The autonomic and nociceptive response to acute experimental stress is impaired in people with knee osteoarthritis: A preliminary study.

Objective: Alterations in autonomic function are evident in some chronic pain conditions but have not been thoroughly examined in people with osteoarthritis (OA). The study aimed to examine resting autonomic nervous system (ANS) function in people with knee OA, and the response of the autonomic and nociceptive systems to acute stress. Methods: A preliminary cross-sectional study was undertaken involving people with knee OA (n = 14), fibromyalgia (n = 13), and pain-free controls (n = 15). The sympathetic and parasympathetic components of the ANS were assessed through measures of pre-ejection period (PEP), skin conductance level (SCL), and high frequency heart rate variability (HF HRV). The nociceptive system was assessed through pain ratings associated with a tonic heat pain stimulus. In separate sessions, ANS and heat pain measures were assessed at rest and in response to nociceptive and mental arithmetic stressors. Results: The knee OA group showed reduced HF HRV at rest and reduced modulation in response to stress. Resting PEP and SCL were normal in the knee OA group but PEP modulation was impaired in both chronic pain groups during nociceptive stress. The expected reduction in tonic heat pain ratings in response to stress was lacking in the knee OA and FM groups. Conclusion: Preliminary evidence shows impaired parasympathetic nervous system function at rest and in response to nociceptive and mental stress in people with knee OA, with some evidence of altered sympathetic nervous system function. Impaired ANS function could contribute to ongoing pain experienced, and interventions that target ANS function could be beneficial.

The incidence, impact, and risk factors for moderate to severe persistent pain after breast cancer surgery: a prospective cohort study.

BACKGROUND: Few Australasian studies have evaluated persistent pain after breast cancer surgery. OBJECTIVE: To evaluate the incidence, impact, and risk factors of moderate to severe persistent pain after breast cancer surgery in a New Zealand cohort. DESIGN: Prospective cohort study. METHODS: Consented patients were reviewed at 3 timepoints (preoperative, 2 weeks and 6 months postoperative). Pain incidence and interference, psychological distress and upper limb disability were assessed perioperatively. Clinical, demographic, psychological, cancer treatment-related variables, quantitative sensory testing, and patient genotype (COMT, OPRM1, GCH1, ESR1, and KCNJ6) were assessed as risk factors using multiple logistic regression. RESULTS: Of the 173 patients recruited, 140 completed the 6-month follow-up. Overall, 15.0% (n = 21, 95% CI: 9.5%-22.0%) of patients reported moderate to severe persistent pain after breast cancer surgery with 42.9% (n = 9, 95% CI: 21.9%-66.0%) reporting likely neuropathic pain. Pain interference, upper limb dysfunction and psychological distress were significantly higher in patients with moderate to severe pain (P < .004). Moderate to severe preoperative pain (OR= 3.60, 95% CI: 1.13-11.44, P = .03), COMT rs6269 GA genotype (OR = 5.03, 95% CI: 1.49-17.04, P = .009) and psychological distress at postoperative day 14 (OR= 1.08, 95% CI: 1.02-1.16, P = .02) were identified as risk factors. Total intravenous anesthesia (OR= 0.31, 95% CI: 0.10 - 0.99, P = .048) was identified as protective. CONCLUSION: The incidence of moderate to severe persistent pain after breast cancer surgery is high with associated pain interference, physical disability, and psychological distress. Important modifiable risk factors were identified to reduce this important condition.

Trajectories of Pain and Function Outcomes up to 5 to 8 Years Following Total Knee Arthroplasty.

