity. There is an interplay between cold allodynia, pain, and hyperarousal symptoms in development of ongoing disability after whiplash injury. Different mechanisms likely underlie cold and mechanical sensitivity.

Randomized, placebo-controlled study on the effects of intravenous GSK3858279 (anti-CCL17) on a battery of evoked pain tests in healthy participants.

C-C Motif Chemokine Ligand 17 (CCL17) is a chemokine that binds and signals through the G-protein coupled CC-chemokine receptor 4 and has been implicated in the development of inflammatory and arthritic pain. GSK3858279 is a high-affinity, first-in-class, monoclonal antibody, binding specifically to CCL17 and inhibiting downstream signaling. In this phase I, randomized, single-center, double-blind, placebo-controlled, three-period, incomplete-block crossover study (NCT04114656), the analgesic effects and safety of intravenous GSK3858279 were assessed in a battery of evoked acute pain assessments on healthy, adult (aged ≥18 years), male participants. Participants were randomized 1:1 to receive either one placebo (0.9% w/v NaCl) dose followed by two GSK3858279 doses (PAA treatment sequence), or one GSK3858279 dose followed by two placebo doses (APP treatment sequence). The co-primary end points were ultraviolet B heat pain detection threshold (°C), cold pressor time to pain tolerance threshold (PTT, sec), and electrical PTT (mA, single stimulus). Twenty-one participants were enrolled (PAA = 11; APP = 10). Mean age (standard deviation) was 29.3 (7.9) years for PAA, 31.1 (7.7) years for APP. No significant differences were observed in the analgesic effect between GSK3858279 and placebo for any end point. Exposure to GSK3858279 was similar between Period 1 (APP sequence), and Periods 2 and 3 (PAA sequence), with some GSK3858279 carry-over. Changes in serum CCL17 levels were consistent with the expected GSK3858279 activity. All drug-related adverse events were mild in intensity and caused no discontinuations. The absence of an efficacy signal in this acute pain model does not preclude efficacy in chronic pain states.

Pressure algometry in the general adult population: Age and sex differences.

Experimental pain studies have revealed inter-individual variations in pain perception that are influenced by age, sex, and country of origin. This study aimed to explore the age and sex differences in pressure pain thresholds within the Iranian general population. To assess the pressure pain thresholds, a handheld pressure algometer was applied bilaterally to the middle fingers of both hands. The participants also completed the short form of the McGill Pain Questionnaire to provide a clinical pain rating. This cross-sectional study included 1610 adult subjects (54.96% female, mean age 40.13 ± 10.18 years). The findings indicated that females generally exhibited lower pain thresholds than males when assessing pain detection and tolerance parameters (P < .001). Females also demonstrated a significant lower pressure thresholds and clinical pain ratings compared with men (P < .001). Additionally, significant differences were observed between age groups in terms of pain detection and tolerance thresholds (P = .02 and P = .03, respectively). However, the interaction between sex and age was not significant. No significant differences in pain detection thresholds were observed between the right and left hand (P = .11). This study underscores the potential utility of algometry as a valuable tool for objectifying pain in the Iranian population.

Children and adolescents with primary headaches exhibit altered sensory profiles – a multi-modal investigation

