Peak Pain Research Articles

Rebound pain following peripheral nerve block anaesthesia in acute ankle fracture surgery: An exploratory pilot study.

Peripheral nerve blocks (PNB) are increasingly used for anaesthesia and postoperative pain control in acute orthopaedic limb surgery but rebound pain upon cessation of PNBs may challenge the benefits on the pain profile. We aimed to explore the pain profile following acute ankle fracture surgery under PNB anaesthesia and investigate if rebound pain could pose a clinical problem. Exploratory, observational study of adults scheduled for acute primary internal fixation of an ankle fracture under ultrasound-guided popliteal sciatic and saphenous ropivacaine block anaesthesia. Postoperatively, patients regularly registered pain scores while receiving a fixed analgesics regimen and patient controlled morphine on-demand. We analysed morphine consumption and depicted the detailed pain profiles as graphs allowing for visual analysis of pain courses, including rebound pain. Secondly, we compared the area under the curve and peak pain between relevant age-subgroups. We included 21 patients aged 20-83. Depicted pain profiles reveal that PNB supplied effective and long lasting postoperative pain control, but cessation of the PNB led to intense rises in pain scores with six out of nine 20-60-year-olds reaching severe pain levels. The rebound was less pronounced in patients >60years old, but nearly all reached moderate pain levels. Morphine consumption rates were high during the rebound. This study thoroughly analyses the post-PNB pain profile and suggests rebound pain is a clinically relevant and problematic issue with the potential to outweigh the PNB benefits, especially for younger patients. The conclusions are tentative, and a randomised study is pending.

A longitudinal analysis of pain experience and recall in fibromyalgia

To evaluate pain experiences and memories in fibromyalgia (FM) patients over time. Participants included 572 females who were members of a large health maintenance organization who had a diagnosis of FM syndrome (FMS) and met inclusion criteria for the study. Recruitment was for an intervention study that tested the effects of social support and education treatment arms, but there were no treatment effects. Reports of experiential pain (EP), historical peak pain (HPP), and historical valley pain (HVP) for FM were collected. Differences between HPP and EP and EP and HVP (bias) were calculated to determine whether HPP and HVP were distributed evenly around EP over time across participants. Models were performed to assess personal history and psychosocial factors that affect EP, HPP, HVP, and bias. There was systematic tendency for HPP to be significantly larger than EP relative to EP vs HVP. EP and HPP decreased significantly over time, but not HVP. There were significant predictors of EP, HPP, HVP, and bias, including depression, self-efficacy, and sleep quality, among others. The experiences and recollections of pain in FM appear to provide a unique means of understanding the maintenance of chronic pain-including factors that affect this process.

High pain intensity after total shoulder arthroplasty

As reimbursement becomes increasingly tied to quality and patient experience, there is growing interest in alleviation of postoperative pain combined with optimal opioid stewardship. We characterized predictors of severe inpatient pain after elective total shoulder arthroplasty and evaluated its association with opioid use, operative time, hospital length of stay, discharge disposition, and cost. We identified 415 patients undergoing elective primary total shoulder arthroplasty between 2016 and 2017 from our registry. Severe postoperative pain was defined as peak pain intensity ≥75th percentile. Multivariable logistic regression modeling was used to determine preoperative characteristics associated with severe pain, including demographics, emotional health, comorbidities, and American Shoulder and Elbow Surgeons score. Opioid consumption was expressed as oral morphine equivalents (OMEs). Costs were calculated using time-driven activity-based costing. In decreasing order of magnitude, the predictors of severe postoperative pain were greater number of self-reported allergies, preoperative chronic opioid use, lower American Shoulder and Elbow Surgeons score, and depression. Patients reporting severe pain took more opioids (202 vs. 84 mg OMEs), stayed longer in the hospital (2.9 vs. 2.0 days), used postacute inpatient rehabilitation services more frequently (28% vs. 10%), and were more likely to be high-cost patients (23% vs. 5%; all P < .001), but they did not have longer operations (166 vs. 165 minutes, P = .86). Efforts to address psychological and social determinants of health might do as much or more than technical improvements to alleviate pain, limit opioid use, and contain costs after shoulder arthroplasty. These findings are important in the redesign of care pathways and bundling initiatives.