BACKGROUND: There appears to be substantial variability in outcomes > 2 years following total knee arthroplasty (TKA) that is masked by whole group analyses. The goal of the study was to identify trajectories of pain and function outcomes up to 5 to 8 years post-TKA and to identify baseline factors that are associated with different trajectories of recovery. METHODS: Baseline, 6-month, and 12-month pain and function data were collected in a previous study investigating predictors of outcome following primary TKA (n = 286), along with a variety of baseline predictor variables. The present study obtained pain and function data at 5 to 8 years following TKA in the same cohort (n = 201). Latent class linear mixed models were used to identify different classes of pain and functional trajectories over time. The extent to which differences across latent classes were explained by baseline predictor variables was determined. RESULTS: Three classes of pain and two classes of function trajectory were identified. While most patients (84% to 93%) followed a trajectory that showed an initial rapid gain following surgery that was sustained through 5 to 8 years, both pain and function included at least one trajectory class that showed a meaningful change after 12 months. No predictor variables were significantly associated with either the pain or function classes. CONCLUSIONS: Most patients follow a traditional trajectory of recovery in knee pain and function over 5 to 8 years. However, alternative trajectories are observed in an important minority of patients such that knee pain and function at 12 months after surgery does not always reflect outcomes at 5 to 8 years.

The autonomic and nociceptive response to acute exercise is impaired in people with knee osteoarthritis.

Objectives: An acute bout of exercise typically leads to short term exercise induced hypoalgesia (EIH), but this response is more variable in many chronic pain populations, including knee osteoarthritis (OA) and fibromyalgia (FM). There is evidence of autonomic nervous system (ANS) dysfunction in some chronic pain populations that may contribute to impaired EIH, but this has not been investigated in people with knee OA. The aim of this study was to assess the acute effects of isometric exercise on the nociceptive and autonomic nervous systems in people with knee OA and FM, compared to pain-free controls. Methods: A cross-sectional study was undertaken with 14 people with knee OA, 13 people with FM, and 15 pain free controls. Across two experimental sessions, baseline recordings and the response of the nociceptive and autonomic nervous systems to a 5-min submaximal isometric contraction of the quadriceps muscle was assessed. The nociceptive system was assessed using pressure pain thresholds at the knee and forearm. The ANS was assessed using high frequency heart rate variability, cardiac pre-ejection period, and electrodermal activity. Outcome measures were obtained before and during (ANS) or immediately after (nociceptive) the acute bout of exercise. Results: Submaximal isometric exercise led to EIH in the control group. EIH was absent in both chronic pain groups. Both chronic pain groups showed lower vagal activity at rest. Furthermore, people with knee OA demonstrated reduced vagal withdrawal in response to acute isometric exercise compared to controls. Sympathetic reactivity was similar across groups. Discussion: The findings of reduced tonic vagal activity and reduced autonomic modulation in response to isometric exercise raise the potential of a blunted ability to adapt to acute exercise stress and modulate nociception in people with knee OA. The impairment of EIH in knee OA may, in part, be due to ANS dysfunction.

A combination of high preoperative pain and low radiological grade of arthritis is associated with a greater intensity of persistent pain 12 months after total knee arthroplasty.

AIMS: Despite new technologies for total knee arthroplasty (TKA), approximately 20% of patients are dissatisfied. A major reason for dissatisfaction and revision surgery after TKA is persistent pain. The radiological grade of osteoarthritis (OA) preoperatively has been investigated as a predictor of the outcome after TKA, with conflicting results. The aim of this study was to determine if there is a difference in the intensity of pain 12 months after TKA in relation to the preoperative radiological grade of OA alone, and the combination of the intensity of preoperative pain and radiological grade of OA. METHODS: The preoperative data of 300 patients who underwent primary TKA were collected, including clinical information (age, sex, preoperative pain), psychological variables (depression, anxiety, pain catastrophizing, anticipated pain), and quantitative sensory testing (temporal summation, pressure pain thresholds, conditioned pain modulation). The preoperative radiological severity of OA was graded according to the Kellgren-Lawrence (KL) classification. Persistent pain in the knee was recorded 12 months postoperatively. Generalized linear models explored differences in postoperative pain according to the KL grade, and combined preoperative pain and KL grade. Relative risk models explored which preoperative variables were associated with the high preoperative pain/low KL grade group. RESULTS: Pain 12 months after TKA was not associated with the preoperative KL grade alone. Significantly increased pain 12 months after TKA was found in patients with a combination of high preoperative pain and a low KL grade (p = 0.012). Patients in this group were significantly more likely to be male, younger, and have higher preoperative pain catastrophizing, higher depression, and lower anxiety (all p ≤ 0.05). CONCLUSION: Combined high preoperative pain and low radiological grade of OA, but not the radiological grade alone, was associated with a higher intensity of pain 12 months after primary TKA. This group may have a more complex cause of pain that requires additional psychological interventions in order to optimize the outcome of TKA.Cite this article: Bone Joint J 2022;104-B(11):1202-1208.

