Heat pain detection threshold is associated with the area of secondary hyperalgesia following brief thermal sensitization:a study of healthy male volunteers

INTRODUCTION: The area of secondary hyperalgesia following brief thermal sensitization (BTS) of the skin and heat pain detection thresholds (HPDT) may both have predictive abilities in regards to pain sensitivity and clinical pain states. The association between HPDT and secondary hyperalgesia, however, remains unsettled, and the dissimilarities in physiologic properties suggest that they may represent 2 distinctively different pain entities. The aim of this study was to investigate the association between HPDT and BTS-induced secondary hyperalgesia. METHODS: A sample of 121 healthy male participants was included and tested on 2 separate study days with BTS (45°C, 3 minutes), HPDT, and pain during thermal stimulation (45°C, 1 minute). Areas of secondary hyperalgesia were quantified after monofilament pinprick stimulation. The pain catastrophizing scale (PCS) and hospital anxiety and depression scale (HADS) were also applied. RESULTS: A significant association between HPDT and the size of the area of secondary hyperalgesia (p<0.0001) was found. The expected change in area of secondary hyperalgesia due to a 1-degree increase in HPDT was estimated to be −27.38 cm(2), 95% confidence interval (CI) of −37.77 to −16.98 cm(2), with an R(2) of 0.19. Likewise, a significant association between HADS-depression subscore and area of secondary hyperalgesia (p=0.046) was found, with an estimated expected change in secondary hyperalgesia to a 1-point increase in HADS-depression subscore of 11 cm(2), 95% CI (0.19–21.82), and with R(2) of 0.03. We found no significant associations between secondary hyperalgesia area and PCS score or pain during thermal stimulation. CONCLUSION: HPDT and the area of secondary hyperalgesia after BTS are significantly associated; however, with an R(2) of only 19%, HPDT only offers a modest explanation of the inter-participant variation in the size of the secondary hyperalgesia area elicited by BTS

Is heat pain detection threshold associated with the area of secondary hyperalgesia following brief thermal sensitization?:A study of healthy volunteers - design and detailed plan of analysis

BACKGROUND: Several factors are believed to influence the development and experience of pain. Human clinical pain models are central tools, in the investigation of basic physiologic pain responses, and can be applied in patients as well as in healthy volunteers. Each clinical pain model investigates different aspects of the human pain response. Brief thermal sensitization induces a mild burn injury, resulting in development of primary hyperalgesia at the site of stimulation, and secondary hyperalgesia surrounding the site of stimulation. Central sensitization is believed to play an important role in the development of secondary hyperalgesia; however, a possible association of secondary hyperalgesia following brief thermal sensitization and other heat pain models remains unknown. Our aim with this study is to investigate how close the heat pain detection threshold is associated with the size of the area of secondary hyperalgesia induced by the clinical heat pain model: Brief thermal sensitization. METHODS AND DESIGN: We aim to include 120 healthy participants. The participants will be tested on two separate study days with the following procedures: i) Brief thermal sensitization, ii) heat pain detection threshold and iii) pain during thermal stimulation. Additionally, the participants will be tested with the Pain Catastrophizing Scale and Hospital Anxiety and Depression Scale questionnaires. We conducted statistical simulations based on data from our previous study, to estimate an empirical power of 99.9 % with α of 0.05. We define that an R(2) < 0.25 and predictive intervals larger than +/−150 cm(2) are indications of a weak association. DISCUSSION: The area of secondary hyperalgesia may serve as a quantitative measure of the central sensitization induced by cutaneous heat stimulation, and thus may be a biomarker of an individual’s pain sensitivity. The number of studies investigating secondary hyperalgesia is growing; however basic knowledge of the physiologic aspects of secondary hyperalgesia in humans is still incomplete. We therefore find it interesting to investigate if HPDT, a known quantitative sensory test, is associated with areas of secondary hyperalgesia following brief thermal sensitization TRIAL REGISTRATION: Clinicaltrials.gov (Identifier: NCT02527395). Danish Research Ethics Committee (Identifier: H-8-2014-012). Danish Data Protection Agency (Identifier: 30-1436). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12871-016-0193-2) contains supplementary material, which is available to authorized users

Correction: The Area of Secondary Hyperalgesia following Heat Stimulation in Healthy Male Volunteers: Inter- and Intra-Individual Variance and Reproducibility.

[This corrects the article DOI: 10.1371/journal.pone.0155284.]

Postoperative pain treatment after total knee arthroplasty: A systematic review

<div><p>Introduction</p><p>The aim of this systematic review was to document efficacy, safety and quality of evidence of analgesic interventions after total knee arthroplasty (TKA).</p><p>Methods</p><p>This PRISMA-compliant and PROSPERO-registered review includes all-language randomized controlled trials of medication-based analgesic interventions after TKA. Bias was evaluated according to Cochrane methodology. Outcomes were opioid consumption (primary), pain scores at rest and during mobilization, adverse events, and length of stay. Interventions investigated in three or more trials were meta-analysed. Outcomes were evaluated using forest plots, Grading of Recommendations Assessment, Development and Evaluation (GRADE), L’Abbe Plots and trial sequential analysis.</p><p>Results</p><p>The included 113 trials, investigating 37 different analgesic interventions, were characterized by unclear/high risk of bias, low assay sensitivity and considerable differences in pain assessment tools, basic analgesic regimens, and reporting of adverse events. In meta-analyses single and continuous femoral nerve block (FNB), intrathecal morphine, local infiltration analgesia, intraarticular injection of local anaesthetics, non-steroidal anti-inflammatory drugs, and gabapentinoids demonstrated significant analgesic effects. The 24-hour morphine-sparing effects ranged from 4.2 mg (CI: 1.3, 7.2; intraarticular local anaesthetics), to 16.6 mg (CI: 11.2, 22; single FNB). Pain relieving effects at rest at 6 hours ranged from 4 mm (CI: -10, 2; gabapentinoids), to 19 mm (CI: 8, 31; single FNB), and at 24 hours from 3 mm (CI: -2, 8; gabapentinoids), to 16 mm (CI: 8, 23; continuous FNB). GRADE-rated quality of evidence was generally low.</p><p>Conclusion</p><p>A low quality of evidence, small sample sizes and heterogeneity of trial designs prohibit designation of an optimal procedure-specific analgesic regimen after TKA.</p></div