Initial Experiences With Robotic Single-Site Thoracic Surgery for Mediastinal Masses

The da Vinci Single-Site platform (Intuitive Surgical, Mountain View, CA) has been applied in many fields of surgery, but use of this single-site platform in thoracic surgery has not been reported. This study reported our experiences and surgical outcomes with robotic single-site surgery in the field of thoracic surgery. We retrospectively reviewed 14 patients who underwent robotic single-site thoracic surgery at 2 different institutions. All 14 cases were successfully completed, without conversion to conventional multiport robotic surgery. The most frequent diagnoses were thymic cyst (n= 4) and pericardial cyst (n= 3). The median largest mass size was 4.1 cm (range, 2.0 to 6.5 cm). The median operation time was 105 minutes (range, 27 to 185 minutes). After the operation, pleural effusion occurred in 1 patient (case 7) on the side on which the operation was performed but was managed with conservative treatment. The median duration of chest tube stay was 2 days (range, 1 to 3 days), and hospital stay was 4 days (range, 3 to 11 days). The median peak pain score after the operation was 3 (range, 1 to 7). Compared with thoracoscopic single-port surgery, robotic single-site thoracic surgery showed a longer operative time and higher cost. This study demonstrated that robotic single-site thoracic surgery for mediastinal masses is a safe and feasible procedure. Although this study reports the initial series and the cases were relatively simple, more advanced and complex procedures could be done with the advent of new technology in the near future.

Determination of ED50 and time to effectiveness for intrathecal hydromorphone in laboring patients using Dixon\u2019s up-and-down sequential allocation method

BackgroundWith the increasing occurrence of drug shortages, understanding the pharmacokinetics of alternative intrathecal opioid administration has gained importance. In particular, additional data are needed to comprehensively evaluate the analgesic properties of intrathecal hydromorphone in the laboring patient. In a phase 2 clinical trial, we set out to determine the median effective dose (ED50) and time to effectiveness for this drug in this population.MethodsUsing Dixon’s up-and-down sequential allocation method, twenty women presenting for labor analgesia were prospectively enrolled. A combined spinal-epidural technique was used to deliver the determined dose of intrathecal hydromorphone. Visual analog pain scores were obtained assessing peak pain scores during serial uterine contractions. Effective pain relief was defined as achieving a pain score of less than or equal to 3 out of 10. The dose was deemed to be ineffective if the patient failed to achieve this level of relief after 30 min.ResultsThe ED50 of hydromorphone in our population was 10.9 μg (95% confidence interval 5.6–16.2 μg). Amongst patients for whom the dose was effective, the median time to pain relief was 24 min. One patient experienced both nausea and pruritus. No other complications were noted.ConclusionDue to the prolonged time to onset, hydromorphone cannot be recommended in favor of substantively better alternatives such as sufentanil and fentanyl.Trial registrationClinicaltrials.gov registration number: NCT01598506.

Alterations in Temporal Summation of Pain and Conditioned Pain Modulation Across an Episode of Experimental Exercise-Induced Low Back Pain

Persistent pain conditions, including low back pain (LBP), are often accompanied by alterations in pronociceptive and antinociceptive mechanisms, as quantified by temporal summation of pain (TSP) and conditioned pain modulation (CPM). It remains unclear whether altered pain sensitivity, CPM, and/or TSP are a consequence of pain presence or determine the degree of pain development. Pressure pain sensitivity, TSP, and CPM were assessed across an episode of exercise-induced LBP maintained for several days. Thirty healthy individuals participated in 3 experimental sessions: before (day 0), 2 days after fatiguing back muscle exercise with exercise-induced LBP present (day 2), and after pain resolution (day 7). Both handheld and cuff pressure–pain thresholds, along with TSP (10-cuff pain stimuli at .5 Hz) and CPM (cuff pain detection threshold prior versus during painful pressure conditioning) were assessed, alongside questionnaires pertaining to pain, disability, mood, sleep, menstruation, physical activity, and catastrophizing. The exercise-induced LBP model produced mild pain and disability, and reductions in pressure pain thresholds over both the lumbar and distant testing sites (p < .007). No pain-related changes were observed for TSP (p > .44) or CPM (p > .17). The baseline TSP was associated with the peak pain intensity of the exercise-induced LBP (p < .003).Perspective: Pressure–pain sensitivity was impacted by the presence of exercise-induced LBP, whereas TSP seemed to be more stable and was instead associated with the intensity of pain developed. No significant pain-related changes or associations were observed for CPM, suggesting this measure may have less usefulness in mild musculoskeletal pain conditions.