Neuropathic Pain in Hand Osteoarthritis: A Cross-Sectional Study.

Symptomatic hand osteoarthritis (OA) is a severely debilitating condition. Neuropathic pain (NP) has been shown to be a factor affecting pain severity, hand function, psychological wellbeing, body schema, and the number of pain medications in people with OA of other joints. The aim of this study was to assess the prevalence of NP in symptomatic hand OA and assess its association with pain, hand function, measures of psychological wellbeing, sleep, body schema disturbances, and number of pain medications. Participants with symptomatic hand OA diagnosed through the American College of Rheumatology criteria, were recruited and completed a series of online questionnaires. These included the Douleur Neuropathique 4 interview (DN4-interview), Short Form Brief Pain Inventory (SF-BPI), Neglect-like Symptoms questionnaire, Functional Index of Hand Osteoarthritis (FIHOA), Centre for Epidemiologic Studies Depression Scale (CES-D), Pain Catastrophising Scale (PCS), and the Pittsburgh Sleep Quality Index (PSQI). Logistic regression with age, body mass index, and sex as covariates were utilised to assess differences between participants with and without NP as identified through the DN4-interview. Correlation analysis assessed the relationship between pain intensity, body schema alterations, and number of pain medications. A total of 121 participants were included in the present study. Forty-two percent of participants presented with NP. Participants with NP reported higher levels of worst pain (OR: 10.2 95% CI: 2.2 to 48.5; p = 0.007). Worst pain intensity correlated with the number of pain medications (rho = 0.2; p = 0.04), and neglect-like symptoms (rho = 0.4; p < 0.0001). No difference between phenotypes was shown for catastrophising, function, depression, neglect-like symptoms, pain interference, or sleep. A large proportion of people with symptomatic hand OA present with NP. This phenotype is characterised by greater levels of pain intensity. Pain intensity is associated with number of pain relief medications and body schema alteration. Psychological factors, hand function, and sleep do not appear to be affected by the presence of NP.

Experimental Hand and Knee Pain Cause Differential Effects on Corticomotor Excitability.

Acute pain elicits a well-known inhibitory effect on upper limb corticomotor excitability, whereas the temporal effects of lower-limb experimental pain and pain in a remote limb are less clear. The aim of this study was to compare the temporal corticomotor excitability changes in the upper and lower limbs in response to acute upper and lower limb pain. In a cross-over design, 13 participants (age 29 ± 9 years; 12 male) attended 2 sessions where experimental pain was induced by injecting hypertonic saline into either the first dorsal interosseous (FDI) muscle or infrapatellar fat pad at the knee, inducing a short-lasting pain experience scored on a numerical rating scale (NRS). Motor evoked potentials (MEPs) in response to transcranial magnetic stimulation were recorded in the FDI and vastus lateralis (VL) muscles before, during, and following pain. Hand and knee pain NRS scores were not significantly different. Hand pain elicited a short duration inhibition of the FDI MEPs (P < .0001) together with a facilitation of VL MEPs (P = .001) that outlasted the duration of pain. Knee pain elicited a short-duration facilitation of VL MEPs (P = .003) with no significant effect in the FDI MEPs (P = .46). The findings indicate a limb-specific corticomotor response to experimental pain that may be related to limb function. PERSPECTIVE: These data demonstrate the impact of acute, experimental pain on corticomotor excitability in the upper and lower limbs. This facilitates our understanding of the effect of pain on motor control of both local and distant muscles.

