Effectiveness of an anti-inflammatory diet versus low-fat diet for knee osteoarthritis: the FEAST randomised controlled trial protocol.

INTRODUCTION: Chronic inflammation plays a key role in knee osteoarthritis pathophysiology and increases risk of comorbidities, yet most interventions do not typically target inflammation. Our study will investigate if an anti-inflammatory dietary programme is superior to a standard care low-fat dietary programme for improving knee pain, function and quality-of-life in people with knee osteoarthritis. METHODS AND ANALYSIS: The eFEct of an Anti-inflammatory diet for knee oSTeoarthritis study is a parallel-group, assessor-blinded, superiority randomised controlled trial. Following baseline assessment, 144 participants aged 45-85 years with symptomatic knee osteoarthritis will be randomly allocated to one of two treatment groups (1:1 ratio). Participants randomised to the anti-inflammatory dietary programme will receive six dietary consultations over 12 weeks (two in-person and four phone/videoconference) and additional educational and behaviour change resources. The consultations and resources emphasise nutrient-dense minimally processed anti-inflammatory foods and discourage proinflammatory processed foods. Participants randomised to the standard care low-fat dietary programme will receive three dietary consultations over 12 weeks (two in-person and one phone/videoconference) consisting of healthy eating advice and education based on the Australian Dietary Guidelines, reflecting usual care in Australia. Adherence will be assessed with 3-day food diaries. Outcomes are assessed at 12 weeks and 6 months. The primary outcome will be change from baseline to 12 weeks in the mean score on four Knee injury and Osteoarthritis Outcome Score (KOOS4) subscales: knee pain, symptoms, function in daily activities and knee-related quality of life. Secondary outcomes include change in individual KOOS subscale scores, patient-perceived improvement, health-related quality of life, body mass and composition using dual-energy X-ray absorptiometry, inflammatory (high-sensitivity C reactive protein, interleukins, tumour necrosis factor-α) and metabolic blood biomarkers (glucose, glycated haemoglobin (HbA1c), insulin, liver function, lipids), lower-limb function and physical activity. ETHICS AND DISSEMINATION: The study has received ethics approval from La Trobe University Human Ethics Committee. Results will be presented in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000440729.

Conditioned pain modulation (CPM) paradigm type affects its sensitivity as a biomarker of fibromyalgia.

Fibromyalgia (FM) is a widespread chronic pain syndrome, possibly associated with the presence of central dysfunction in descending pain inhibition pathways. Conditioned Pain Modulation (CPM) has been proposed as a biomarker of FM. Nonetheless, the wide variety of methods used to measure CPM has hampered robust conclusions being reached. To clarify the validity of CPM as a biomarker of FM, we tested two CPM paradigms (parallel and sequential) in a sample of 23 female patients and 23 healthy women by applying test (mechanical) stimuli and conditioning (pressure cuff) stimuli. We evaluated whether CPM indices could correctly classify patients and controls, and we also determined the correlations between the indices and clinical variables such as symptomatology, disease impact, depression, quality of life, pain intensity, pain interference, fatigue and numbness. In addition, we compared the clinical status of CPM responders (efficient pain inhibitory mechanism) and non-responders. We observed that only parallel CPM testing correctly classified about 70% of patients with FM. In addition, more than 80% of healthy participants were found to be responders, while the rate was about 50% in the FM patients. The sequential CPM test was not as sensitive, with a decrease of up to 40% in the response rate for both groups. On the other hand, we did not observe any correlation between CPM measures and clinical symptoms. In summary, our findings demonstrate the influence of the CPM paradigm used and confirm that CPM may be a useful marker to complement FM diagnosis. However, the findings also cast doubts on the sensitivity of CPM as a marker of pain severity in FM.

Fentanyl Analogs Exert Antinociceptive Effects via Sodium Channel Blockade in Mice.

The formalin test is one approach to studying acute pain in rodents. Similar to formalin, injection with glutamate and veratrine can also produce a nociceptive response. This study investigated whether opioid-related compounds could suppress glutamate- and veratrine-induced nociceptive responses in mice at the same dose. The administration of morphine (3 mg/kg), hydromorphone (0.4 mg/kg), or fentanyl (0.03 mg/kg) suppressed glutamate-induced nociceptive response, but not veratrine-induced nociceptive response at the same doses. However, high doses of morphine (10 mg/kg), hydromorphone (2 mg/kg), or fentanyl (0.1 mg/kg) produced a significant reduction in the veratrine-induced nociceptive response. These results indicate that high doses are required when using morphine, hydromorphone, or fentanyl for sodium channel-related neuropathic pain, such as ectopic activity. As a result, concerns have arisen about overdose and abuse if the dose of opioids is steadily increased to relieve pain. In contrast, trimebutine (100 mg/kg) and fentanyl analog isobutyrylfentanyl (iBF; 0.1 mg/kg) suppressed both glutamate- and veratrine-induced nociceptive response. Furthermore, nor-isobutyrylfentanyl (nor-iBF; 1 mg/kg), which is a metabolite of iBF, suppressed veratrine-induced nociceptive response. Besides, the optimal antinociceptive dose of iBF, unlike fentanyl, only slightly increased locomotor activity and did not slow gastrointestinal transit. Cancer pain is a complex condition driven by inflammatory, neuropathic, and cancer-specific mechanisms. Thus, iBF may have the potential to be a superior analgesic than fentanyl.

