Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Persistent postsurgical pain is common and affects quality of life. The hypothesis was that use of pregabalin and ketamine would prevent persistent pain after cardiac surgery. Methods This randomized, double-blind, placebo-controlled trial was undertaken at two cardiac surgery centers in the United Kingdom. Adults without chronic pain and undergoing any elective cardiac surgery patients via sternotomy were randomly assigned to receive either usual care, pregabalin (150 mg preoperatively and twice daily for 14 postoperative days) alone, or pregabalin in combination with a 48-h postoperative infusion of intravenous ketamine at 0.1 mg · kg−1 · h−1. The primary endpoints were prevalence of clinically significant pain at 3 and 6 months after surgery, defined as a pain score on the numeric rating scale of 4 or higher (out of 10) after a functional assessment of three maximal coughs. The secondary outcomes included acute pain, opioid use, and safety measures, as well as long-term neuropathic pain, analgesic requirement, and quality of life. Results In total, 150 patients were randomized, with 17 withdrawals from treatment and 2 losses to follow-up but with data analyzed for all participants on an intention-to-treat basis. The prevalence of pain was lower at 3 postoperative months for pregabalin alone (6% [3 of 50]) and in combination with ketamine (2% [1 of 50]) compared to the control group (34% [17 of 50]; odds ratio = 0.126 [0.022 to 0.5], P = 0.0008; and 0.041 [0.0009 to 0.28], P < 0.0001, respectively) and at 6 months for pregabalin alone (6% [3 of 50]) and in combination with ketamine 0% (0 of 5) compared to the control group (28% [14 of 50]; odds ratio = 0.167 [0.029 to 0.7], P = 0.006; and 0.000 [0 to 0.24], P < 0.0001). Diplopia was more common in both active arms. Conclusions Preoperative administration of 150 mg of pregabalin and postoperative continuation twice daily for 14 days significantly lowered the prevalence of persistent pain after cardiac surgery.

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Paracetamol is arguably the most commonly used analgesic and antipyretic drug worldwide, however its mechanism of action is still not fully established. It has been shown to exert effects through multiple pathways, some actions suggested to be mediated via N-arachidonoylphenolamine (AM404). AM404, formed through conjugation of paracetamol-derived p-aminophenol with arachidonic acid in the brain, is an activator of the capsaicin receptor, TRPV1, and inhibits the reuptake of the endocannabinoid, anandamide, into postsynaptic neurons, as well as inhibiting synthesis of PGE2 by COX-2. However, the presence of AM404 in the central nervous system following administration of paracetamol has not yet been demonstrated in humans. Cerebrospinal fluid (CSF) and blood were collected from 26 adult male patients between 10 and 211 minutes following intravenous administration of 1 g of paracetamol. Paracetamol was measured by high-performance liquid chromatography with UV detection. AM404 was measured by liquid chromatography-tandem mass spectrometry. AM404 was detected in 17 of the 26 evaluable CSF samples at 5–40 nmol⋅L−1. Paracetamol was measurable in CSF within 10 minutes, with a maximum measured concentration of 60 μmol⋅L−1 at 206 minutes. This study is the first to report on the presence of AM404 in human CSF following paracetamol administration. This may represent an important finding in our understanding of paracetamol’s mechanism of action, although measured concentrations were far below the previously documented IC50 for this metabolite.

Background: Sacroiliac joint (SIJ) pain is considered to be the third most common cause of low back pain with the prevalence of 13-25% in all low back pain patients. Its diagnosis and treatment remain a challenge with the poor evidence base for interventional procedures. Patients with SIJ pain experience a low quality of life, worse than some of the chronic health conditions. Simplicity radiofrequency (RF) neurotomy is a novel technique which tackles some of the problems faced by conventional RF neurotomy and may offer better results in managing pain arising from SIJ. Aim: The purpose of this retrospective review of practice was to look into the effectiveness of Simplicity RF neurotomy in terms of pain relief, quality of health improvement in patients suffering from SIJ pain and complications associated with the procedure. Methodology: Retrospective review of the patients undergoing Simplicity RF neurotomy at a tertiary hospital (April 2012 to June 2013). Pain scores and responses to SF (Short Form) 12 questionnaire before and at 12 months after treatment were compared using the Wilcoxon signed-rank test. Results: Out of 26 patients, 16 were considered for analysis. There was statistically significant reduction in both mean pain score (Numerical Rating Scale, NRS from 8.8 pre-intervention to 4.3 post-intervention) and median pain score (NRS from 9 pre-intervention to 5 post-intervention) with a p-value of <0.001 at 12 months. Reduction in the inter-quartile range of pain score was observed from 8-10 to 2.25-6 (p-value of <0.001). Global health as per SF12 scores showed statistically significant improvement, except in some of the psychological subcategories. The procedure-related pain was the only complication noted. Conclusion: From our data, we can conclude that Simplicity RF neurotomy of lateral branches of S1-S3 along with conventional RF denervation of L5 dorsal ramus may improve pain scores and many components of global health in carefully selected patients.