The Effects of a Proximal Crush on Pain in a Rat Neuroma Model

Grant support received from: 2016 AFSH Basic Science Grant Other: Washington University, Checkpoint Surgical (M. Wood) A nerve crush induces an alternative growth program at the neuron level compared with the transection injury, which may modulate the development of pain. Our study evaluated the effect of performing a proximal nerve crush in a rat sciatic neuroma model to evaluate its efficacy as an adjunctive intervention for prevention and/or treatment of painful neuromas. The study consisted of 2 arms: (1) neuropathic pain prevention with a 2-week secondary intervention, and (2) neuropathic pain treatment with a 6-week secondary intervention. Male Lewis rats (n = 9) had an initial sciatic transection proximal to the trifurcation, followed by an intervention consisting of a sham surgery, proximal crush, or neuroma resection. The animals were tested weekly for pain-related behavior utilizing cold allodynia testing. Dorsal root ganglions were harvested at 5 months for both arms to assess pain-related gene expression profiles. Neuropathic pain prevention: Cold allodynia response slowly increased in all groups after the initial injury. Following the intervention to mitigate the development of cold allodynia responses, by day 56, the proximal crush group had a cold allodynia time of 3.6 ± 3.5 (mean ± standard deviation, seconds), which was significantly lower than the neuroma resection group, 17.6 ± 13.1 P < .01. Neuropathic pain treatment: Cold allodynia response was allowed to plateau following the initial sciatic transection, to a maximum of 22.6 ± 6.8. Following crush intervention, cold allodynia was only 9.5 ± 7.8 by week 8, 17.7 ± 7.6 in the resection group, and 17.1 ± 8.3 in the sham surgery group. These differences were not significant. Pain-related gene expression analysis is ongoing. •A proximal crush intervention modulates pain-related behavior in this rodent sciatic neuroma model when performed early.•Intervention after the development of peak pain (late intervention) was not effective in modulating pain behavior.•This study suggests a potential benefit of a proximal nerve crush as an adjunctive procedure when performed early, at the time of nerve transection or amputation. This research was supported by a Basic Science Grant from the American Foundation for Surgery of the Hand.

Offset analgesia is not affected by cold pressor induced analgesia.

Background and aims Offset analgesia (OA) is a pain modulating mechanism described as a disproportionately large decrease in pain intensity evoked by a minor decrease in stimulus intensity. Precise mechanisms of OA are still not elucidated and studies are needed to evaluate factors modulating OA. The aim of this study was to investigate OA before and during tonic cold pain (thought to induce descending inhibition), in a group of healthy volunteers. Methods A randomized, crossover study was performed in 17 healthy participants (8 males and 9 females). The OA paradigm lasted 35 s and was induced by the traditional method using thermal stimulation applied to the forearm. A constant control heat stimulus (CTL) paradigm was used as control to assess adaptation. Pain intensity was assessed continuously. For induction of tonic cold pain, the participants immersed their hand into 2°C water for 2 min. After 1 min and 25 s, the heat stimulation (OA or CTL paradigm) was repeated to assess the modulatory effect of the cold pressor test. Results It was possible to induce OA both before and during the cold pressor test. Tonic cold pain modulated the peak pain reported during both the OA (p=0.015) and CTL paradigms (p=0.001) reflecting endogenous pain modulation. However, the magnitude of OA was not modulated by tonic cold pain (p>0.05). Conclusions The offset analgesia magnitude was not modulated by simultaneously tonic cold pain, thought to reflect another endogenous pain modulation mechanism. Implications Neither offset analgesia magnitude nor adaptation were modulated by cold pressor induced endogenous analgesia. This could be explained by the fact, that offset analgesia was already at maximum in healthy participants. Hence, offset analgesia may not be a suitable assessment tool to investigate modulation induced by experimental methods or pharmacology in healthy participants.