Concurrent validity of dynamic bedside quantitative sensory testing paradigms in breast cancer survivors with persistent pain.

BACKGROUND: Studies on the concurrent validity of clinically applicable testing protocols for conditioned pain modulation (CPM) and temporal summation of pain (TSP) in breast cancer survivors (BCS) with persistent pain are lacking. OBJECTIVES: This study investigated the concurrent validity of two bedside protocols for CPM and TSP in comparison to a respective reference protocol. The participants' preferences for bedside CPM and TSP protocols were assessed. METHODS: Thirty BCS experiencing persistent pain were included in this study. Each participant underwent a reference test along with two bedside alternatives for assessing both TSP and CPM. For CPM, a cold pressor test (CPT) and blood pressure cuff (BPC) were used as conditioning stimulus. The test stimulus was elicited in parallel by pressure pain threshold after 45 and 90 s of conditioning at the lower limb. The CPM reference test consisted of parallel heat stimuli at the forearms using a two-thermode system. TSP was elicited using a von Frey monofilament (256 mN) and an algometer (98 kPa) at the affected site and opposite lower limb. The TSP reference test consisted of heat stimuli at the affected site and opposite lower limb. Participants' testing preference was examined using a purpose-designed questionnaire. Spearman's rank test examined the correlation between protocols. RESULTS: The two bedside CPM protocols were strongly correlated (r = 0.787-0.939, p < 0.005). A strong correlation was found between the BPC protocol and reference test using the relative effect magnitude (r = 0.541-0.555, p < 0.005). The bedside TSP protocols were moderately correlated with each other only at the lower limb using absolute change scores (r = 0.455, p = 0.012). No significant correlation was found between the bedside and reference TSP protocols. CONCLUSION: The significantly moderate to very strong correlations between the bedside protocols validate their interchangeability. Researchers and clinicians should be able to choose which bedside protocol they utilize; however, participants favored the use of a BPC and algometer for the evaluation of CPM and TSP, respectively.

COMPARISON THE EFFICACY OF DRY NEEDLING AND ISCHEMIC COMPRESSION METHODS IN MIYOFASCIAL PAIN SYNDROME: A RANDOMIZED TRIAL.

Myofascial pain syndrome (MPS) is the most common in the musculoskeletal disease. Dry needling techniques and ischemic compression are the most common applications. We aimed to compare the efficacy of dry needling and ischemic compression methods on pain, cervical range of motion and disability in myofascial pain syndrome. This is a randomized, controlled study. 98 patients with MPS were randomly assigned into three groups. Group1 received dry needling (n=33), group 2 (n=33) received ischemic compression and group 3 (n=32) received combined with dry needling and ischemic compression inventions. Additionally, all patients were given neck exercise programs including isotonic, isometric, and stretching. The severity of the pain was measured by visual analog scale (VAS). The pressure pain threshold (PPT) and cervical range of motion (ROM) were also recorded. Disability was assessed by the Neck Pain Disability Scale. All assessments were performed before the treatment and one month and three months after the treatment. There were statistically significant improvements in VAS, PPT, cervical ROM, and disability scores after one and three months in all groups compared to pre-treatment results (p<0.05). After three months of follow-up, statistically significant differences were observed in all parameters between the groups (p<0.05) except cervical ROM (p>0.05). Myofascial pain syndrome in patients with ischemic compression and dry needling effective treatment methods are shown separately in our study to be more effective when used together.

Measurements of pupillary unrest using infrared pupillometry fail to detect changes in pain intensity in patients after surgery: a prospective observational study.