BackgroundPediatric headache is an increasing medical problem that has adverse effects on children’s quality of life, academic performance, and social functioning. Children with primary headaches exhibit enhanced sensory sensitivity compared to their healthy peers. However, comprehensive investigations including multimodal sensory sensitivity assessment are lacking. This study aimed to compare sensory sensitivity of children with primary headaches with their healthy peers across multiple sensory domains.MethodsThe study included 172 participants aged 6 to 17 years (M = 13.09, SD = 3.02 years; 120 girls). Of these 80 participants were patients with migraine, 23 were patients with tension-type headache, and 69 were healthy controls. The following sensory measures were obtained: Mechanical Detection Threshold (MDT), Mechanical Pain Threshold (MPT), Mechanical Pain Sensitivity (MPS), detection and pain threshold for Transcutaneous Electrical Nerve Stimulation (TENS), olfactory and intranasal trigeminal detection threshold, and odor identification ability. Sensory sensitivity was compared between groups with a series of Kruskal-Wallis tests. Binomial regression models were used to compare the relative utility of sensory sensitivity measures in classifying participants into patients and healthy controls, as well as into patients with migraine and tension-type headache.ResultsPatients with migraine had lower MPT measured at the forearm than patients with tension-type headaches and healthy controls. MPS was higher in patients with migraine than in healthy controls. All patients with headaches had lower detection threshold of TENS and higher olfactory sensitivity. Healthy controls showed increased intranasal trigeminal sensitivity. Scores in MPS, TENS, and olfactory and trigeminal thresholds were significantly predicting presence of primary headaches. Additionally, scores in MPT, olfactory and trigeminal threshold were positive predictors of type of headache.ConclusionsChildren with primary headaches exhibit different sensory profiles than healthy controls. The obtained results suggest presence of increased overall, multimodal sensitivity in children with primary headaches, what may negatively impact daily functioning and contribute to further pain chronification.Trial registrationThe study was registered in the German Registry of Clinical Trials (DRKS) DRKS00021062.

P111 Reliability of quantitative sensory testing, disease activity score 28, ultrasound and central aspects of pain questionnaire in individuals with rheumatoid arthritis

Abstract Background/Aims Disease Activity Score 28 (DAS28), ultrasound, quantitative sensory testing (QST) and central aspect of pain (CAP) questionnaire measure disease activity and pain hypersensitivity. We investigated their inter-rater and test-retest reliability in Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) participants. Methods Participants who attended the CAP-RA study visit and agreed to one or more reliability assessments were included. The same two raters completed all assessments, including clinical examination for DAS28, using a single blood sample per participant. QST modalities in the sequence: Pressure Pain detection Threshold (PPT) at the medial joint line of the most painful knee, tibialis anterior and contralateral brachioradialis, Temporal Summation (TS) at rectus femoris of the most painful knee and Conditioned Pain Modulation (CPM), with ischaemic arm pain conditioning and PPT at tibialis anterior. Ultrasound followed the Backhaus 7 protocol, plus the knee. Two trained sonographers scored each joint scan for grey scale (GS), power Doppler and a combined score (PDUS) using EULAR-OMERACT methodology. Joint scores were summated to give an overall score for GS, Doppler and PDUS. Participants could complete questionnaires at invitation, prior to and at baseline, 1-week post-baseline, prior to and at follow-up visit. Any combination of questionnaires completed within 7 days of each other assessed repeatability. Data were assessed for normality, interclass correlation coefficients, and Bland and Altman plots in R studio. Results 196 people were recruited into CAP-RA (median (IQR)) age 66 (58-75) y, 139 (75%) female, 190 (98%) white. 97 (49%) undertook study visits. Characteristics of the 66 people undertaking reliability did not significantly differ from the total population. Measurements are shown in Table 1. Moderate to excellent reliability was found across all measures except CPM (Table 1). The swollen joint count was the least reliable of the DAS28 components. Conclusion Measures of inflammatory disease activity and pain sensitivity are at least moderately reliable within a research context. Only low reliability for CPM might indicate imprecision, or reflect fluctuations in symptoms or pain sensitivity. High reliability of DAS28 and US might reflect relative stability of clinical signs of inflammation. Suppressing day-to-day fluctuations could reduce the unpredictability of rheumatoid arthritis. Disclosure S.L. Smith: None. V. Georgopoulos: None. O. Ifesemen: None. E. Ferguson: None. R.J. Wakefield: None. D. Wilson: None. P. Buckley: None. D. Platts: None. S. Ledbury: None. D.F. McWilliams: Grants/research support; Eli Lilly, Pfizer, GSK, Orion, UCB. D.A. Walsh: Grants/research support; Eli Lilly, Pfizer, GSK, Orion, UCB.

Age differences in pain sensitivity and effect of topical lidocaine on the tongue in healthy female subjects.

