Systematic reviews and quality assessment of patient-reported outcome measures for physical function in comparative effectiveness studies regarding acute postoperative pain after total knee arthroplasty-Do we need to start all over again?

BACKGROUND AND OBJECTIVE: Recently, a consensus process specified a core outcome set (COS) of domains to be assessed in each comparative effectiveness research and clinical practice related to acute postoperative pain. Physical function (PF) was one of these domains. The aim of this review was to investigate which patient-reported outcome measures (PROMs) are used to assess PF after total knee arthroplasty (TKA) in clinical trials and if they fulfil basic requirements for a COS of PROMs based on their psychometric properties. METHODS: A systematic review of randomized controlled trials and observational studies based on a search in MEDLINE, EMBASE and CENTRAL was undertaken. PROMs and performance measures were extracted and investigated, including evaluation of psychometric properties of PROMs based on COSMIN recommendations. RESULTS: From initially 2896 identified records, 479 studies were included in the qualitative synthesis. Only 87 of these trials (18%) assessed PF using PROMs, whereas especially performance outcome measures were used in 470 studies (98%). Application of the 'COSMIN Risk-of-Bias-Box 1' to 13 of the 14 identified PROMs resulted in insufficient content validity of the included PROMs regarding the target population based on the inauguration or development articles. CONCLUSION: Our data indicate that a patient-centred postoperative assessment of PF in pain-related clinical trials early after TKA is not common, even though patient-reported assessment is widely recommended. In addition, none of the applied PROMs shows content validity based on their inauguration or development articles for the assessment of postoperative pain-related PF after TKA. SIGNIFICANCE: A systematic search for patient-reported outcome measures assessing postoperative, pain-related physical function after total knee arthroplasty in clinical trials and assessment of their content validity revealed none that fulfilled requirements based on COSMIN recommendations.

Spinal GABA transporter 1 contributes to evoked-pain related behavior but not resting pain after incision injury.

The inhibitory function of GABA at the spinal level and its central modulation in the brain are essential for pain perception. However, in post-surgical pain, the exact mechanism and modes of action of GABAergic transmission have been poorly studied. This work aimed to investigate GABA synthesis and uptake in the incisional pain model in a time-dependent manner. Here, we combined assays for mechanical and heat stimuli-induced withdrawal reflexes with video-based assessments and assays for non-evoked (NEP, guarding of affected hind paw) and movement-evoked (MEP, gait pattern) pain-related behaviors in a plantar incision model in male rats to phenotype the effects of the inhibition of the GABA transporter (GAT-1), using a specific antagonist (NO711). Further, we determined the expression profile of spinal dorsal horn GAT-1 and glutamate decarboxylase 65/67 (GAD65/67) by protein expression analyses at four time points post-incision. Four hours after incision, we detected an evoked pain phenotype (mechanical, heat and movement), which transiently ameliorated dose-dependently following spinal inhibition of GAT-1. However, the NEP-phenotype was not affected. Four hours after incision, GAT-1 expression was significantly increased, whereas GAD67 expression was significantly reduced. Our data suggest that GAT-1 plays a role in balancing spinal GABAergic signaling in the spinal dorsal horn shortly after incision, resulting in the evoked pain phenotype. Increased GAT-1 expression leads to increased GABA uptake from the synaptic cleft and reduces tonic GABAergic inhibition at the post-synapse. Inhibition of GAT-1 transiently reversed this imbalance and ameliorated the evoked pain phenotype.

Systematic Review on Pain-Related Outcome Domains After Sternotomy: A First Step Toward the Development of a Core Outcome Set.

OBJECTIVES: Pain after surgery has a major impact on acute and long-term recovery and quality of life, but its management is often insufficient. To enhance the quality of research and to allow for better comparability between studies, it is important to harmonize outcomes for assessing the efficacy and effectiveness of pain management interventions after surgery. As a first step in developing a core outcome set, this study aimed to systematically search for outcome domains assessed in research regarding acute pain management after sternotomy as an example of a typically painful surgical procedure. METHODS: A systematic literature review was performed using MEDLINE, Embase, and CENTRAL. Eligibility criteria consisted of randomized controlled trials and observational trials targeting pain management after sternotomy in adults in the acute postoperative setting (≤2 weeks). After duplicate removal and title and abstract screening by 2 independent reviewers, study characteristics and outcome domains were identified, which were extracted from full texts and summarized qualitatively. RESULTS: Of 1350 studies retrieved by database searching, 156 studies were included for full-text extraction. A total of 80 different outcome domains were identified: pain intensity, analgesic consumption, physiological function, and adverse events were the most frequent ones. Outcome domains were often not explicitly reported, and the combination of domains and assessment tools was heterogeneous. The choice of outcomes is commonly made within clinicians; patients' perspectives are not considered. CONCLUSIONS: The wide variety of commonly applied outcome domains, the nonexplicit wording, and the heterogeneous combination of the domains indicating treatment benefit demonstrate the need for harmonization of outcomes assessing perioperative pain management after surgery.

Influence of transcutaneous spinal stimulation on human LTP-like pain amplification. A randomized, double-blind study in volunteers.