PURPOSE: The pupil displays chaotic oscillations, also referred to as pupillary unrest in ambient light (PUAL). As pain has previously been shown to increase pupillary unrest, the quantitative assessment of PUAL has been considered a possible tool to identify and quantify pain. Nevertheless, PUAL is affected by various states, such as vigilance, cognitive load, or emotional arousal, independent of pain. Furthermore, systematically applied opioids are known to reduce PUAL, thus potentially limiting its usefulness to detect pain or changes in pain intensity. To test the hypothesis that PUAL can reliably identify changes in pain intensity in a clinical setting, we measured PUAL in patients experiencing substantial pain relief when regional anesthesia interventions were applied after surgery. METHODS: We conducted an observational study at an academic surgery centre following institutional review board approval. Eighteen patients with unsatisfactory pain control following surgery underwent regional anesthesia procedures to improve pain control. We used infrared pupillometry to assess pupillary unrest before and after the regional block. We then compared the changes in pupillary unrest with the changes in pain scores (numeric rating scale [NRS], range 0-10). RESULTS: Eighteen patients received epidural anesthesia (n = 14) or peripheral nerve blocks (n = 4), resulting in improvement of mean (standard deviation [SD]) NRS pain scores from 7.2 (1.7) to 1.9 (1.8) (difference in means, -2.2; 95% confidence interval [CI], -6.3 to -4.1; P < 0.001). Nevertheless, pupillary unrest did not change as pain decreased; the mean (SD) PUAL was 0.113 (0.062) before analgesia and 0.112 (0.068) after analgesia (difference in means, -0.001; 95% CI, -0.018 to 0.015; P = 0.88). CONCLUSION: In this prospective observational study, pupillometric measurements of pupillary unrest did not identify changes in pain intensity in a postoperative, predominantly opioid-exposed patient population. While the sample size was small, the use of measurements of pupillary unrest to detect and quantify pain has to be questioned.

RéSUMé: OBJECTIF: La pupille affiche des oscillations chaotiques, également appelées fluctuations du diamètre pupillaire (FDP). Comme il a déjà été démontré que la douleur augmente les troubles pupillaires, l'évaluation quantitative des FDP a été envisagée comme outil potentiel pour identifier et quantifier la douleur. Néanmoins, les FDP sont affectées par divers états, tels que la vigilance, la charge cognitive ou l'excitation émotionnelle, indépendamment de la douleur. De plus, nous savons que l'application systématique d'opioïdes réduit les FDP, ce qui limite potentiellement leur utilité pour détecter la douleur ou les changements d'intensité de la douleur. Pour tester l'hypothèse selon laquelle les FDP permettent d'identifier de manière fiable les changements dans l'intensité de la douleur dans un cadre clinique, nous avons mesuré les FDP chez les patient·es manifestant un soulagement substantiel de la douleur lorsque des interventions d'anesthésie régionale ont été appliquées après la chirurgie. MéTHODE: Nous avons mené une étude observationnelle dans un centre de chirurgie universitaire après avoir obtenu l'approbation du comité d'éthique indépendant. Dix-huit patient·es dont le contrôle de la douleur n'était pas satisfaisant à la suite d'une intervention chirurgicale ont bénéficié d'interventions d'anesthésie régionale pour améliorer le contrôle de la douleur. Nous avons utilisé la pupillométrie infrarouge pour évaluer les fluctuations du diamètre pupillaire avant et après le bloc régional. Nous avons ensuite comparé les changements dans les fluctuations pupillaires avec les changements dans les scores de douleur (échelle d'évaluation numérique [EVA], plage de 0 à 10). RéSULTATS: Dix-huit patient·es ont reçu une anesthésie péridurale (n = 14) ou des blocs nerveux périphériques (n = 4), ce qui a entraîné une amélioration des scores de douleur moyens (écart type [ET]) sur l'EVA de 7,2 (1,7) à 1,9 (1,8) (différence de moyennes, −2,2 ; intervalle de confiance [IC] à 95 %, −6,3 à −4,1; P < 0,001). Néanmoins, les fluctuations du diamètre pupillaire n'ont pas changé à mesure que la douleur diminuait; la moyenne (ET) des FDP était de 0,113 (0,062) avant l'analgésie et de 0,112 (0,068) après l'analgésie (différence de moyennes, −0,001; IC 95 %, −0,018 à 0,015; P = 0,88). CONCLUSION: Dans cette étude observationnelle prospective, les mesures pupillométriques des fluctuations du diamètre pupillaire n'ont pas permis d'identifier de changements dans l'intensité de la douleur dans une population de patient·es postopératoires, principalement exposé·es aux opioïdes. Bien que la taille de l'échantillon soit petite, l'utilisation de mesures des fluctuations du diamètre pupillaire pour détecter et quantifier la douleur doit être remise en question.