A Higher Grey Matter Density in the Amygdala and Midbrain Is Associated with Persistent Pain Following Total Knee Arthroplasty.

OBJECTIVE: The development of persistent pain following total knee arthroplasty (TKA) is common, but its underlying mechanisms are unknown. The goal of the study was to assess brain grey matter structure and its correlation with function of the nociceptive system in people with good and poor outcomes following TKA. SUBJECTS: Thirty-one people with LOW_PAIN (<3/10 on the numerical ratings scale [NRS]) at six months following TKA and 15 people with HIGH_PAIN (≥3/10 on the NRS) were recruited into the study. METHODS: Grey matter in key brain areas related to nociception was analyzed using voxel-based morphometry (VBM). Nociceptive facilitatory and inhibitory processes were evaluated using quantitative sensory testing (QST). QST scores and grey matter density in prespecified brain regions were compared between the LOW_PAIN and HIGH_PAIN groups. Regression analyses were used to analyze the associations between the grey matter and QST scores. RESULTS: There were no between-group differences in QST measures. In the VBM analysis, the HIGH_PAIN group had a higher grey matter density in the right amygdala, right nucleus accumbens, and in the periaqueductal grey (PAG), but lower grey matter density in the dorsal part of the left caudate nucleus. Grey matter density in the right amygdala and PAG correlated positively with temporal summation of pain. CONCLUSIONS: Persistent pain at six months after TKA is associated with a higher grey matter density in the regions involved in central sensitization and pain-related fear, which may contribute to the development of persistent pain after surgery.

Stretch reflex changes in ACL-deficient individuals and healthy controls during normal and surprise landings.

No studies in ACL-D individuals have examined neuromuscular adaptations during landing from a jump where an unexpected mechanical event changes the pre-programmed course of movement. The purpose of this study was to compare pre- and post-landing muscle activation in ACL-D individuals and uninjured controls during normal and surprise landings. Nineteen ACL-D and 17 uninjured volunteered. Participants performed repeated single leg landings from 30 and 15 cm heights. During 15 cm landings, a single surprise landing was performed where participants unexpectedly fell through a false surface at 15 cm to the solid floor a further 15 cm below. Electromyography (EMG) amplitude from vastus lateralis (VL), lateral hamstrings (LH), and soleus (Sol) was recorded. Pre-landing (-60 to 0 ms), post-landing short latency (31-60 ms), and post-landing medium latency (61-90 ms) periods were examined. Comparisons in EMG amplitudes were made across limbs (ACL-D, ACL intact, and control) in 30 cm landings. Additionally, the ratio of EMG amplitude in surprise:30 cm normal landings was analyzed. Post-landing LH EMG was reduced in the ACL-D compared to control limbs at short latencies (P < 0.05). Post-landing VL EMG was reduced in the ACL-D and ACL intact compared to the control limb at both latencies (P < 0.05). Surprise landings notably increased post-landing EMG in all muscles, across all limbs (P < 0.001). However, the gain in VL EMG was significantly greater in ACL-D and ACL intact limbs (P < 0.05). These changes in neuromuscular control of ACL-D individuals during expected and surprise landings may have important implications for rehabilitation, instability, and the risk of secondary injury.

Experimental knee pain impairs joint torque and rate of force development in isometric and isokinetic muscle activation.

PURPOSE: To investigate the effects of acute experimental knee joint pain on maximum force generation and rate of force development (RFD) of the quadriceps muscle during isometric and dynamic muscle activations. METHODS: The right knee of 20 healthy people was injected with hypertonic saline to create an acute pain experience. Measurements of maximum knee extensor torque during isometric, concentric, and eccentric contractions were undertaken using a Biodex dynamometer. The RFD was also examined during the isometric contractions. Quadriceps muscle activity was obtained using electromyography (EMG). The outcome measures were obtained at baseline, during pain, and after knee pain had resolved. RESULTS: Maximum joint torque and peak EMG were significantly reduced during pain, but there were no differences across the three types of contraction. The maximum RFD and rate of EMG rise were also reduced during pain, primarily at 50-100 ms post-contraction onset. The RFD and EMG rise were largely unaffected at later time periods following contraction onset (150-200 ms). CONCLUSIONS: Acute joint pain has a similar impact on isometric and isokinetic contractions despite differences in neural control strategies. Joint pain also impairs rapid muscle activation and the RFD. These findings are important for people with musculoskeletal pain as it likely contributes to impairments in joint function in these populations.

