Alpha -receptor agonists as adjuvants for brachial plexus nerve blocks-A systematic review with meta-analyses.

Background: We review the efficacy and safety of dexmedetomidine and clonidine as perineural or systemic adjuvants for brachial plexus blocks (BPB).

Methods: We included randomised controlled trials on upper limb surgery with BPBs in adults, comparing dexmedetomidine with clonidine or either drug with placebo. The primary outcome was duration of analgesia.

Benefits and harm of paracetamol and ibuprofen in combination for post-operative pain: Pre-planned subgroup analyses of the multicenter, randomized PANSAID trial.

Background: The "Paracetamol and Ibuprofen in Combination" (PANSAID) trial showed that combining paracetamol and ibuprofen resulted in lower opioid consumption than each drug alone and we did not find an increase in risk of harm when using ibuprofen vs paracetamol. The aim of this subgroup analysis was to investigate the differences in benefits and harms of the interventions in different subgroups. We hypothesized that the intervention effects would differ in subgroups with different risk of pain or adverse events.

Pain management after total hip arthroplasty at five different Danish hospitals: A prospective, observational cohort study of 501 patients.

Background: The available literature does not present a "gold standard" for post-operative pain treatment after total hip arthroplasty (THA). The aim of this prospective observational study was to explore and document post-operative pain treatment, including outcomes, in a large cohort of patients undergoing THA at five different Danish hospitals.

Methods: This prospective, multicentre, observational cohort study of 501 THA patients was performed at five different hospitals in the Capital Region and at the Region Zealand in Denmark, from April 2014 to April 2016.

Effect of Combination of Paracetamol (Acetaminophen) and Ibuprofen vs Either Alone on Patient-Controlled Morphine Consumption in the First 24 Hours After Total Hip Arthroplasty: The PANSAID Randomized Clinical Trial.

Importance: Multimodal postoperative analgesia is widely used but lacks evidence of benefit.

Objective: Investigate beneficial and harmful effects of 4 nonopioid analgesics regimens.

Design, Setting, And Participants: Randomized, blinded, placebo-controlled, 4-group trial in 6 Danish hospitals with 90-day follow-up that included 556 patients undergoing total hip arthroplasty (THA) from December 2015 to October 2017.

Systemic dexmedetomidine is not as efficient as perineural dexmedetomidine in prolonging an ulnar nerve block.

Background: We tested the joint hypotheses that both perineural and systemic dexmedetomidine prolong the duration of an ulnar nerve block (UNB) compared with ropivacaine alone and that systemic dexmedetomidine is noninferior compared with perineural dexmedetomidine in block prolongation.

Methods: We performed bilateral UNBs in 22 healthy volunteers on two separate days. On the first day, each arm was randomized to either 4 mL ropivacaine 5 mg/mL+1 mL dexmedetomidine 100 µg/mL (Perineural) or 4 mL ropivacaine 5 mg/mL+1 mL saline (Systemic).

Brain resting-state connectivity in the development of secondary hyperalgesia in healthy men.

Central sensitization is a condition in which there is an abnormal responsiveness to nociceptive stimuli. As such, the process may contribute to the development and maintenance of pain. Factors influencing the propensity for development of central sensitization have been a subject of intense debate and remain elusive.

Intraoperative S-ketamine for the reduction of opioid consumption and pain one year after spine surgery: A randomized clinical trial of opioid-dependent patients.

Background: We aimed to explore the effect of intraoperative S-ketamine on analgesic consumption and pain one year after spine surgery in chronic opioid-dependent patients undergoing spinal fusion surgery.

Methods: Single-centre, randomized, blinded trial of 147 patients.

Intervention: Perioperative S-ketamine bolus 0.

The association between areas of secondary hyperalgesia and volumes of the caudate nuclei and other pain relevant brain structures-A 3-tesla MRI study of healthy men.

Introduction: Central sensitization plays a pivotal role in maintenance of pain and is believed to be intricately involved in several chronic pain conditions. One clinical manifestation of central sensitization is secondary hyperalgesia. The degree of secondary hyperalgesia presumably reflects individual levels of central sensitization.

Adductor Canal Block With Continuous Infusion Versus Intermittent Boluses and Morphine Consumption: A Randomized, Blinded, Controlled Clinical Trial.

Background: Based on the assumption that relatively large volumes of local anesthetic optimize an adductor canal block (ACB), we theorized that an ACB administered as repeated boluses would improve analgesia without compromising mobility, compared with a continuous infusion.

Methods: We performed a randomized, blinded, controlled study, including patients scheduled for total knee arthroplasty with spinal anesthesia. Patients received 0.

Heterogenic control groups in randomized, controlled, analgesic trials of total hip and knee arthroplasty.

Introduction: Postoperative analgesic interventions are often tested adjunct to basic non-opioid analgesics in randomized controlled trials (RCTs). Consequently, treatment in control groups, and possible assay sensitivity, differs between trials. We hypothesized that postoperative opioid requirements and pain intensities vary between different control groups in analgesic trials.

Dose-related beneficial and harmful effects of gabapentin in postoperative pain management - post hoc analyses from a systematic review with meta-analyses and trial sequential analyses.