Validation of the Oswestry Disability Index in Adult Spinal Deformity.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To examine the validity of the Oswestry Disability Index (ODI) in patients with adult spinal deformity (ASD) treated with surgery. BACKGROUND: The ODI is a patient-reported outcome measure of low back pain and disability. Although nearly ubiquitous in ASD research, the measure has not been validated in this patient population. PATIENTS AND METHODS: A registry of patients with ASD was queried for baseline and 1-year PROM data, including the ODI, the Scoliosis Research Society-22r (SRS-22r), and the Patient Reported Outcomes Measurement Information System-Pain Interference (PI) and Physical Function (PF) CATs. Internal reliability was assessed with Cronbach alpha, where values ≥0.7 are considered reliable. Validity was assessed with Spearman correlation coefficients calculated for the ODI against validated Patient-Reported Outcomes Measurement Information System (PROMIS)-PI and PF, and legacy measures SRS-Pain and SRS-Activity. Responsiveness to change was measured with the adjusted effect size. RESULTS: A total of 325 patients were enrolled, with 208 completing baseline and 1-year patient-reported outcome measures. The majority (149, 72%) were females and White (193, 93%), median Charlson Comorbidity Index 0 (interquartile range: 0-2). The majority of cases included sagittal plane deformity [mean T1PA: 24.2° (13.9)]. Cronbach alpha showed excellent internal reliability (baseline = 0.89, 1 yr = 0.90). ODI was valid, with strong correlations between PROMIS-PI, PROMIS-PF, SRS-Pain, and SRS-Activity at baseline and 1-year follow-up. All measures were responsive to change, with the ODI showing greater responsiveness than PROMIS-PI, PROMIS-PF, and SRS-Activity. CONCLUSIONS: The ODI is a valid measure of disability as measured by pain and function in patients with ASD. It is responsive to change in a manner not different from validated PROMIS-CAT or the SRS-22r legacy measure. It is multidimensional, however, as it assesses both pain and function simultaneously. It does not measure disability related to self-image and may not account for all disease-related disability in patients with ASD.

Anwendbarkeit, Wiederholbarkeit und Zuverlässigkeit der deutschen Version der Glasgow Composite Measured Pain Scale - feline während der Einführungsphase in eine KleintierklinikApplicability, reproducibility, and reliability of the German version of the Glasgow composite measured pain scale - feline during implementation into a small animal clinic. / Anwendbarkeit, Wiederholbarkeit und Zuverlässigkeit der deutschen Version der Glasgow Composite Measured Pain Scale ­ feline während der Einführungsphase in eine KleintierklinikApplicability, reproducibility, and reliability of the German version of the Glasgow composite measured pain scale ­ feline during implementation into a small animal clinic.

OBJECTIVE: The aim of the study was to evaluate reproducibility and practicality of the German version of the Glasgow composite measured pain scale - feline, during its implementation into a German veterinary hospital. MATERIAL AND METHODS: The study comprised of 2 parts. Participation of veterinary professionals was voluntary. During part 1, 15 staff members (all rater=AR) with variable clinical experience (nurses, interns, junior clinician, senior clinicians), from 4 disciplines (anesthesia, internal medicine, surgery, neurology), and one main investigator (AC), pain scored 45 diseased cats and 10 healthy cats. Part 2 was an online survey, evaluating the practical experience of participants during part 1 and asking for suggestions to improve the scale and process of pain assessment. For part 1 normal distribution of data was tested by Shapiro-Wilk-Test and histograms. Intrarater and interrater reliability were evaluated by calculating the intraclass-correlation. Statistical analysis of part 2 used descriptive methods. RESULTS: The interrater reliability was moderate (ICC AR : 0.59) and the intrarater reliability was good (ICC AC : 0.88). The pain scores of cats with medical (AR: 3.06±2.33, AC 3.52±2.34) and surgical disease (AR: 3.78±2.38, AC: 4.02±2.72) showed no significant difference. All healthy cats were classified as "not painful" (AR: 0.77±0.67, AC: 1.09±0.83). Clinical experience of the rater did not significantly influence pain scores. The GCMPS-F was judged as easy to use and as helpful tool for cats with unclear pain conditions. CONCLUSION: The GCMPS-F had a good acceptance and moderate interrater reliability. CLINICAL RELEVANCE: Using the German version of the GCMPS-F, veterinary professionals from different disciplines and with different grades of specialisation can reliably assess pain levels in cats without prior extensive training.

Evidence-Based Pain Assessment in Nonverbal Palliative Care Patients.