To assess the sensitivity and the effect of topical lidocaine on the tongue by quantitative sensory testing, comparing healthy middle-aged female subjects with healthy young female subjects. Sixteen healthy female subjects including eight in their fifties and eight in their twenties participated. They participated in two sessions at a 2-week interval in randomized order: lidocaine (experimental session) or placebo gel (placebo session) was applied on the tongue tip for 5min. The following parameters were taken on the tongue tip before and after application of the gel in each session: tactile detection threshold (TDT), filament-prick pain detection threshold (FPT), and numerical rating scale (NRS). An increase of both TDT and FPT and a decrease of NRS were found after lidocaine application in both middle-aged and young female subjects. In the elder females, an increase of TDT, FPT, and NRS was also found after placebo gel application. However, the changes were not statistically significant, except for FPT in middle-aged subjects. The reactions found after lidocaine application in middle-aged female subjects could be due to habituation as well as to the post-application effect of placebo gel. Placebo-induced changes appeared more pronounced in the elder females.

Influence of central aspects of pain on self-management in people with chronic low back pain

ObjectiveThis observational study investigated whether central aspects of pain are associated with self-management domains in individuals with chronic low back pain (CLBP) undertaking a pain management program. MethodsIndividuals with CLBP provided pain sensitivity and self-management data at baseline (n = 97) and 3-months (n = 87). Pressure pain detection threshold (PPT) at the forearm, temporal summation (TS) and conditioned pain modulation (CPM), Widespread Pain Index (WPI), and a Central Aspects of Pain factor (CAPf) were considered as central aspects of pain. Self-management was measured using the 8 domains of the Health Education Impact Questionnaire, as well as Pain Self Efficacy and Health Care Utilisation questionnaires. ResultsPPT, CPM, WPI and CAPf predicted worse performance in several self-management domains at 3-months (r = 0.21 to 0.54, p < 0.05 overall). In multivariable regression models (adjusted for baseline scores of self-management, depression, catastrophization, pain and fatigue) low PPT, high TS, and high CAPf at baseline predicted poorer self-management at 3 months (R2 =0.14 to 0.52, β = −0.37 to 0.35, p < 0.05). ConclusionsCentral aspects of pain are associated with impaired self-management, over and above effects of pain intensity, fatigue, depression and catastrophizing. Practice implicationsTreatments that target central aspects of pain might help improve self-management in people with CLBP.

The interrater and test-retest reliability of 3 modalities of quantitative sensory testing in healthy adults and people with chronic low back pain or rheumatoid arthritis.

Quantitative Sensory Testing (QST) modalities used to assess central pain mechanisms require different protocols in people with different musculoskeletal conditions. We aimed to explore the possible effects of musculoskeletal diagnosis and test site on QST interrater and test-retest reliability. The study included participants with rheumatoid arthritis (RA, n = 18; QST conducted on lower leg) and low back pain (LBP, n = 25; QST conducted on forearm), plus 45 healthy control participants (n = 20 QST on lower leg and n = 25 QST on forearm). Test-retest reliability was assessed from QST conducted 1 to 3 weeks apart. Quantitative sensory testing modalities used were pressure pain detection threshold (PPT) at a site distant to tissue pathology, temporal summation (TS), and conditioned pain modulation (CPM). Temporal summation was calculated as difference or ratio of single and repeated punctate stimuli and unconditioned thresholds for CPM used single or mean of multiple PPTs. Intraclass correlation coefficients (ICCs) were compared between different subgroups. High to very high reliability was found for all assessments of PPT and TS across anatomical sites (lower leg and forearm) and participants (healthy, RA, and LBP) (ICC ≥ 0.77 for PPT and ICC ≥ 0.76 for TS). Reliability was higher when TS was calculated as a difference rather than a ratio. Conditioned pain modulation showed no to moderate reliability (ICC = 0.01-0.64) that was similar between leg or forearm, and between healthy people and those with RA or LBP. PPT and TS are transferable tools to quantify pain sensitivity at different testing sites in different musculoskeletal diagnoses. Low apparent reliability of CPM protocols might indicate minute-to-minute dynamic pain modulation.