OBJECTIVE: Transcutaneous spinal direct current stimulation (tsDCS) has been proven to affect nociceptive signal processing. We designed a randomized, double-blind, cross-over study to investigate whether tsDCS applied before or after inducing long-term potentiation-(LTP)-like hyperalgesia may decrease nociceptive sensitivity. METHODS: In healthy volunteers, tsDCS (2.5mA, 15min) was applied to the thoracic spine prior (n=14) or immediately following (n=12) electrical high-frequency stimulation (HFS) to the thigh, inducing hyperalgesia. Mechanical and electrical perception were assessed before HFS stimulation and at three time points following HFS stimulation (all within 90min of HFS). Subjects took part in three separate sessions to test effects of anodal, cathodal, or sham tsDCS. RESULTS: Within 60minHFS led to unilateral changes on the conditioned side: mechanical pain thresholds tended to decrease and electrical detection thresholds significantly decreased (p<0.001); pain ratings measured using the numerical rating scale (NRS) increased for electrical stimuli (p<0.01) and two categories of mechanical stimuli ("Light(8-64mN)": p=ns; "Heavy(128-512mN)": p<0.01). Irrespective of stimulation order or polarity, tsDCS could not influence nociceptive sensitivity. CONCLUSION: Hyperalgesia was adequately induced, but tsDCS had no effect on HFS-induced sensitization. SIGNIFICANCE: While tsDCS has been shown to affect pain measures, our results suggest irrespective of time of stimulation or polarity that tsDCS may be less effective in modulating pain in a sensitized state in healthy subjects.

[Survey of pain after ambulatory surgery: An internet-based instrument]. / Erhebung von Schmerzen nach ambulanten Operationen : Ein internetbasiertes Instrument.

BACKGROUND AND AIM: Pain after surgery continues to be undermanaged. Studies and initiatives aiming to improve the management of postoperative pain are growing; however, most studies focus on inpatients and pain on the first day after surgery. The management of postoperative pain after ambulatory surgery and for several days thereafter is not yet a major focus. One reason is the low return rate of the questionnaires in the ambulatory sector. This article reports the development and feasibility of a web-based electronic data collection system to examine pain and pain-related outcome on predefined postoperative days after ambulatory surgery. MATERIAL AND METHODS: In this prospective pilot study 127 patients scheduled for ambulatory surgery were asked to participate in a survey to evaluate aspects related to pain after ambulatory surgery. The data survey was divided in (1) a preoperative, intraoperative and postoperative part and (2) a postoperative internet-based electronic questionnaire which was sent via e-mail link to the patient on days 1, 3 and 7 after surgery. A software was developed using a PHP-based platform to send e-mails and retrieve the data after web-based entries via a local browser. Feasibility, internet-based hitches and compliance were assessed by an additional telephone call after day 7. RESULTS: A total of 100 patients (50 female) between 18 and 71 years (mean 39.1 ± 12.7 years) were included in the pilot study. Return rates of the electronic questionnaires were 86% (days 3 and 7) and 91% (day 1 after surgery). All 3 electronic questionnaires were answered by 82% of patients. Aspects influencing the return rate of questionnaires were work status but not age, gender, education level and preoperative pain. Telephone interviews were performed with 81 patients and revealed high operability of the internet-based survey without any major problems. CONCLUSION: The user-friendly feasibility and operability of this internet-based electronic data survey system explain the high compliance and return rate of electronic questionnaires by patients at home after ambulatory surgery. This survey tool therefore provides unique opportunities to evaluate and improve postoperative pain management after ambulatory surgery.

[Postoperative pain therapy in Germany. Status quo]. / Therapie postoperativer Schmerzen in Deutschland. Aktueller Stand.

A great deal of progress has been made in the field of postoperative pain therapy in the last 20 years. Beginning from clinical trials on the effectiveness of individual procedures, such as epidural anesthesia and patient-controlled analgesia, a wide range of healthcare services research as well as basic research with human and animal experiments has been established. Whereas health services research in the 1980s and 1990s focused more on the implementation of acute pain services, outcome-oriented research approaches are nowadays the center of attention. Acute pain registries and pain certification projects initiated in Germany have to be mentioned particularly in this respect. Basic research papers from recent years increasingly address specific aspects of acute postoperative pain and have provided translational approaches that are applied around the world for studying neurobiological mechanisms of postoperative pain. At the same time, interdisciplinary cooperation in research projects has led to a better understanding of complex correlations regarding predictors and mechanisms (including psychosocial aspects) of acute and in recent times also chronic pain after surgery. In parallel, evidence-based medicine has found its way into acute pain medicine in Germany. In 2007, clinical acute pain therapy in Germany was enhanced by S3 level guidelines for the first time; however, the implementation is still incomplete. In future, questions concerning mechanism-based therapy of acute pain need to be equally in the center of attention of research, such as prevention of persisting pain after surgery and acute pain of different origins.

[Pain medicine from intercultural and gender-related perspectives]. / Schmerzmedizin aus einer interkulturellen und geschlechterspezifischen Perspektive.

Cultural setting and sex and gender of the patient are important factors affecting the occurrence, severity, clinical course and prognosis of pain and pain-related diseases. Intercultural differences in the perception and verbal expression of symptoms and emotional function are fundamental and it is important to realize these differences in order to understand patients with a migration background. A trusting doctor-patient relationship is generally very sensitive and it is even more difficult to establish when differences in the cultural background impair mutual understanding. Regarding sex and gender there is evidence that females are more susceptible to developing chronic pain conditions, experience more severe pain and respond differently to pain therapy; however, results of recent studies indicate that females are not that different to males when comparing several modalities of experimental pain (although some differences exist). Similarly, sex and gender differences in postoperative pain seem to exist but the differences are relatively small when pain scores are compared. Other aspects, such as the response to analgesics and role of psychosocial factors should be addressed when sex and gender aspects are studied. Similarly, sex and gender differences in the prevalence of chronic pain exist but the results of some studies, e.g. those controlling for confounders, are not very clear. Research is needed to delineate the role of specific aspects affecting sex and gender differences and the underlying mechanisms (e.g. reduced inhibitory control, hormones, psychological aspects and social factors). Altogether, we need to open our minds to some intercultural and sex and gender aspects in the clinical setting. For sex and gender differences we may need a more biopsychosocial approach to understand the underlying differences and differentiate between sex and gender and sex and gender-associated aspects for acute and chronic pain.