BACKGROUND: Central to palliative care is the early assessment and treatment of pain, whether physical, psychosocial, or spiritual. Nonverbal palliative care patients are at risk for inadequate pain assessment leading to prolonged suffering. AIMS: The purpose of this project was to implement and evaluate an evidence-based pain assessment tool for nonverbal palliative care patients. DESIGN: The Iowa Model Revised: Evidence-Based Practice to Promote Excellence in Healthcare and the Implementation Strategies for Evidence-Based Practice Guide provided the guiding frameworks. SETTINGS: On a six-bed adult inpatient Palliative Care Unit (PCU). PARTICIPANTS/SUBJECTS: Nonverbal palliative care patients. METHODS: Evidence supported use of the Multidimensional Objective Pain Assessment Tool (MOPAT) for nonverbal patients receiving palliative care. During an eight-week pilot, nurses recorded pain assessments on a paper form and trended pain scores over a 24-hour period. Evaluation included knowledge, attitudes, and behaviors pre- and post-pilot and was subsequently used in a Precision Implementation Approach to promote adoption. RESULTS: Nurses' attitudes toward palliative care pain assessment improved in all items on the evaluation tools. Pain was assessed using MOPAT for 74% of nonverbal palliative care patients and 88% of patients had linked pain interventions to MOPAT scores. CONCLUSIONS: MOPAT is the only valid evidence-based pain assessment tool for nonverbal patients receiving palliative care. This project led to successful adoption of the MOPAT within the PCU.

Relationship Between Central Sensitization-Related Symptoms and Pain-Related Disability After Cervical Spine Surgery: A Structural Equation Model.

BACKGROUND: It is unknown if central sensitization (CS)-related symptoms have an intermediate role that might explain how disability develops from pain after cervical spinal surgery. AIMS: The study aim was to investigate the role of CS-related symptoms in the relationship between pain and disability reported after cervical spinal surgery. DESIGN: Cross-sectional study. SETTINGS: Tertiary care spinal surgery center. PARTICIPANTS/SUBJECTS: The participants included individuals with a cervical degenerative condition who had undergone surgery. METHODS: The following patient-reported outcome measures were evaluated: (1) Numerical Rating Scale; (2) Neck Disability Index; and (3) Short Form of the Central Sensitization Inventory. A hypothesized model containing the CS-related symptoms and the relationships between pain and disability was constructed and tested by structural equation modeling. RESULTS: Questionnaires were mailed to 280 individuals, and responses were obtained from 145 participants. Of these respondents, 99 (68.3%) were males and 46 (31.7%) were females, with a mean age of 64.4 ± 12.3 years. The latent variable for pain, represented by the neck (coefficient: 0.856, p < .001) and upper limb pain (0.568, p < .001), influenced CS-related symptoms (coefficient: 0.504, p < .001). Pain directly affected disability (coefficient: 0.497, p < .001) and indirectly through CS-related symptoms. Bootstrap analysis confirmed this indirect effect (point estimate: 2.85, 95% confidence interval: 1.04 to 6.30, p = .04). CONCLUSIONS: The results revealed that neck and upper limb pain affected disabilities both directly and through CS-related symptoms. Future research should focus on the efficacy of biopsychosocial approaches for patients after cervical spine surgery with a high risk of disability due to CS-related symptoms.

Muscle Pressure Correlates With Pain Levels in Fibromyalgia Patients.

BACKGROUND/OBJECTIVE: We evaluated patients with fibromyalgia syndrome (FMS) to determine whether there is a correlation between pain scores based on a 0- to 10-point visual analog scale (VAS) and muscle pressure. METHODS: One hundred forty-two patients who satisfied the American College of Rheumatology classification criteria for FMS and 38 non-FMS controls comprised the study groups. Muscle pressure was measured in mm Hg using a pressure gauge attached to a no. 22 needle inserted into the midportion of the trapezius muscle. The muscle pressure was then correlated with the VAS pain score of 0 to 10, some with an increment of 0.5. A second muscle pressure was obtained from 19 patients at a subsequent visit, which was compared with their pain scores. RESULTS: The mean (SD) pain score for 142 patients with FMS was 6.6 (SD, 1.84) on a 0- to 10-point VAS. The mean pain score in the non-FMS subjects was 0.7 (SD, 1.26). The mean muscle pressure in the FMS group was 32.9 (SD, 6.57) mm Hg. The mean muscle pressure in the non-FMS subjects was 10.6 (SD, 3.85) mm Hg. The calculated Pearson correlation coefficient for muscle pressure versus pain score was 0.8312 ( p < 0.0001). This indicates a highly significant association between subjects' muscle pressure and pain scores. For the repeat muscle pressures, the change in muscle pressure was correlated with the change in pain score, and the resulting Pearson correlation coefficient was 0.9255 ( p < 0.0001). These results again indicate a highly significant association between subjects' muscle pressure and pain scores. CONCLUSION: The results show that increased muscle pressure may be a significant cause of pain in FMS, and the etiology of the pain may have a large peripheral component in addition to a centralized origin of the pain.

Increased nociceptive behaviors and spinal c-Fos expression in the formalin test in a rat repeated cold stress model.