The Prevalence, Impact, and Risk Factors for Persistent Pain After Breast Cancer Surgery in a New Zealand Population.

OBJECTIVE: Few Australasian studies have assessed persistent pain after breast cancer surgery. This study aims to evaluate the prevalence, impact, and risk factors of moderate to severe persistent pain after breast cancer surgery in a New Zealand population. METHODS: Retrospective cross-sectional study of patients who underwent breast cancer surgery between six and 48 months previously. Validated questionnaires were used to assess pain prevalence and impact, psychological distress, and upper limb function. Patients' clinical records were assessed for potential risk factors. RESULTS: Of the 375 patients who were sent questionnaires, 201 were included in the study. More than half of the patients (N = 111, 55%) reported breast surgery related-persistent pain, with 46 (23%) rating the pain as moderate to severe. Neuropathic pain was reported by 21 (46%) patients with moderate to severe pain. Pain interference, upper limb dysfunction, and psychological distress were significantly higher in patients with moderate to severe pain (P < 0.001). Non-European ethnicity (odds ratio [OR] = 5.02, 95% confidence interval [CI] = 2.05-12.25, P < 0.001), reconstruction surgery (OR = 4.10, 95% CI = 1.30-13.00, P = 0.02), and axillary node dissection (OR = 4.33, 95% CI = 1.19-15.73, P < 0.03) were identified as risk factors for moderate to severe pain by multivariate logistic regression analysis. CONCLUSIONS: Moderate to severe persistent pain after breast cancer surgery affects many New Zealand patients, and is associated with impaired daily life activities, physical disability, and psychological distress. Large numbers of patients undergo breast cancer surgery annually. This study emphasizes the importance of identification and management of these patients perioperatively.

Orthostatic intolerance following hip arthroplasty: incidence, risk factors and effect on length of stay: A prospective cohort study.

BACKGROUND: Early postoperative mobilisation is important for enhanced recovery, but can be hindered by orthostatic intolerance, characterised by dizziness, nausea, vomiting, feeling of heat, blurred vision and ultimately syncope. Although the incidence of orthostatic intolerance following total hip arthroplasty has been identified, few studies have yet investigated potential risk factors for developing orthostatic intolerance after hip arthroplasty. OBJECTIVES: The aim of this study was to assess the incidence of orthostatic intolerance on the first postoperative day after total hip arthroplasty, potential predisposing risk factors for developing orthostatic intolerance and its effect on length of stay. DESIGN: A prospective observational study. SETTING: Tertiary hospital, Auckland, New Zealand, May to September 2015. PATIENTS: One hundred and seventeen consecutive patients undergoing unilateral total hip arthroplasty. Patients were excluded if they had revision surgery. MAIN OUTCOME MEASURES: Incidence of orthostatic intolerance during mobilisation on the first postoperative day. Significant peri-operative risk factors for developing orthostatic intolerance were identified using logistic regression. Length of stay was compared between orthostatic intolerant and orthostatic tolerant patients using the Mann-Whitney U-test. RESULTS: On the first postoperative day, 22% of patients failed mobilisation due to orthostatic intolerance. Factors independently associated with orthostatic intolerance were female sex; OR (95% CI), 3.11 (1.01 to 9.57), postoperative use of gabapentin; OR 3.55 (1.24 to 10.15) and high peak pain levels (≥5/10) during mobilisation; OR 4.05 (1.30 to 12.61). Overall, 78% of patients were correctly identified. The model was more accurate at predicting those who would not get orthostatic intolerance (89% correct), compared with those who did have orthostatic intolerance (39% correct). Length of stay was longer in patients with orthostatic intolerance (P = 0.019). CONCLUSION: Orthostatic intolerance is common after total hip arthroplasty. Optimising pain control prior to mobilisation and limiting gabapentin use may modify the risk of developing postoperative orthostatic intolerance. Although personalised recovery pathways appear attractive, at present, the ability to predict at-risk individuals is still limited.

