Pain
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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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Postoperative pain management continues to be suboptimal because of the lack of effective nonopioid therapies and absence of understanding of sex-driven differences. Here, we asked how the NLRP3 inflammasome contributes to postoperative pain. Inflammasomes are mediators of the innate immune system that are responsible for activation and secretion of IL-1β upon stimulation by specific molecular signals. ⋯ Sensory neuron-specific deletion of NLRP3 revealed that in males, NLRP3 expressed in non-neuronal cells and potentially sensory neurons drives postoperative pain. However, in females, only the NLRP3 that may be expressed in sensory neurons contributes to postoperative pain where the non-neuronal cell contribution is NLRP3 independent. This is the first evidence of a key role for NLRP3 in postoperative pain and reveals immune-mediated sex differences in postoperative pain.