Effects of an afforestation activity on thermal and mechanical pain mechanisms: A clinical trial

Sensory stimulation has shown the capacity to modulate pain mechanisms. Yet, the optimal methods of sensory stimulation remain uncertain. Afforestation activities stand out as a potential stimulation method, as they allow individuals to interact with multisensory stimuli produced in green environments. Exposure to natural multisensory stimuli has been shown to induce neurobiological activations in pain-related brain areas in healthy populations. However, the possible impact of the natural multisensory stimuli on the pain mechanisms themselves is yet to be explored. This study aimed to investigate the potential effects of sensory stimulation experienced during participation in an afforestation program on thermal and mechanical pain mechanisms. A single-group, pretest-posttest clinical trial was used. Forty-seven healthy adults performed an afforestation activity for 90 minutes. Measurements included cold pain detection and tolerance thresholds via the Cold Pressor Test, wind-up and mechanical pain sensitivity through a pinprick stimulator, and pressure pain detection and tolerance thresholds utilizing pressure algometry. For both thermal and mechanical pain thresholds, pain intensity was assessed using the 101-point Numeric Rating Scale. The results showed significant reductions in the cold pain intensity at the moment of detection (p = .046), mechanical pain sensitivity (p ≤ .014), and increases in the thresholds of pressure pain detection (p = .005) and tolerance (p ≤ .046). Therefore, the interaction with natural multisensory stimuli could be a possible therapeutic strategy to positively modulate mechanical pain sensitivity and pressure pain thresholds.

Bullying Involvement and Physical Pain Between Ages 10 and 13 Years: Reported History and Quantitative Sensory Testing in a Population-Based Cohort

We aimed to quantify the prospective association between bullying and physical pain in a population-based cohort of adolescents. We assessed 4,049 participants of the 10 and 13 years waves of the Generation XXI birth cohort study in Portugal. Pain history was collected using the Luebeck pain screening questionnaire. A subsample of 1,727 adolescents underwent computerized cuff pressure algometry to estimate pain detection/tolerance thresholds, temporal pain summation and conditioned pain modulation. Participants completed the Bully Scale Survey and were classified as “victim only”, “both victim and aggressor”, “aggressor only”, or “not involved”. Associations were quantified using Poisson or linear regression, adjusted for sex and adverse childhood experiences. When compared to adolescents “not involved”, participants classified as “victim only” or “both victim and aggressor” at age 10 had higher risk of pain with psychosocial triggers, pain that led to skipping leisure activities, multisite pain, pain of higher intensity, and pain of longer duration, with relative risks between 1.21 (95% confidence interval: .99, 1.49) and 2.17 (1.57, 3.01). “Victims only” at age 10 had lower average pain detection and tolerance thresholds at 13 years (linear regression coefficients: −1.81 [−3.29, −.33] and −2.73 [−5.17, −.29] kPa, respectively), as well as higher pain intensity ratings (.37 [.07, .68] and .39 [.06, .72] mm), when compared with adolescents not involved. No differences were seen for the remaining bullying profiles or sensory measures. Our findings suggest that bullying may have long-term influence on the risk of chronic musculoskeletal pain and may interfere with responses to painful stimuli. PerspectiveWe found prospective evidence that bullying victimization in youth: 1) is more likely to lead to negative reported pain experiences than the reverse, 2) may have long-term influence on adverse pain experiences, and 3) may contribute to pain phenotypes partly by interfering with somatosensory responses to painful stimuli.

Effects of virtual reality on psychophysical measures of pain: superiority to imagination and nonimmersive conditions.

Virtual reality (VR) has been shown to be effective in pain management. However, to date, little is known about the mechanisms by which immersive experiences influence pain processing. The aim of this study was to investigate the direct effects of an immersive VR environment on the perception of experimental pain in individuals with chronic pain and pain-free controls. The immersion in a VR landscape was compared with mental imagery and a nonimmersive control condition. Using a randomized within-crossover design, pressure pain detection and tolerance thresholds, spatial and temporal summation (SSP, TSP), and conditioned pain modulation (CPM) were measured in 28 individuals with chronic pain and 31 pain-free controls using phasic cuff pressure on the legs. Direct comparison between the groups showed that although individuals with pain had significantly lower pain thresholds, reduced CPM effects, and increased TSP, the VR condition had the same pain-inhibitory effect on pain thresholds as in pain-free controls. Conditioned pain modulation effects were reduced by all conditions compared with baseline. There were no significant differences between conditions and baseline for TSP and SSP. Overall, pain modulatory effects were largest for VR and smallest for imagery. These results demonstrate that immersion in a VR environment has an increasing effect on pain thresholds, reduces pain inhibition in a CPM paradigm, and has no effects on TSP. This applies for participants with chronic pain and pain-free controls. These VR effects exceeded the effects of mental imagery on the nonimmersive control condition. This indicates that VR effectively modulates pain perception in both patients and controls irrespective of differences in pain perception.