Repeated cold stress (RCS) can trigger the development of fibromyalgia (FM)-like symptoms, including persistent deep-tissue pain, although nociceptive changes to the skin have not been fully characterized. Using a rat RCS model, we investigated nociceptive behaviors induced by noxious mechanical, thermal, and chemical stimuli applied to plantar skin. Neuronal activation in the spinal dorsal horn was examined using the formalin pain test. In rats exposed to RCS, nociceptive behavioral hypersensitivity was observed in all modalities of cutaneous noxious stimuli: the mechanical withdrawal threshold was decreased, and the heat withdrawal latency was shortened one day after the cessation of stress. The duration of nocifensive behaviors in the formalin test was prolonged in phase II but not in phase I. The number of c-Fos-positive neurons increased in the entire dorsal horn laminae I-VI, ipsilateral, but not contralateral, to formalin injection at the L3-L5 segments. The duration of nocifensive behavior in phase II was significantly and positively correlated with the number of c-Fos-positive neurons in laminae I-II. These results demonstrate that cutaneous nociception is facilitated in rats exposed to RCS for a short time and that the spinal dorsal horn neurons are hyperactivated by cutaneous formalin in the RCS model.

Comparing pain intensity rating scales in acute postoperative pain: boundary values and category disagreements.

Pain intensity assessment scales are important in evaluating postoperative pain and guiding management. Different scales can be used for patients to self-report their pain, but research determining cut points between mild, moderate and severe pain has been limited to studies with < 1500 patients. We examined 13,017 simultaneous acute postoperative pain ratings from 913 patients taken at rest and on activity, between 4 h and 48 h following surgery using both a verbal rating scale (no, mild, moderate or severe pain) and 0-100 mm visual analogue scale. We determined the best cut points on the visual analogue scale between mild and moderate pain as 35 mm, and moderate and severe pain as 80 mm. These remained consistent for pain at rest and on activity, and over time. We also explored the presence of category disagreements, defined as patients verbally describing no or mild pain scored above the mild/moderate cut point on the visual analogue scale, and patients verbally describing moderate or severe pain scored below the mild/moderate cut point on the visual analogue scale. Using 30 and 60 mm cut points, 1533 observations (12%) showed a category disagreement and using 35 and 80 mm cut points, 1632 (13%) showed a category disagreement. Around 1 in 8 simultaneous pain scores implausibly disagreed, possibly resulting in incorrect pain reporting. The reasons are not known but low rates of literacy and numeracy may be contributing factors. Understanding these disagreements between pain scales is important for pain research and medical practice.

Identifying clusters of objective functional impairment in patients with degenerative lumbar spinal disease using unsupervised learning.

OBJECTIVES: The five-repetition sit-to-stand (5R-STS) test was designed to capture objective functional impairment (OFI), and thus provides an adjunctive dimension in patient assessment. It is conceivable that there are different subsets of patients with OFI and degenerative lumbar disease. We aim to identify clusters of objectively functionally impaired individuals based on 5R-STS and unsupervised machine learning (ML). METHODS: Data from two prospective cohort studies on patients with surgery for degenerative lumbar disease and 5R-STS times of ≥ 10.5 s-indicating presence of OFI. K-means clustering-an unsupervised ML algorithm-was applied to identify clusters of OFI. Cluster hallmarks were then identified using descriptive and inferential statistical analyses. RESULTS: We included 173 patients (mean age [standard deviation]: 46.7 [12.7] years, 45% male) and identified three types of OFI. OFI Type 1 (57 pts., 32.9%), Type 2 (81 pts., 46.8%), and Type 3 (35 pts., 20.2%) exhibited mean 5R-STS test times of 14.0 (3.2), 14.5 (3.3), and 27.1 (4.4) seconds, respectively. The grades of OFI according to the validated baseline severity stratification of the 5R-STS increased significantly with each OFI type, as did extreme anxiety and depression symptoms, issues with mobility and daily activities. Types 1 and 2 are characterized by mild to moderate OFI-with female gender, lower body mass index, and less smokers as Type I hallmarks. CONCLUSIONS: Unsupervised learning techniques identified three distinct clusters of patients with OFI that may represent a more holistic clinical classification of patients with OFI than test-time stratifications alone, by accounting for individual patient characteristics.

Construct validity, responsiveness and reliability of the Feline Grimace Scale in kittens.

