Pain
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Randomized Controlled Trial
Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy: a randomized, placebo-controlled, crossover study.
Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of α2δ subunits of voltage-gated Ca channels, such as pregabalin, have shown efficacy in reducing mechanical sensitivity in animal models of neuropathic pain. In addition, some data suggest that pregabalin may be more efficacious in relieving neuropathic pain in subjects with increased sensitivity to pinprick. ⋯ There was no significant difference between pregabalin and placebo in reducing average daily pain (22.5% vs 10.7%, P = 0.23) or worst pain (29.2% vs 16.0%, P = 0.13) from baseline. Post hoc analysis of patients with CIPN caused by oxaliplatin (n = 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% vs 14.6%, P = 0.04). In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN.
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Meta Analysis
Pharmacological interventions for chronic pain in children: an overview of systematic reviews.
We know little about the safety or efficacy of pharmacological medicines for children and adolescents with chronic pain, despite their common use. Our aim was to conduct an overview review of systematic reviews of pharmacological interventions that purport to reduce pain in children with chronic noncancer pain (CNCP) or chronic cancer-related pain (CCRP). We searched the Cochrane Database of Systematic Reviews, Medline, EMBASE, and DARE for systematic reviews from inception to March 2018. ⋯ Overall, the quality of evidence was very low, and we have very little confidence in the effect estimates. The state of evidence of randomized controlled trials in this field is poor; we have no evidence from randomised controlled trials for pharmacological interventions in children with cancer-related pain, yet cannot deny individual children access to potential pain relief. Prospero ID: CRD42018086900.
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Although chronic postsurgical pain (CPSP) is a major health care problem, pain-related functional interference has rarely been investigated. Using the PAIN OUT registry, we evaluated patients' pain-related outcomes on the first postoperative day, and their pain-related interference with daily living (Brief Pain Inventory) and neuropathic symptoms (DN4: douleur neuropathique en 4 questions) at 6 months after surgery. Endpoints were pain interference total scores (PITS) and their association with pain and DN4 scores. ⋯ Preexisting chronic pain (3.6 [2.6-5.1]; P < 0.001), time spent in severe acute pain (2.9 [1.3-6.4]; P = 0.008), neurosurgical back surgery in males (3.6 [1.7-7.6]; P < 0.001), and orthopedic surgery in females (1.7 [1.0-3.0]; P = 0.036) were the variables with strongest association with PITS. Pain interference total scores might provide more precise information about patients' outcomes than pain scores only. Because neuropathic symptoms increase PITS, a suitable instrument for their routine assessment should be defined.
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Children who develop greater negatively-biased recall of pain (ie, recalled pain is higher than the initial pain report) following surgery are at risk for developing chronic pain; therefore, identifying risk factors for the development of biased pain memories is important. Higher anxiety has been implicated in the development of greater negatively-biased recall of pain; however, studies have not examined anxiety at multiple time points before and after a surgery and its relationship to children's postsurgical pain memories after 1 year. This prospective study examined a cohort of 237 children and adolescents undergoing major surgery. ⋯ Specifically, higher anxiety sensitivity at baseline and greater tendencies to catastrophize about pain at baseline and in the immediate acute recovery phase were most strongly linked to greater negatively-biased recall of pain. Greater negatively-biased recall of pain was related to higher pain intensity at 6 and 12 months post surgery. Findings support conceptual models of anxiety and pain memory biases and can inform intervention efforts to reduce anxiety in the pre- and post-op periods to minimize negative biases in pain memories.
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Genetics studies on the placebo hypoalgesic effect highlight a promising link between single nucleotide polymorphisms (SNPs) in the dopamine, opioid, and endocannabinoid genes and placebo hypoalgesia. However, epistasis and replication studies are missing. In this study, we expanded on previous findings related to the 3 SNPs in the opioid receptor mu subunit (OPRM1 rs1799971), catechol-O-methyltransferase (COMT rs4680), and fatty acid amide hydrolase (FAAH rs324420) genes associated with placebo hypoalgesia and tested the effect of a 3-way interaction on placebo hypoalgesia. ⋯ Finally, the model that included the placebo procedure and genotypes predicted placebo responsiveness with a higher accuracy (area under the curve, AUC = 0.773) as compared to the SNPs alone indicating that genetic variants can only partially explain the placebo responder status. Our results suggest that the endogenous mu-opioid system with a larger activation in response to pain in the met/val allele carriers as well as the synergism between endogenous mu-opioid system and cannabinoids might play the most relevant role in driving hypoalgesic responses. Future epistasis studies with larger sample sizes will help us to fully understand the complexity of placebo effects and explain the mechanisms that underlie placebo responsiveness.