Focal cryoballoon versus radiofrequency ablation of dysplastic Barrett’s esophagus: impact on treatment response and postprocedural pain

Radiofrequency ablation (RFA) is safe and effective for eradicating Barrett's esophagus (BE) but is associated with significant postprocedural pain. Alternatively, balloon-based focal cryoablation (CRYO) has recently been developed, which preserves the extracellular matrix and might therefore be less painful. Although data for CRYO are still limited, uncontrolled studies suggest comparable safety and efficacy to RFA in eradicating limited BE areas. Therefore, secondary endpoints such as pain might become decisive for treatment selection. We aimed to compare efficacy and tolerability between focal CRYO and RFA. We identified BE patients undergoing focal ablation (either RFA or CRYO) of all visible BE from our prospective cohort in 2 Dutch referral centers. After ablation, patients completed a 14-day digital diary to assess chest pain (0-10), dysphagia (0-4), and analgesics use. A follow-up endoscopy was scheduled after 3 months to assess the BE surface regression (blindly scored by 2 independent BE expert endoscopists). Outcomes were BE surface regression; 14-day cumulative scores (area under the curves [AUCs]) for pain, dysphagia, analgesics, and peak pain. We identified 46 patients (20 CRYO, 26 RFA) with similar baseline characteristics. The BE regression was comparable (88% vs 90%, P= .62). AUCs for pain, dysphagia, and analgesics were significantly smaller after CRYO versus RFA (all P< .01). Peak pain was lower after CRYO (visual analog scale 2 vs 4, P< .01), and the duration of pain was also shorter after CRYO (2 vs 4 days, P< .01). CRYO patients used analgesics for 2 days versus 4 days for RFA (P< .01). In this multicenter, nonrandomized cohort study, we found no differences in efficacy after a single treatment with CRYO and RFA for short-segment BE. Patients reported less pain after CRYO as compared with RFA. Moreover, CRYO patients used fewer analgesics. Our results suggest a different pain course favoring CRYO over RFA, but a randomized trial is needed for definitive conclusions. (Clinical trial registration number: NCT02249975.).

Benefits of intradialytic physiotherapy in quality of life, pain, edema and respiratory function of patients with chronic kidney disease

Abstract Introduction: Patients with chronic kidney disease suffer from a decline in quality of life and respiratory function, for various reasons related to this condition. Objective: To verify the influence of intradialytic physiotherapy on the quality of life and respiratory function in chronic renal patients. Methods: The sample was non-probabilistic and consisted of 51 individuals, of both sexes, aged between 30 and 60 years. The WHOQOL-Bref, an evaluation form, the Manovacuometer and Peak Flow were used to detect the impact of the physiotherapeutic intervention before and after an eight-week treatment protocol. Results: There was a difference in the comparison of the general QOL before and after (p = 0.006) the intervention, as well as in the improvement of the maximal forced expiratory flow peak (p = 0.001), the PEmax (p = 0.000), peak forced expiratory flow rate (0.017) and pain (p = 0.006). There was also improvement of edema (p = 0.013) and cramps (p = 0.000). Conclusion: The benefits of intradialytic physiotherapy in improving QOL and respiratory function in chronic kidney patients are explicit.

Diurnal variation in orthodontic pain: Clinical implications and pharmacological management

Pain is a bio-physiological phenomenon characterized by a circadian rhythm. A better understanding of diurnal variability in orthodontic pain perception would not only enhance our knowledge about how orthodontic pain intensity fluctuates over the 24-h day, but it also has a great potential to improve the clinical management of orthodontic pain. Since the administration timing of pharmacological interventions has a direct influence on their effectiveness, a sound knowledge of the timing of peak pain intensity would allow clinicians to better coordinate the administration timing of analgesics. The objective of this study was to explore and quantify the diurnal variation in orthodontic pain over a period of seven days following initial arch wires placement. A multilevel linear spline model was used for secondary data analysis. Data were obtained from an earlier published high quality randomized controlled trial involving 85 participants (42 males and 43 females; mean age 14.1years and SD 2.0). Results showed a significant diurnal variability in pain intensity during the first two days of force application for both sexes. However, females showed significantly greater diurnal variation in the pain than males. Clinical and research implications of observed diurnal variability in orthodontic pain perception are discussed.

Comparison of the Prophylactic Effect Between Acupuncture and Acupressure on Menstrual Migraine: Results of a Pilot Study

ObjectivesTo compare between acupuncture and acupressure for preventing menstrual migraine (MM). MethodsMM is one kind of migraine associated with menses in female. It is often associated with increased menstrual distress and disability, leading to decreased daily activity and quality of life. A randomized and controlled pilot study was conducted with three groups: verum acupuncture (VA) group, acupressure (AP) group, and control acupuncture (CA) group. The study lasted for 7 cycle-months, with a 1 cycle-month baseline observation (T1), a 3 cycle-month intervention (3 times per cycle-month) (T2–T4), and a 3 cycle-month follow-up (T5–T7). Outcome measures were number of migraine days, average and peak pain, total duration period of MM, and percentage of patients with ≥50% reduction in the number of MM days. ResultsA total of 18 participants were included in the analysis (VA, n = 7; AP, n = 6; CA, n = 5). Both VA and AP were significantly more effective than CA for reducing MM days during the intervention period. Both VA and AP tended to be more effective than CA for reducing peak pain during the intervention period. No significant differences for the outcomes were observed among VA, AP, and CA during the follow-up period. No serious adverse events were reported. DiscussionResults of the pilot study suggest that both VA and AP could be considered as alternative and safe prophylactic interventions for MM. Register ClinicalTrials.gov Identifier: NCT02592681.