Associations of Muscle Strength with Central Aspects of Pain: Data from the Knee Pain and Related Health in the Community (KPIC) Cohort.

Knee pain is associated with lower muscle strength, and both contribute to disability. Peripheral and central neurological mechanisms contribute to OA pain. Understanding the relative contributions of pain mechanisms to muscle strength might help future treatments. The Knee Pain and related health In the Community (KPIC) cohort provided baseline and year 1 data from people with early knee pain (n = 219) for longitudinal analyses. A cross-sectional analysis was performed with baseline data from people with established knee pain (n = 103) and comparative data from people without knee pain (n = 98). Quadriceps and handgrip strength indicated local and general muscle weakness, respectively. The indices of peripheral nociceptive drive were knee radiographic and ultrasound scores. The indices associated with central pain mechanisms were Pressure Pain detection Threshold (PPT) distal to the knee, and a validated self-report Central Aspects of Pain Factor (CAPF). The associations were explored using correlation and multivariable regression. Weaker quadriceps strength was associated with both high CAPF and low PPT at baseline. Year 1 quadriceps weakness was predicted by higher baseline CAPF (β = -0.28 (95% CI: -0.55, -0.01), p = 0.040). Weaker baseline and year 1 handgrip strength was also associated with higher baseline CAPF. Weaker baseline quadriceps strength was associated with radiographic scores in bivariate but not adjusted analyses. Quadriceps strength was not significantly associated with total ultrasound scores. Central pain mechanisms might contribute to muscle weakness, both locally and remote from the knee.

A systematic review of the psychometric properties of pressure pain detection threshold in evaluating mechanical pain threshold in people with hand or wrist injuries

PurposeThe aim of this study was to conduct a systematic review of the psychometric properties of Pressure Pain Detection Threshold (PPDT) measures in people with hand or wrist injuries. Study Design and MethodsMEDLINE, Embase, and CINAHL databases were searched to identify eligible studies evaluating psychometric properties of PPDT in samples composed of at least 50% of people with hand or wrist injury. The Consensus-based Standards for the Measurement of Health Instruments' risk of bias checklist was used to critically appraise the included studies, and qualitative synthesis was performed by pooling the results of all studies that presented the same measurement property using Grading of Recommendations, Assessment, Development, and Evaluation. ResultsFrom 415 studies, 11 relevant studies were identified. Of the 11 studies, four hand or wrist injuries were represented; carpal tunnel syndrome, distal radius fractures, osteoarthritis, and complex regional pain syndrome. Intra-rater reliability was considered sufficient (intraclass correlation coefficient 0.64-0.94), with small reported standard error of the mean values (5.3-39.2 kPa). Results of validity and responsiveness could not be synthesized due to heterogeneity. Risk of bias for reliability and measurement error was assessed as very good or adequate, whereas validity and responsiveness were doubtful or inadequate. Overall quality of evidence was low or very low for all measurement properties. ConclusionsInconsistent results and low quality evidence provide little confidence in the overall measurement properties of PPDT in a hand or wrist injury population. No criterion standard for pain further highlights complexities around pain measurement such that the results obtained from PPDT measures in clinical practice cannot be compared to a gold standard measure.

Sex Differences in Pain and Quantitative Sensory Testing in Patients With Rheumatoid Arthritis.