Structural Brain Alterations Before and After Total Knee Arthroplasty: A Longitudinal Assessment.

Objective: Many studies have provided evidence of altered brain structure in chronic pain conditions, as well as further adaptations following treatment that are coincident with changes in pain. Less is known regarding how these structural brain adaptations relate to assessments of nociceptive processing. The current study aimed to investigate brain structure in people with knee osteoarthritis (OA) before and after total knee arthroplasty (TKA) and to investigate the relationships between these findings and quantitative sensory testing (QST) of the nociceptive system. Methods: Twenty-nine people with knee OA underwent magnetic resonance imaging (MRI) scans and QST before and six months after TKA and were compared with a pain-free control group (N = 18). MRI analyses involved voxel-based morphometry and fractional anisotropy. Results: Before TKA, there was reduced gray matter volume and impaired fractional anisotropy in areas associated with nociceptive processing, with further gray matter adaptations and improvements in fractional anisotropy evident after TKA. QST revealed increased nociceptive facilitation and impaired inhibition in knee OA that was reversed after TKA. There were minimal relationships found between MRI data and QST assessments or pain report. Conclusions: In people with end-stage knee OA, region-specific gray matter atrophy was detected, with further changes in gray matter volume and improvements in white matter integrity observed after joint replacement. Despite coincident alterations in nociceptive inhibition and facilitation processes, there did not appear to be any association between these functional assessments of the nociceptive system and changes in brain structure.

Pain Catastrophizing is Not Associated With Spinal Nociceptive Processing in People With Chronic Widespread Pain.

OBJECTIVES: Pain catastrophizing has been associated with higher pain intensity, increased risk of developing chronic pain and poorer outcomes after treatment. Despite this, the mechanisms by which pain catastrophizing influences pain remain poorly understood. It has been hypothesized that pain catastrophizing may impair descending inhibition of spinal level nociception. The aims of this study were to compare spinal nociceptive processing in people with chronic widespread pain and pain-free controls and examine potential relationships between measures of pain catastrophizing and spinal nociception. MATERIALS AND METHODS: Twenty-six patients with chronic widespread pain and 22 pain-free individuals participated in this study. Spinal nociception was measured using the nociceptive flexion reflex (NFR) threshold and NFR inhibition, measured as the change in NFR area during exposure to a second, painful conditioning stimulus (cold water immersion). Pain catastrophizing was assessed using the Pain Catastrophizing Scale and a situational pain catastrophizing scale. RESULTS: Compared with pain-free controls, patients with chronic widespread pain had higher pain catastrophizing scores and lower NFR thresholds. Although NFR area was reduced by a painful conditioning stimulus in controls, this was not apparent in individuals with chronic widespread pain. No significant correlations were observed between measures of pain catastrophizing and spinal nociception. DISCUSSION: Despite increased excitability and decreased inhibition of spinal nociception in patients with chronic widespread pain, we could find no evidence of a significant relationship between pain catastrophizing and measures of spinal nociceptive processing.

The Association Between Corticomotor Excitability and Motor Skill Learning in People With Painful Hand Arthritis.