Trainability of functional deficits in adults with scoliosis.

Scoliosis is an understudied diagnosis of a lateral spinal curvature, and is classified with a diagnostic feature of a curve exceeding 10 degrees. Most commonly, there is no known cause and the onset occurs in adolescence. Our laboratory has previously reported on baseline functional data in adults with Adolescent Idiopathic Scoliosis (AIS). The purpose of this follow-up study is to determine the change over time in patients who were treated for scoliosis in an out-patient orthopedic physical therapy clinic. Fourteen patients were treated for an average of 6.75 weeks, resulting in 12 treatments. Patients were assessed for improvements in lumbar strength, rotational strength/symmetry, pain, and functional index (Oswestry questionnaire). Strength and range of motion (ROM) of the trunk were measured and treated on MedX spinal dynamometers. During initial evaluation, 70.4% of the patients expressed spinal pain. Typical pain improved in 72.7% of patients; peak pain was improved in 50% of patients. The perceived functional index demonstrated that 58.3% of patients reported improved function. Initially, patients’ trunk rotation strength was reported at 28.3% below average. Following therapy, patients’ rotation strength improved on the left by 26.7% and 36.4% on the right, bringing strength closer to established norms while improving bilateral strength balance (i.e., reducing strength asymmetry). We conclude that adults with AIS may benefit from specific trunk strengthening interventions that improve strength, strength symmetry, pain, and self-perceived disability.

Effects of patient participation in the management of daily nursing goals on function recovery and resilience in surgical patients

To examine the effects of active patient participation in the management of daily nursing goal on surgical patient recovery. Nursing processes involving patient participation enable nursing interventions solely based on individual needs and expectations. This permits the establishment of nurse-patient treatment goals and supports permanent and effective nursing interventions through evaluation activities. A quasi-experiment that relies on a nonequivalent pretest-post-test design for the control group. A nursing intervention involving patient participation was applied to patients who underwent digestive cancer surgery in a surgical ward in the Republic of Korea. A daily goals sheet for patient participation was developed. Twenty-nine patients in the experimental group received the intervention every day from postoperative days 1-7 through the daily goals sheet. Data were collected on recovery in mobility, recovery of bowel movements, peak expiratory flow rate and pain and resilience after the experimental intervention. The control group contained 27 patients who were provided with routine nursing care alone. The daily nursing goal management group showed more rapid recovery in bowel movement, higher peak expiratory flow rate and lower pain scores than the control group. The daily nursing goal management group also had significantly higher resilience than the control group. Daily nursing goal management is an effective nursing intervention for improving function recovery and resilience in surgical patients. Patient participation in daily nursing goal management is an effective nursing intervention applicable to nurse-patient treatment goals and supports permanent and effective nursing interventions through evaluation activities.

Pain experience in adults undergoing treatment: A longitudinal evaluation.

To quantify the intensity and duration of pain experience in adults over the initial three visits of fixed appliance-based orthodontic treatment. A secondary objective was to assess the relationship between pain experience and analgesic use, dental irregularity, gender, and age. A prospective longitudinal study design was adopted. Fifty-eight adults undergoing fixed appliance treatment in five orthodontic practices recorded pain experience at four time points (4 hours, 24 hours, 3 days, and 7 days) following the initial bond-up appointment (T0) and first (T1) and second (T2) routine follow-up adjustment appointments using a visual analogue scale. In addition, subjects recorded the dosage and frequency of analgesic use. A slightly greater proportion of women (57%) were recruited, with a mean sample age of 34.69 (SD 12.11) years. Peak pain was experienced between 24 hours and 3 days following appliance placement (T0) and subsequent adjustments (T1 and T2). The highest mean pain score arose at T0 followed by T2 and T1 adjustments, with the difference between pain levels at these appointment intervals being statistically significant ( P < .001). The use of analgesics following each appointment mirrored pain experience, with pain score, appointment, and time point all being significant predictors of analgesic consumption. The level of dental irregularity, gender, or age did not predict pain levels reported. Adults undergoing fixed orthodontic therapy should be advised that they are most likely to experience increased levels of pain for 1 to 3 days following placement of their appliance and subsequent adjustment visits.