Women with rheumatoid arthritis (RA) have higher pain and worse functional outcomes compared to men, even when treated with similar medications. The objective of this study was to identify sex differences in pain intensity, pain interference, and quantitative sensory tests (QST), which are independent of inflammation, in patients with RA. This study is a post hoc analysis of participants in the Central Pain in Rheumatoid Arthritis cohort. Pain intensity was assessed using a 0-10 numeric rating scale. Pain interference was measured using a Patient-Reported Outcomes Measurement Information System computerized adaptive test. QST included pressure pain detection thresholds, temporal summation, and conditioned pain modulation. Women and men were compared using multiple linear regression, adjusted for age, education, race, research site, depression, obesity, RA disease duration, swollen joint count, and C-reactive protein. Mean ± SD pain intensity was 5.32 ± 2.29 among women with RA, compared to 4.60 ± 2.23 among men with RA (adjusted difference 0.83 [95% confidence interval (95% CI) 0.14, 1.53]). Women with RA had lower pressure pain detection thresholds at the trapezius (adjusted difference -1.22 [95% CI -1.73, -0.72]), wrist (adjusted difference -0.57 [95% CI -1.07, -0.06]), and knee (adjusted difference -1.10 [95% CI -2.00, -0.21]). No statistically significant differences in pain interference, temporal summation, and conditioned pain modulation were observed. Women reported higher pain intensity and lower pressure pain detection thresholds (higher pain sensitivity) than men. However, pain interference, temporal summation, and conditioned pain modulation did not differ between men and women.

Pain history and experimental pressure pain responses in adolescents: Results from a population-based birth cohort.

Sensitized pain mechanisms are often reported in musculoskeletal pain conditions, but population-based paediatric studies are lacking. We assessed whether adolescents with musculoskeletal pain history had evidence of increased responsiveness to experimental pressure stimuli. Data were from 1496 adolescents of the Generation XXI birth cohort. Pain history was collected using the Luebeck Pain Questionnaire (self-reported at 13, parent-reported at 7 and 10 years). Two case definitions for musculoskeletal pain were considered: (1) cross-sectional-musculoskeletal pain lasting more than 3 months at age 13 and (2) longitudinal-musculoskeletal pain at age 13 with musculoskeletal pain reports at ages 7 and/or 10. Lower limb cuff pressure algometry was used to assess pain detection and tolerance thresholds, conditioned pain modulation effects (CPM, changes in thresholds in the presence on painful conditioning) and temporal summation of pain effects (TSP, changes in pain intensity to 10 phasic painful cuff stimulations). Adolescents with musculoskeletal pain at age 13 plus a history of pain in previous evaluations (longitudinal definition) had lower pain tolerance thresholds compared to the remaining sample (40.2 v. 49.0 kPa, p = 0.02), but showed no differences in pain detection threshold, CPM effect and TSP effect. Pain sensitivity, CPM effects and TSP effects were not significantly different when the current pain only case definition (cross-sectional) was used. Adolescents with current musculoskeletal pain who had a history of pain since childhood had lower tolerance to cuff stimulation. This may suggest long-standing musculoskeletal pain since childhood may contribute to sensitisation, rather than the presence of current pain only. Repeated musculoskeletal pain up to age 13 years may contribute to higher pain sensitivity (particularly lowered pressure pain tolerance) in the general adolescent population. This does not seem to be the case when reported pain experiences are recent or when the outcomes are temporal pain summation or CPM. In this community-based paediatric sample, the vast majority showed no sign of altered pain processing, but a small fraction may reveal some pain sensitization at 13 years of age.

Chronic post-thoracotomy pain after lung cancer surgery: a prospective study of preoperative risk factors.

The objective of this longitudinal cohort study was to investigate if preoperative pain mechanisms, anxiety, and depression increase risk of developing chronic post-thoracotomy pain (CPTP) after lung cancer surgery. Patients with suspected or confirmed lung cancer undergoing surgery by either video-assisted thoracoscopic surgery or anterior thoracotomy were recruited consecutively. Preoperative assessments were conducted by: quantitative sensory testing (QST) (brush, pinprick, cuff pressure pain detection threshold, cuff pressure tolerance pain threshold, temporal summation and conditioned pain modulation), neuropathic pain symptom inventory (NPSI), and the Hospital Anxiety and Depression Scale (HADS). Clinical parameters in relation to surgery were also collected. Presence of CPTP was determined after six months and defined as pain of any intensity in relation to the operation area on a numeric rating scale form 0 (no pain) to 10 (worst pain imaginable). A total of 121 patients (60.2 %) completed follow-up and 56 patients (46.3 %) reported CPTP. Development of CPTP was associated with higher preoperative HADS score (p=0.025), higher preoperative NPSI score (p=0.009) and acute postoperative pain (p=0.042). No differences were observed in relation to preoperative QST assessment by cuff algometry and HADS anxiety and depression sub-scores. High preoperative HADS score preoperative pain, acute postoperative pain intensity, and preoperative neuropathic symptoms were was associated with CPTP after lung cancer surgery. No differences in values of preoperative QST assessments were found. Preoperative assessment and identification of patients at higher risk of postoperative pain will offer opportunity for further exploration and development of preventive measures and individualised pain management depending on patient risk profile.