OBJECTIVES: The aim of the present study was to investigate the construct validity, responsiveness and reliability of the Feline Grimace Scale (FGS) in kittens. METHODS: A total of 36 healthy female kittens (aged 10 weeks to 6 months) were included in a prospective, randomized, blinded study. Video recordings of all kittens were made before and 1 and 2 h after ovariohysterectomy using an opioid-free injectable anesthetic protocol with or without multimodal analgesia. Additional recordings were taken before and 1 h after administration of rescue analgesia (buprenorphine 0.02 mg/kg IM) to painful kittens. Screenshots of facial images were collected from the video recordings for FGS scoring. Four observers blinded to treatment groups and time points scored 111 randomized images twice with a 5-week interval using the FGS. Five action units (AUs) were scored (ear position, orbital tightening, muzzle tension, whiskers position and head position; 0-2 each). Construct validity, responsiveness, and inter- and intra-rater reliability were evaluated using linear models with Benjamini-Hochberg correction, Wilcoxon signed-rank test and single intraclass correlation coefficients (ICCsingle), respectively (P <0.05). RESULTS: FGS total ratio scores were higher at 1 and 2 h after ovariohysterectomy (median [interquartile range, IQR]: 0.30 [0.20-0.40] and 0.30 [0.20-0.40], respectively) than at baseline (median [IQR]: 0.10 [0.00-0.30]) (P <0.001). FGS total ratio scores were lower after the administration of rescue analgesia (median [IQR] before and after rescue analgesia) 0.40 [0.20-0.50] and 0.20 [0.10-0.38], respectively (P <0.001). Inter-rater ICCsingle was 0.68 for the FGS total ratio scores and 0.35-0.70 for all AUs considered individually. Intra-rater ICCsingle was 0.77-0.91 for the FGS total ratio scores and 0.55-1.00 for all AUs considered individually. CONCLUSIONS AND RELEVANCE: The FGS is a valid and responsive acute pain-scoring instrument with moderate inter-rater reliability and good to excellent intra-rater reliability in kittens.

Use of Wearable Sensor Device and Mobile Application for Objective Assessment of Pain in Post-surgical Patients: A Preliminary Study.

Effective post-operative pain management requires an accurate and frequent assessment of the pain experienced by the patients. The current gold-standard of pain assessment is through patient self-evaluation (e.g., numeric rating scale, NRS) which is subjective, prone to recall-bias, and does not provide comprehensive information of the pain intensity and its trends. We conducted a study to explore the potential of wearable biosensors and machine learning-based analysis of physiological parameters to estimate the pain intensity. The results from our study of post-operative knee surgery patients monitored over a period of 30 days demonstrate the feasibility of the system in ambulatory setting, with a substantial agreement (Cohen's Kappa = 0.70, 95% CI 0.68-0.72) between the pain intensity estimation and the patient reported numerical rating scale. Therefore, the wearable biosensors coupled with the machine learning-derived pain estimation are capable of remotely assessing the pain intensity.

Predicting Pain Intensity after Mandibular Third Molar Surgery using Cold Pressor Testing: A Quasi-Experimental Study.

BACKGROUND: Patients complain differently about their experiences of post-operative pain. However, clinicians are often guided by their own viewpoints despite the highly subjective nature of pain resulting in suboptimal post-operative pain management. This impacts negatively on the quality of life of patients in the immediate post-operative period. Investigating patients' pain behavior in the pre-operative period may therefore help to predict the intensity of post-operative pain, thereby assisting in identifying patients who are at risk of greater pain after third molar surgery, and allocating extra resources for pain control. AIM: This study aims to predict the intensity of pain after third molar surgery by correlating post-operative pain perception with the sensory-discriminative dimension and affective response to a cold pressor stimulus. MATERIALS AND METHODS: This study is a quasi-experimental study that was conducted in the oral surgery clinic of (name of hospital in the title page). The procedure was undertaken in an isolated clinic cubicle with well-controlled room temperature and minimal distraction. Study participants were recruited by convenience sampling. Forty-three consenting participants, 20 years and above, who met eligibility criteria were subjected to pre-operative cold pressor testing. Subsequently, third molar surgery was done and post-operative pain intensity was recorded at specific intervals. Data analyses were completed using IBM SPSS version 25. The Kolmogorov-Smirnov (KS) test was used to test for normality of continuous variables. Ordinal regression was used to test for contributory value of pre-operative measurement while Spearman's rank correlation test was used to test their degree of relationships with post-operative pain P < 0.05. RESULT: The median pain threshold was 20 s (Interquartile Range, IQR 12.75-32.25) and the median pain tolerance was 33 s (IQR = 23.00-54.00) from the cold pressor test. The peak median pain score in this study was reached at 3-h after the last stitch. There was a statistically significant predictive effect of both variables on post-operative pain at 3-h. CONCLUSION: Sensory-discriminative dimension and affective response to cold pressor test are significant predictors of peak post-operative pain after impacted mandibular third molar surgery.

Serum VEGF and CGRP Biomarkers: Relationships with Pain Intensity, Electric Pain, Pressure Pain Threshold, and Clinical Symptoms in Fibromyalgia-An Observational Study.