Combined effects of knee brace, laterally wedged insoles and toe-in gait on knee adduction moment and balance in moderate medial knee osteoarthritis patients

ObjectiveTo test the hypothesis that toe-in gait (TI) will further reduce first peak (Knee Adduction Moment) KAM and decrease balance when combined with a knee brace (KB) and laterally wedged insoles (LWI) in medial knee osteoarthritis (kOA) patients. ParticipantsTwenty patients with bilateral symptomatic medial kOA. Interventions4-point leverage-based KB, full-length LWI with 5° inclination and toe-in gait (TI). Main outcome measuresFirst and second peak knee adduction moment (fKAM and sKAM respectively), balance and pain. MethodsThe fKAM and sKAM were determined from 3-dimensional gait analysis with six randomized conditions: (1) N (without any intervention), (2) KB, (3) KB + TI, (4) LWI, (5) LWI + TI, (6) KB + LWI + TI. Balance was assessed by Biodex Balance System using three stability settings, (i) Static (ii) Moderate dynamic setting for fall risk (FR12) and (iii) High dynamic setting for fall risk (FR8). ResultsThe reduction in fKAM and sKAM was greatest (19.75% and 12%) when TI was combined with KB and LWI respectively. No change in balance was observed when TI combined with KB, and LWI and when used concurrently with both the orthosis at static and FR12 conditions. Significant balance reduction was found at FR8 for KB + TI (22.22%), and KB + LWI + TI (35.71%). Pain increased significantly for KB (258%), KB + TI (305%), LWI + TI (210%) and KB + LWI + TI (316%). LWI showed no effect on pain. ConclusionsThere is a synergistic effect of TI when combined with KB and LWI concurrently in sKAM reduction. However, the concurrent use of TI, KB and LWI decreases balance and pain as assessed on a highly dynamic platform.

Influence of Obstructive Sleep Apnea in the Functional Aspects of Patients With Osteoarthritis.

It has been demonstrated in recent studies that obstructive sleep apnea (OSA) is the most prevalent sleep disorder in patients with osteoarthritis (OA), and thus the current study aimed to investigate the influence of OSA on knee extensor torque, pain, stiffness, and physical function in men with low-grade knee OA. The study included 60 male volunteers, aged 40 to 70 years, allocated into four groups: Group 1 (G1) Control (n = 15): without OA and without OSA; Group 2 (G2) (n = 15): with OA and without OSA; Group 3 (G3) (n = 15): without OA and with OSA; and Group 4 (G4) (n = 15) with OA and with OSA. All volunteers were examined using knee radiographs and polysomnography, responded to the Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire, and completed a test on an isokinetic dynamometer to evaluate peak isometric knee extensor torque, both concentric and eccentric (90°/s and 180°/s). Regarding the data from the WOMAC questionnaire (for pain, stiffness, and physical function), it was observed that G4 showed higher values compared to G1 or G3. For the concentric isometric and isokinetic peak knee extensor torque, lower values were observed in G4 compared to G1 or G3. Patients who have knee OA in the early grades, when associated with OSA, have higher changes of the peak extensor torque, pain, stiffness, and physical function, compared with patients who did not have OSA. Registry: ClinicalTrials.gov, Identifier: NCT01422967, Title: Changes Of Sleep on the Sensoriomotor and Cytokine In Patients With Osteoarthritis, URL: https://clinicaltrials.gov/ct2/show/NCT01422967.

