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      Journal of Pain Research (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of high-quality laboratory and clinical findings in all fields of pain research and the prevention and management of pain. Sign up for email alerts here.

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      A Conceptual Model of Biopsychosocial Mechanisms of Transition from Acute to Chronic Postsurgical Pain in Children and Adolescents

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          Abstract

          Acute and chronic pain are highly prevalent and impactful consequences of surgery across the lifespan, yet a comprehensive conceptual model encompassing biopsychosocial factors underlying acute to chronic pain transition is lacking, particularly in youth. Building on prior chronic postsurgical pain models, we propose a new conceptual model of biopsychosocial mechanisms of transition from acute to chronic postsurgical pain. This review aims to summarize existing research examining key factors underlying acute to chronic postsurgical pain transition in order to guide prevention and intervention efforts aimed at addressing this health issue in children. As pain transitions from acute nociceptive pain to chronic pain, changes in the peripheral and central nervous system contribute to the chronification of pain after surgery. These changes include alterations in sensory pain processing and psychosocial processes (psychological, behavioral, and social components), which promote the development of chronic pain. Patient-related premorbid factors (eg, demographic factors, genetic profile, and medical factors such as premorbid pain) may further modulate these changes. Factors related to acute injury and recovery (eg, surgical and treatment factors), as well as biological response to surgery (eg, epigenetic, inflammatory, and endocrine factors), may also influence this process. Overall, longitudinal studies examining temporal pathways of biopsychosocial processes including both risk and resiliency factors will be essential to identify the mechanisms involved in the transition from acute to chronic pain. Research is also needed to unravel connections between the acute pain experience, opioid exposure, and sensory pain processing during acute to chronic pain transition. Furthermore, future studies should include larger and more diverse samples to more fully explore risk factors in a broader range of pediatric surgeries. The use of conceptual models to guide intervention approaches targeting mechanisms of transition from acute to chronic pain will significantly advance this field and improve outcomes for children and adolescents undergoing surgery.

          Most cited references78

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          Persistent postsurgical pain: risk factors and prevention.

          Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations, such as groin hernia repair, breast and thoracic surgery, leg amputation, and coronary artery bypass surgery. Since chronic pain can be severe in about 2-10% of these patients, persistent postsurgical pain represents a major, largely unrecognised clinical problem. Iatrogenic neuropathic pain is probably the most important cause of long-term postsurgical pain. Consequently, surgical techniques that avoid nerve damage should be applied whenever possible. Also, the effect of aggressive, early therapy for postoperative pain should be investigated, since the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state. Finally, the role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop chronic pain. Based on information about the molecular mechanisms that affect changes to the peripheral and central nervous system in neuropathic pain, several opportunities exist for multimodal pharmacological intervention. Here, we outline strategies for identification of patients at risk and for prevention and possible treatment of this important entity of chronic pain.
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            Genetic basis for individual variations in pain perception and the development of a chronic pain condition.

            Pain sensitivity varies substantially among humans. A significant part of the human population develops chronic pain conditions that are characterized by heightened pain sensitivity. We identified three genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase (COMT) that we designated as low pain sensitivity (LPS), average pain sensitivity (APS) and high pain sensitivity (HPS). We show that these haplotypes encompass 96% of the human population, and five combinations of these haplotypes are strongly associated (P=0.0004) with variation in the sensitivity to experimental pain. The presence of even a single LPS haplotype diminishes, by as much as 2.3 times, the risk of developing myogenous temporomandibular joint disorder (TMD), a common musculoskeletal pain condition. The LPS haplotype produces much higher levels of COMT enzymatic activity when compared with the APS or HPS haplotypes. Inhibition of COMT in the rat results in a profound increase in pain sensitivity. Thus, COMT activity substantially influences pain sensitivity, and the three major haplotypes determine COMT activity in humans that inversely correlates with pain sensitivity and the risk of developing TMD.
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              Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.

              Surgical and medical procedures, mainly those associated with nerve injuries, may lead to chronic persistent pain. Currently, one cannot predict which patients undergoing such procedures are 'at risk' to develop chronic pain. We hypothesized that the endogenous analgesia system is key to determining the pattern of handling noxious events, and therefore testing diffuse noxious inhibitory control (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain (CPTP). Pre-operative psychophysical tests, including DNIC assessment (pain reduction during exposure to another noxious stimulus at remote body area), were conducted in 62 patients, who were followed 29.0+/-16.9 weeks after thoracotomy. Logistic regression revealed that pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP. Efficient DNIC predicted lower risk of CPTP, with OR 0.52 (0.33-0.77 95% CI, p=0.0024), i.e., a 10-point numerical pain scale (NPS) reduction halves the chance to develop chronic pain. Higher acute pain intensity indicated OR of 1.80 (1.28-2.77, p=0.0024) predicting nearly a double chance to develop chronic pain for each 10-point increase. The other psychophysical measures, pain thresholds and supra-threshold pain magnitudes, did not predict CPTP. For prediction of acute post-operative pain intensity, DNIC efficiency was not found significant. Effectiveness of the endogenous analgesia system obtained at a pain-free state, therefore, seems to reflect the individual's ability to tackle noxious events, identifying patients 'at risk' to develop post-intervention chronic pain. Applying this diagnostic approach before procedures that might generate pain may allow individually tailored pain prevention and management, which may substantially reduce suffering.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                jpr
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                24 November 2020
                2020
                : 13
                : 3071-3080
                Affiliations
                [1 ]Department of Anesthesiology & Pain Medicine, University of Washington , Seattle, WA, USA
                [2 ]Center for Clinical and Translational Research, Seattle Children’s Hospital , Seattle, WA, USA
                [3 ]Center for Child Health, Behavior and Development, Seattle Children’s Hospital , Seattle, WA, USA
                [4 ]Department of Pediatrics, University of Washington , Seattle, WA, USA
                [5 ]Weill Cornell Medicine , New York, NY, USA
                Author notes
                Correspondence: Jennifer A Rabbitts Seattle Children’s Hospital , 4800 Sand Point Way NE MB.11.500.3, Seattle, WA98105, USATel +1 206-987-2704Fax +1 206-987-3935 Email jennifer.rabbitts@seattlechildrens.org
                Author information
                http://orcid.org/0000-0003-4800-1080
                http://orcid.org/0000-0001-6036-6715
                Article
                239320
                10.2147/JPR.S239320
                7699440
                33262642
                2f96921f-cd66-4314-b5f7-e576a8708347
                © 2020 Rabbitts et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 31 July 2020
                : 21 October 2020
                Page count
                Figures: 1, References: 78, Pages: 10
                Funding
                Funded by: National Institute of Arthritis;
                This work was supported by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases under Award No. R01AR073780 (Principal Investigator: Rabbitts, J.A.).
                Categories
                Review

                Anesthesiology & Pain management
                chronic postoperative pain,cpsp,neurobiological,risk factors,resilience,quantitative sensory testing

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