The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial
The Effect of Preoperative Intra-Articular Methylprednisolone on Pain after TKA: a Randomized Double-Blinded Placebo Controlled Trial in Patients with High-Pain Knee Osteoarthritis and Sensitization.
In a randomized, double-blind, placebo controlled trial, we investigated the postoperative analgesic effect of a single intra-articular injection of 40 mg methylprednisolone acetate (MP) administered 1 week before total knee arthroplasty (TKA). Forty-eight patients with high pain osteoarthritis (≥5 on a numeric rating scale during walk) and sensitization (pressure pain threshold <250 kPa), aged 50 to 80 years and scheduled for primary unilateral TKA under spinal anaesthesia were included. ⋯ No difference in the proportion of patients with moderate/severe pain was found between MP/placebo groups at 24 hours (67% and 74%, χ2 = .2, P = .63, odds ratio = .7, 95% confidence interval = .2-2.8) or at 48 hours (57% and 68%, χ2 = .5, P = .46, odds ratio = .6, 95% confidence interval = .2-2.3), and no difference between groups in postoperative sensitization was found (P > .4) despite reduced preoperative intra-articular inflammation (IL-6) in the MP group versus placebo (median change in IL-6 = -70 pg/mL, interquartile range = -466 to 0 vs. 32 pg/mL, interquartile range = -26 to 75, P = .029). Alternative central or peripheral analgesic interventions in this high-risk group are required.
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Comparative Study
Novel Endomorphin Analogs are More Potent and Longer Lasting Analgesics in Neuropathic, Postoperative, Inflammatory, and Visceral Pain Relative to Morphine.
Activation of the mu-opioid receptor provides the gold standard for pain relief, but most opioids used clinically have adverse effects that have contributed to an epidemic of overdose deaths. We recently characterized mu-opioid receptor selective endomorphin (EM) analogs that provide potent antinociception with reduction or absence of a number of side effects of traditionally prescribed opioids including abuse liability, respiratory depression, motor impairment, tolerance, and inflammation. The current study explores the effectiveness of these EM analogs relative to morphine in four major pain models by intrathecal as well as intravenous administration in male Sprague Dawley rats and subcutaneous administration in male CD-1 mice. In the spared nerve injury model of neuropathic pain, mechanical allodynia and mechanical hyperalgesia were assessed with von Frey and Randall-Selitto tests, respectively. In the paw incision model of postoperative pain, von Frey testing was used to assess mechanical allodynia and thermal hyperalgesia was evaluated with Hargreaves testing. In the Complete Freund's Adjuvant model of inflammatory pain, thermal hyperalgesia was assessed using Hargreaves testing. In CD-1 mice, visceral pain was assessed with the acetic acid writhing test. In all cases, EM analogs had equal or greater potency and longer duration of action relative to morphine. The data suggest that EM analogs, particularly analog 4 (ZH853), could provide effective therapy for a diverse spectrum of pain conditions with low risk of adverse side effects compared with currently used opioids such as morphine. ⋯ Novel EM analogs show equal or greater potency and effectiveness relative to morphine in multiple pain models. Together with substantially reduced side effects, including abuse liability, the compounds show promise for addressing the critical need for effective pain relief as well as reducing the opioid overdose epidemic.
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Randomized Controlled Trial
Chronic opioid therapy modifies QST changes following ketamine infusion in chronic pain patients.
The long-term effects of opioids on sensitization processes are believed to be mediated through the N-methyl-D-aspartate receptor. Quantitative sensory testing (QST) changes observed after a ketamine infusion have been previously described but the effect that chronic opioids will have is not known. The results of this prospective randomized factorial trial compared the thermal QST changes observed after a .05 mg/kg ketamine infusion or a saline placebo in chronic pain subjects who were either opioid-naive or were chronically using opioids for chronic noncancer pain are presented. No baseline QST differences were noted between the 4 groups at baseline. Comparison of changes preinfusion with postinfusion QST measurements resulted in decreased average change in temporal summation response between opioid subjects who received a placebo compared with those who received a ketamine infusion (-5.22, SD = 9.96 vs 13.81, SD = 19.55; P = .004). Additionally, the average change in temporal summation was decreased among subjects who received a ketamine infusion and were not chronically using opioids compared with subjects who were using chronic opioids and received a placebo infusion (-1.91, SD = 13.25 vs 13.81, SD = 19.55; P = .007). The results indicate that low-dose ketamine infusions produce subtle changes in QST phenotypes that are modified by the chronic use of opioids. This illustrates the potential diagnostic and therapeutic value of ketamine in the setting of chronic opioid use. ⋯ The presented data further our understanding of modulation of sensory perception in the setting of chronic opioid use and the role of the N-methyl-D-aspartate receptor. The use of low-dose ketamine infusions may be useful for the treatment as well as diagnosis of opioid-related neuropathic conditions.
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Review
Using Screening Tests to Predict Aberrant Use of Opioids in Chronic Pain Patients: Caveat Emptor.
Screening tests represent a critical tool in chronic pain treatment for predicting aberrant opioid use, which has emerged as a significant public health issue. Nevertheless, there remains a significant potential for the misapplication of screeners in this context. The potential difficulties in evaluating the diagnostic efficiency of screeners have been well established, particularly with regard to the effect that the prevalence of a disorder has on predictive value. ⋯ Given the prevalence of opioid problems, however, formulating clear clinical guidelines on such screeners appears highly important. The aims of the present report include: 1) providing a review of the salient issues necessary for interpreting diagnostic efficiency statistics of screening tests, 2) identifying the critical differences between sensitivity, specificity, and predictive value, and 3) discussing the characteristic effects that disease prevalence has on statistical prediction. The article also reviews key processes in screening measure development and highlights several key considerations relevant to their appropriate use in clinical decision-making.
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Weight loss is known to improve pain localized to weight-bearing joints but it is not known how weight loss affects the spatial distribution of pain and associated somatic symptoms like fatigue. We sought to determine if weight loss using a low-calorie diet improves pain, affect, and somatic symptoms commonly associated with chronic pain conditions in an observational study. We also documented changes in inflammatory markers in serum before and after weight loss. ⋯ Those who lost at least 10% of body weight showed greater improvement than those who lost <10%. Levels of the regulatory cytokine interleukin-10 increased after the intervention (P = .002). Weight loss may improve diffuse pain and comorbid symptoms commonly seen in chronic pain participants.