OBJECTIVES: Previous studies have shown a tendency for reduced motor cortex inhibition in chronic pain populations. People with chronic pain also routinely demonstrate motor deficiencies, including skill learning. The goals of the current study were to (1) provide a thorough analysis of corticomotor and intracortical excitability in people with chronic arthritic hand pain, and (2) examine the relationship between these measures and performance on a motor skill learning task. METHODS: Twenty-three people with arthritic hand pain and 20 pain-free controls participated in a cross-sectional study. Transcranial magnetic stimulation was used to assess corticomotor and intracortical excitability of the first dorsal interosseus muscle. Participants then completed a 30-minute motor skill training task involving the index finger of the same hand. RESULTS: Hand arthritis participants showed evidence of reduced intracortical inhibition and enhanced facilitation, which correlated with duration of hand pain. Arthritis participants were initially poorer at the motor skill task but over the total training time performance was equivalent between groups. There were no associations found between measures of intracortical excitability and motor skill learning. DISCUSSION: Our findings are the first to provide evidence of cortical disinhibition in people with painful arthritis, as previously demonstrated in other chronic pain populations. Cortical excitability changes may progress the longer pain persists, with increased pain duration being associated with greater cortical disinhibition. There was no evidence that these changes in cortical excitability are related to impaired motor function or skill learning.

Is Motor Cortical Excitability Altered in People with Chronic Pain? A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic pain is characterised by maladaptive neuroplasticity in many systems, including the motor system. There is evidence that patients with chronic pain demonstrate altered corticospinal and intracortical excitability; however, findings are inconsistent and existing literature in this area has not been systematically reviewed. OBJECTIVE: To systematically review studies examining corticospinal and intracortical excitability using transcranial magnetic stimulation in people with chronic pain compared to healthy controls and to provide a meta-analysis of study outcomes. METHODS: Databases were searched for controlled studies evaluating corticospinal and intracortical excitability in chronic pain conditions. Outcome measure data were entered into separate meta-analyses and effect sizes calculated. A subgroup analysis based on the type of chronic pain population was also performed. RESULTS: Forty-three studies were included, encompassing a pooled total of 1009 people with chronic pain and 658 control participants. Significant effect sizes (P < 0.05) indicated that in chronic pain populations the duration of the silent period and the extent of short-interval intracortical inhibition were both reduced and short-interval intracortical facilitation was enhanced. The subgroup analysis revealed that only the neuropathic pain group exhibited significant effect sizes for these outcome measures. Effect sizes for the remaining outcome measures were not significant CONCLUSIONS: There is evidence of motor cortex disinhibition in chronic pain populations, suggestive of a disruption in GABA-mediated intracortical inhibition. Disinhibition was more pronounced in populations with neuropathic pain. These findings provide new insights into the relationship between chronic pain and motor cortex excitability, which may have meaningful implications for the future treatment of chronic pain conditions.

Experimental knee pain impairs submaximal force steadiness in isometric, eccentric, and concentric muscle actions.

INTRODUCTION: Populations with knee joint damage, including arthritis, have noted impairments in the regulation of submaximal muscle force. It is difficult to determine the exact cause of such impairments given the joint pathology and associated neuromuscular adaptations. Experimental pain models that have been used to isolate the effects of pain on muscle force regulation have shown impaired force steadiness during acute pain. However, few studies have examined force regulation during dynamic contractions, and these findings have been inconsistent. The goal of the current study was to examine the effect of experimental knee joint pain on submaximal quadriceps force regulation during isometric and dynamic contractions. METHODS: The study involved fifteen healthy participants. Participants were seated in an isokinetic dynamometer. Knee extensor force matching tasks were completed in isometric, eccentric, and concentric muscle contraction conditions. The target force was set to 10 % of maximum for each contraction type. Hypertonic saline was then injected into the infrapatella fat pad to generate acute joint pain. The force matching tasks were repeated during pain and once more 5 min after pain had subsided. RESULTS: Hypertonic saline resulted in knee pain with an average peak pain rating of 5.5 ± 2.1 (0-10 scale) that lasted for 18 ± 4 mins. Force steadiness significantly reduced during pain across all three muscle contraction conditions. There was a trend to increased force matching error during pain but this was not significant. CONCLUSION: Experimental knee pain leads to impaired quadriceps force steadiness during isometric, eccentric, and concentric contractions, providing further evidence that joint pain directly affects motor performance. Given the established relationship between submaximal muscle force steadiness and function, such an effect may be detrimental to the performance of tasks in daily life. In order to restore motor performance in people with painful arthritic conditions of the knee, it may be important to first manage their pain more effectively.