Modulation of Pain Sensitivity by a Hyperventilatory Breathing Exercise and Cold Exposure Training.

Evidence indicates that healthy individuals who follow a training program comprised hyperventilatory breathing exercises and cold exposure can voluntarily activate their sympathetic nervous system and attenuate their systemic inflammatory response during experimental endotoxemia (intravenous administration of bacterial endotoxin). Furthermore, trained participants reported less endotoxemia-induced flu-like symptoms. However, it remained to be determined whether the effects on symptoms are due to the mitigated inflammatory response or involve direct analgesic effects of (elements of) the training program. In the present study, we used Nijmegen-Aalborg Screening Quantitative sensory testing (NASQ) to objectively map pain sensitivity using non-invasive stimuli to address this question. First, NASQ parameters were evaluated in 20 healthy volunteers before, during, and after the conduct of the hyperventilatory breathing exercise. Second, NASQ measurements were performed before and after 48 healthy volunteers followed different modalities of the training program: breathing exercise training, cold exposure training, the combination of both, or no training. Lastly, NASQ measurements were performed in these 48 subjects during experimental endotoxemia. Electrical pain detection thresholds increased during the breathing exercise (p = 0.001) as well as four hours afterwards (p = 0.03). Furthermore, cold exposure training resulted in lower VAS scores during hand immersion in ice water (p < 0.001). Systemic inflammation induced by administration of endotoxin nullified the decreased pain perception during the ice water test in subjects trained in cold exposure. A hyperventilatory breathing exercise decreases pain perception induced by an electrical stimulus. Furthermore, cold exposure training may decrease pain perception induced by hand immersion in ice water.

Investigation of pain sensitivity following 3 nights of disrupted sleep in healthy individuals.

Poor quality sleep is a common complaint among people with chronic pain. The co-occurrence of poor sleep quality and chronic pain often comes with increased pain intensity, more disability and a higher cost of healthcare. Poor sleep has been suggested to affect measures of peripheral and central pain mechanisms. To date, sleep provocations are the only models proven to affect measures of central pain mechanisms in healthy subjects. However, there are limited studies investigating the effect of several nights of sleep disruption on measures of central pain mechanisms. The current study implemented three nights of sleep disruption with three planned awakenings per night in 30 healthy subjects sleeping at home. Pain testing was conducted at the same time of day at baseline and follow-up for each subject. Pressure pain thresholds were assessed bilaterally on the infraspinatus and gastrocnemius muscles. Using handheld pressure algometry, suprathreshold pressure pain sensitivity and area were also investigated on the dominant infraspinatus muscle. Cuff-pressure pain detection and tolerance thresholds, temporal summation of pain and conditioned pain modulation were investigated using cuff-pressure algometry. Temporal summation of pain was significantly facilitated (p= 0.022), suprathreshold pain areas (p= 0.005) and intensities (p< 0.05) were significantly increased, and all pressure pain thresholds were decreased (p< 0.005) after sleep disruption compared to baseline. The current study found that three consecutive nights of sleep disruption at home induced pressure hyperalgesia and increased measures of pain facilitation in healthy subjects, which is consistent with previous findings. Poor quality of sleep is often experienced by patients with chronic pain, with the most common complaint being nightly awakenings. This exploratory study is the first to investigate changes in measures of central and peripheral pain sensitivity in healthy subjects after sleep disruptions for three consecutive nights without any restrictions on total sleep time. The findings suggest that disruptions to sleep continuity in healthy individuals can induce increased sensitivity to measures of central and peripheral pain sensitization.