Background: During the last 15 years, gabapentin has become an established component of postoperative pain treatment. Gabapentin has been employed in a wide range of doses, but little is known about the optimal dose, providing the best balance between benefit and harm. This systematic review with meta-analyses aimed to explore the beneficial and harmful effects of various doses of gabapentin administered to surgical patients.

PANSAID-PAracetamol and NSAID in combination: detailed statistical analysis plan for a randomised, blinded, parallel, four-group multicentre clinical trial.

Background: Effective postoperative pain management is essential for the rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic effects and safety of the combination of paracetamol and ibuprofen. This paper describes in detail the statistical analysis plan for the primary publication to prevent outcome reporting bias and data-driven analysis results.

Clonidine used as a perineural adjuvant to ropivacaine, does not prolong the duration of sensory block when controlling for systemic effects: A paired, blinded, randomized trial in healthy volunteers.

Background: Clonidine used as an adjuvant to ropivacaine have been shown to prolong the duration of peripheral nerve blocks. The mechanism of action remains unclear. We hypothesized, that clonidine used as an adjuvant to ropivacaine extends the duration of an adductor canal block (ACB) by a peripheral mechanism, compared to ropivacaine alone when controlling for systemic effects.

Gabapentin in procedure-specific postoperative pain management - preplanned subgroup analyses from a systematic review with meta-analyses and trial sequential analyses.

Background: It has been argued that postoperative pain treatment should be "procedure-specific", since different analgesics may have specific effects dependent on the surgical procedure. The aim of the present subgroup analysis was to compare the beneficial and harmful effects of perioperative gabapentin treatment in different surgical procedures.

Methods: Relevant databases were searched for randomized clinical trials (RCTs) comparing gabapentin versus placebo.

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.

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.

PANSAID - PAracetamol and NSAID in combination: study protocol for a randomised trial.

Background: Effective postoperative pain management is essential for the rehabilitation of the surgical patient. No 'gold standard' exists after total hip arthroplasty (THA) and combinations of different nonopioid medications are used with virtually no evidence for additional analgesic efficacy compared to monotherapy. The objective of this trial is to investigate the analgesic effects and safety of paracetamol and ibuprofen alone and in combination in different dosages after THA.

Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: a randomized, blinded trial.

Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would reduce immediate postoperative opioid consumption compared with placebo in chronic pain patients with opioid dependency undergoing lumbar spinal fusion surgery.

The effect of preoperative dexamethasone on pain 1 year after lumbar disc surgery: a follow-up study.

Background: It has been hypothesized that dexamethasone can inhibit persistent postoperative pain, but data on humans is lacking and results from animal studies are conflicting. We explored the effect of 16 mg dexamethasone IV administered preoperatively on persistent pain 1 year after lumbar discectomy.

Methods: This is a prospective 1-year follow-up on a single-centre, randomized, and blinded trial exploring the analgesic effect of 16 mg IV dexamethasone or placebo after lumbar discectomy.

Does Dexmedetomidine Have a Perineural Mechanism of Action When Used as an Adjuvant to Ropivacaine?: A Paired, Blinded, Randomized Trial in Healthy Volunteers.

Background: Dexmedetomidine used as an adjuvant to local anesthetics may prolong the duration of peripheral nerve blocks. Whether this is mediated by a perineural or systemic mechanism remains unknown. The authors hypothesized that dexmedetomidine has a peripheral mechanism of action.

Effect of Total Dose of Lidocaine on Duration of Adductor Canal Block, Assessed by Different Test Methods: A Report of Two Blinded, Randomized, Crossover Studies in Healthy Volunteers.

Background: The binary aims of this study were to investigate the effect of total dose of lidocaine on duration of an adductor canal block (ACB) and to validate different methods used to assess nerve blocks.

Methods: We performed 2 blinded, randomized, controlled crossover trials, including healthy, young men. In study 1, 14 subjects received 4 ACBs with saline and 40, 80, and 160 mg lidocaine.

Transversus abdominis plane block after laparoscopic colonic resection in cancer patients: A randomised clinical trial.

Background: A key point in pathways for optimal rehabilitation and enhanced recovery is an effective postoperative multimodal pain treatment regimen.

Objective: To investigate the analgesic effects of transversus abdominis plane (TAP) block in conjunction with paracetamol and ibuprofen in patients undergoing laparoscopic colonic resection.

Design: Randomised placebo-controlled double-blind study.

Is the Volume of the Caudate Nuclei Associated With Area of Secondary Hyperalgesia? - Protocol for a 3-Tesla MRI Study of Healthy Volunteers.

Background: Experience and development of pain may be influenced by a number of physiological, psychological, and psychosocial factors. In a previous study we found differences in neuronal activation to noxious stimulation, and microstructural neuroanatomical differences, when comparing healthy volunteers with differences in size of the area of secondary hyperalgesia following a standardized burn injury.

Objective: We aim to investigate the degree of association between the volume of pain-relevant structures in the brain and the size of the area of secondary hyperalgesia following brief thermal sensitization.

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.