(203) - Within session reliability of conditioned pain modulation in young healthy adults depends on location of test stimulus

The aim of this repeatability study was to investigate the between and within session reliability of conditioned pain modulation (CPM) in young healthy individuals. Thirty subjects (19.3 ± 1.5 years; 15 females) participated in two randomized sessions separated by approximately one week. During each session, pressure pain thresholds (PPTs) at the right quadriceps and upper trapezius muscles were assessed before and during ice water immersion (left foot, 0 ± 1°C, 105 ± 18 seconds). In one of the sessions, the CPM protocol was repeated following 23 minute quiet rest. Percentage change in CPM within and between sessions at each assessment site were compared with repeated measures ANOVAs. Intraclass correlations (ICCs (3,k)) with 95% confidence interval (CI) as a measure of relative reliability were computed within and between sessions for each assessment site. During submersion of foot in the ice water bath, participants reported moderate-to-severe peak pain intensity (6.6 ± 1.8 using 0/10 Numerical Rating Scale). Peak pain intensity decreased significantly between sessions (7.0 ± 1.0 to 6.4 ± 1.7; P = .01) but was similar within session (P > .05). PPTs significantly increased during cold pressor tests compared to baseline without ice (P < .001). The CPM response decreased at the quadriceps and upper trapezius muscles similarly following quiet rest compared with before quiet rest (trial: P < .05; trial x site: P > .05). Despite the decrease, CPM had a fair-to-good within session reliability; although this differed based on the location of the test stimulus (ICCs: quadriceps = .707 [.395–.859]; upper trapezius = .433 [−.190–.730]). Between-session reliability was poor at both assessment sites (ICCs: quadriceps = .208 [−.715–.628]; upper trapezius = .350 [−.401–.694]). These results suggest that CPM is not fully restored following a 23-minute washout period and reliability of CPM may change depending on location of the test stimulus. Future studies are needed to investigate the factors involved in CPM reliability.

Knee extensor strength gains mediate symptom improvement in knee osteoarthritis: secondary analysis of a randomised controlled trial

To determine if an increase in knee extensor strength mediates the effect of a 12-week knee extensor strength training program on pain and physical function improvement in people with knee osteoarthritis (OA). Secondary analysis from a randomised controlled trial comparing the effects of a 12-week knee extensor strengthening exercise program to a control group with no intervention. Data from participants with complete data (n=97) enrolled in a previous clinical trial were analysed. Baseline and 12-week follow-up assessments included peak isometric knee extensor strength, pain and physical function. Peak knee extensor strength (Nm/kg) was assessed on an isokinetic dynamometer and subscales of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index were used to assess pain and physical function. Twelve-week change in pain and physical function were regressed separately, on 12-week change in knee extensor strength and group allocation. Covariates included baseline pain or physical function as appropriate, and baseline knee extensor strength, age, sex and knee alignment (stratification variable). Improved knee extensor strength mediated the effect of the strengthening program on both pain relief (mediated effect size=0.69, 95% confidence intervals (CI) 0.05-1.33, P=0.03), and improved physical function (mediated effect size=1.86, 95% CI 0.08-3.64, P=0.04), at 12 weeks. Increased knee extensor strength partially mediates the effect of a knee extensor strength training program on pain and physical function improvement in people with knee OA.

Development and Evaluation of Floating Pulsatile Drug Delivery System Using Meloxicam

Objective: The objective of this research work was to develop and evaluate the floating– pulsatile drug delivery system (FPDDS) of meloxicam intended for Chrono pharmacotherapy of rheumatoid arthritis. Methods: The system consisting of drug containing core, coated with hydrophilic erodible polymer, which is responsible for a lag phase for pulsatile release, top cover buoyant layer was prepared with HPMC K4M and sodium bicarbonate, provides buoyancy to increase retention of the oral dosage form in the stomach. Meloxicam is a COX-2 inhibitor used to treat joint diseases such as osteoarthritis and rheumatoid arthritis. For rheumatoid arthritis Chrono pharmacotherapy has been recommended to ensure that the highest blood levels of the drug coincide with peak pain and stiffness. Result and discussion: The prepared tablets were characterized and found to exhibit satisfactory physico-chemical characteristics. Hence, the main objective of present work is to formulate FPDDS of meloxicam in order to achieve drug release after pre-determined lag phase. Developed formulations were evaluated for in vitro drug release studies, water uptake and erosion studies, floating behaviour and in vivo radiology studies. Results showed that a certain lag time before drug release which was due to the erosion of the hydrophilic erodible polymer. The lag time clearly depends on the type and amount of hydrophilic polymer which was applied on the inner cores. Floating time and floating lag time was controlled by quantity and composition of buoyant layer. In vivo radiology studies point out the capability of the system of longer residence time of the tablets in the gastric region and releasing the drug after a programmed lag time. Conclusion: The optimized formulation of the developed system provided a lag phase while showing the gastroretension followed by pulsatile drug release that would be beneficial for chronotherapy of rheumatoid arthritis and osteoarthritis.