Serum Metabolome Analysis Identified Amino-Acid Metabolism Associated With Pain in People With Symptomatic Knee Osteoarthritis – A Cross-Sectional Study

Osteoarthritis (OA) is the most common arthritis affecting synovial joints such as knees and hips of millions of people globally. Usage-related joint pain and reduced function are the most common symptoms experienced by people with OA. To improve pain management, there is a need to identify validated biomarkers predicting therapeutic responses in targeted clinical trials. Our study aimed to identify the metabolic biomarkers for pain and pressure pain detection thresholds (PPTs) in participants with knee pain and symptomatic OA using metabolic phenotyping. Metabolite and cytokine measurements were done on serum samples using LC-MS/MS (liquid gas chromatography integrated magnetic resonance mass spectrometry) and Human Proinflammatory panel 1 kit respectively. Regression analysis was done in a test (n = 75) and replication study (n = 79) to investigate the metabolites associated with current knee pain scores and pressure pain detection thresholds (PPTs). Meta-analysis and correlation were done estimating precision of associated metabolites and identifying relationship between significant metabolites and cytokines respectively. Acyl ornithine, carnosine, cortisol, cortisone, cystine, DOPA, glycolithocholic acid sulphate (GLCAS), phenylethylamine (PEA) and succinic acid were found to be significantly (FDR <.1) associated with pain scores in meta-analysis of both studies. IL-10, IL-13, IL-1β, IL2, IL8 and TNF-α were also found to be associated with the significant metabolites. Significant associations of these metabolites and inflammatory markers with knee pain suggests that targeting relevant pathways of amino acid and cholesterol metabolism may modulate cytokines and these could be targeted as novel therapeutics development to improve knee pain and OA management. PerspectiveForeseeing the global burden of knee pain in Osteoarthritis (OA) and adverse effects of current pharmacological therapies, this study is envisaged to investigate serum metabolites and molecular pathways involved in knee pain. The replicated metabolites in this study suggests targeting amino-acid pathways for better management of OA knee pain.

Quantitative Sensory Changes Following Posterior Spinal Fusion to Treat Adolescent Idiopathic Scoliosis.

Sensory changes surrounding the incision frequently develop after posterior spinal fusion (PSF) to treat adolescent idiopathic scoliosis (AIS). Anecdotally, patients may experience sensory changes on the chest wall. Such postsurgical sensory changes are not well described quantitatively. This study aims to evaluate the presence, intensity, and duration of mechanical sensory changes in AIS patients postoperatively. A prospective cohort of AIS patients, 10 to 21 years old, was followed. Quantitative sensory testing (QST) included touch detection threshold [mechanical detection threshold (MDT)] and pain detection threshold (MPT), using VonFrey monofilaments and pinprick stimulators. QST was performed at 3 sites at T6: the right and left chest at the nipple line and adjacent to the incision below the inferior angle of the scapula. QST at the thenar eminence was the control. QST was collected at baseline, 3 days, 1, and 6 months postoperative. Thirty-four patients (21% males; mean age: 14.9 years old; median preoperative curve: 58 degrees) completed all testing. Mean deformity correction was 64% (SD: 10.4). Adjacent to the incision site, MDT was significantly higher compared with baseline at 3 days and 1 month ( P < 0.001) but not at 6 months ( P = 0.19), whereas MPT was significantly higher at 3 days, ( P < 0.001), 1 month ( P < 0.001), and 6 months ( P = 0.001). For the chest wall in all patients, MPT was higher on the left chest at 3 days ( P = 0.04) and on the right chest at 3 days ( P = 0.022) and 1 month ( P = 0.05). For patients with right-sided curves, MDT ( P = 0.01) and MPT ( P = 0.015) overall were significantly higher on the concave side (left) chest postoperatively. PSF is associated with sensory disturbances that are detectable within days, persist at 1 month, and improve at 6 months postoperatively adjacent to the incision and on the chest wall. We suspect that these sensory changes are transient. Describing postoperative sensory changes will help us better set postoperative expectations for patients undergoing PSF. Level I.