Fibromyalgia (FM) is a multifactorial syndrome, mainly characterized by chronic widespread pain, whose physiopathology is yet to be determined. Reliable biomarkers for FM and how they are associated with the symptomatology have not yet been identified. We aimed to examine the relationships among serum vascular endothelial growth factor (VEGF) and calcitonin gene-related peptide (CGRP) levels with clinical manifestations and pain-related variables in women with FM. We conducted an observational case study with forty-seven women diagnosed with FM. Serum VEGF and CGRP levels were spectrophotometrically analyzed. We used questionnaires to measure the impact of FM and the degree of central sensitization, fatigue, and anxiety. We also assessed pain intensity, electric pain threshold and magnitude, and pressure pain threshold (PPT) in tender points. The linear regression analysis adjusting for age, menopause status, and body mass index showed that serum VEGF levels were significantly associated with the PPTs of non-dominant trapezius (ß = 153.418; p = 0.033), non-dominant second metacarpal (ß = 174.676; p = 0.008) and dominant tibialis anterior (ß = 115.080; p = 0.049) in women with FM. We found no association between serum CGRP levels and the variables measured (p ≥ 0.152). Our results suggest that VEGF may be related to pain processing in patients with FM.

Results From a Prospective, Clinical Study (US-nPower) Evaluating a Miniature Spinal Cord Stimulator for the Management of Chronic, Intractable Pain.

BACKGROUND: Chronic, intractable, neuropathic pain is readily treatable with spinal cord stimulation (SCS). Technological advancements, including device miniaturization, are advancing the field of neuromodulation. OBJECTIVES: We report here the results of an SCS clinical trial to treat chronic, low back and leg pain, with a micro-implantable pulse generator (micro-IPG). STUDY DESIGN: This was a single-arm, prospective, multicenter, postmarket, observational study. SETTING: Patients were recruited from 15 US-based comprehensive pain centers. METHODS: This open-label clinical trial was designed to evaluate the performance of the Nalu™ Neurostimulation System (Nalu Medical, Inc., Carlsbad, CA) in the treatment of low back and leg pain. Patients, who provided informed consent and were successfully screened for study entry, were implanted with temporary trial leads. Patients went on to receive a permanent implant of the leads and micro-IPG if they demonstrated a >= 50% reduction in pain during the temporary trial period. Patient-reported outcomes (PROs), such as pain scores, functional disability, mood, patient impression of change, comfort, therapy use profile, and device ease of use, were captured. RESULTS: At baseline, the average pain Visual Analog Scale (VAS) score was 72.1 ± 17.9 in the leg and 78.0 ± 15.4 in the low back. At 90 days following permanent implant (end of study), pain scores improved by 76% (VAS 18.5 ± 18.8) in the leg and 75% (VAS 19.7 ± 20.8) in the low back. Eighty-six percent  of both leg pain and low back pain patients demonstrated a >= 50% reduction in pain at 90 days following implant. The comfort of the external wearable (Therapy Disc and Adhesive Clip) was rated 1.16 ± 1.53, on average, at 90 days on an 11-point rating scale (0 = very comfortable, 10 = very uncomfortable). All PROs demonstrated statistically significant symptomatic improvement at 90 days following implant of the micro-IPG. LIMITATIONS:   Limitations of this study include the lack of long-term results (beyond 90 days) and a relatively small sample size of 35 patients who were part of the analysis; additionally, there was no control arm or randomization as this was a single-arm study, without a comparator, designed to document the efficacy and safety of the device. Therefore, no direct comparisons to other SCS systems were possible. CONCLUSIONS: This clinical study demonstrated profound leg and low back pain relief in terms of overall pain reduction, as well as the proportion of therapy responders. The study patients reported the wearable aspects of the system to be very comfortable.

Feldenkrais awareness though movement intervention for fibromyalgia syndrome: A proof-of-concept study.

INTRODUCTION: The Feldenkrais Method® is a form of awareness through movement (ATM) aimed at improving spatial and kinesthetic awareness through verbally guided movements, in order to learn more effective actions. METHOD: The present study, a proof-of-concept, observational, non-controlled prospective study, aims at exploring the effectiveness of ATM for fibromyalgia syndrome (FM), measuring the effect by means of multi-dimensional questionnaires, administered at baseline and after 4 months of ATM activity. RESULTS: One hundred twenty-eight FM patients (mean age 54 years old, 2% males) participated in the study. A statistically significant improvement was found in FM-specific measures (Polysymptomatic Distress Scale, PDS) (p = 0.003) and the Pain Catastrophization Scale (PCS) (p = 0.020); coherently, the Revised Fibromyalgia Impact Questionnaire (FIQR) showed a trend in improvement after the intervention, although this improvement was not statistically significant. The logistic regression analysis found a correlation between PDS, fatigue and anxiety measures; PCS, years from diagnosis and anxiety. CONCLUSION: ATM could improve FM-specific measures and pain-related catastrophizing. Further studies are needed to identify FM subgroups in order to find personalized targets that can be used to guide treatments.