Frequency, cost, and risk factors of readmissions among severe sepsis survivors.

OBJECTIVE: To determine the frequency, mortality, cost, and risk factors associated with readmission after index hospitalization with severe sepsis. DESIGN: Observational cohort study of Healthcare Cost and Utilization Project data. SETTING: All nonfederal hospitals in three U.S. states. PATIENTS: Severe sepsis survivors (n = 43,452) in the first two quarters of 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured readmission rates and the associated cost and mortality of readmissions in severe sepsis survivors. We used multivariable logistic regression to identify patient and hospitalization characteristics associated with readmission. Of 43,452 sepsis survivors, 26% required readmission within 30 days and 48% within 180 days. The cumulative mortality rate of sepsis survivors attributed to readmissions was 8%, and the estimated cost was over $1.1 billion. Among survivors, 25% required multiple readmissions within 180 days and accounted for 77% of all readmissions. Age younger than 80 years (odds ratio, 1.14; 95% CI, 1.08-1.21), black race (odds ratio, 1.18; 95% CI, 1.10-1.26), and Medicare or Medicaid payor status (odds ratio, 1.21; 95% CI, 1.13-1.30; odds ratio, 1.34; 95% CI, 1.23-1.46, respectively) were associated with greater odds of 30-day readmission while female gender was associated with reduced odds (odds ratio, 0.92; 95% CI, 0.87-0.96). Comorbidities including malignancy (odds ratio, 1.34; 95% CI, 1.24-1.45), collagen vascular disease (odds ratio, 1.30; 95% CI, 1.15-1.46), chronic kidney disease (odds ratio, 1.24; 95% CI, 1.18-1.31), liver disease (odds ratio, 1.22; 95% CI, 1.11-1.34), congestive heart failure (odds ratio, 1.14; 95% CI, 1.08-1.19), lung disease (odds ratio, 1.12; 95% CI, 1.06-1.18), and diabetes (odds ratio, 1.12; 95% CI, 1.07-1.17) were associated with greater odds of 30-day readmission. Index hospitalization characteristics including longer length of stay, discharge to a care facility, higher hospital annual severe sepsis case volume, and higher hospital sepsis mortality rate were also positively associated with readmission rates. CONCLUSION: The 30-day and 180-day readmissions are common in sepsis survivors with significant resultant cost and mortality. Patient sociodemographics and comorbidities as well as index hospitalization characteristics are associated with 30-day readmission rates.

Subconscious manipulation of pain expectation can modulate cortical nociceptive processing.

OBJECTIVE: To determine whether manipulation of the expectation of pain inhibition can enhance the efficacy of conditioned pain modulation in healthy participants METHODS: A conditioned pain modulation paradigm was used to investigate the effect of psychological manipulation of expectation on pain inhibition. In 19 healthy men, the lower limb nociceptive flexion reflex was elicited in isolation (test stimulus) and during application of 2 forms of conditioning stimuli. Following application of the first conditioning stimulus (CS1), the participants were informed that the subsequent conditioning stimulus (CS2) would elicit a greater amount of inhibition of test pain compared with the first. Lower limb flexion reflex size, perceived pain ratings of the test stimulus, and ratings of expected pain modulation were obtained for both test and conditioning protocols. RESULTS: The inhibition of perceived pain was significantly greater with CS2 compared with CS1; however, there was no significant difference in inhibition of nociceptive flexion reflex size or the participant's reported expectation of pain modulation between the 2 conditioning stimuli. DISCUSSION: As perceived pain inhibition was enhanced but flexion reflex size unchanged following the intervention, we suggest that the intervention gave rise to an inhibition of ascending nociceptive information at a supraspinal level resulting in reduced pain perception without influencing spinal level processing of nociceptive input. The finding that conditioned pain modulation can be enhanced is of relevance to clinical pain populations who commonly show impaired inhibition.