Pain after surgery in children: clinical recommendations

PURPOSE OF REVIEW: This article summarizes recent data related to the safety and efficacy of postoperative analgesia in children that influence clinical practice recommendations. RECENT FINDINGS: Postoperative pain continues to be experienced by hospitalized children and following discharge after short stay or ambulatory surgery. Updated recommendations for post-tonsillectomy analgesia exclude codeine and suggest regular administration of paracetamol and NSAID, but evidence for the most appropriate dose and type of opioid for rescue analgesia is limited. The incidence of opioid-related respiratory depression/oversedation in hospitalized children ranges from 0.11 to 0.41%, with recent large series identifying high-risk groups and contributory factors that can be targeted to minimize the risk of serious or permanent harm. Data demonstrating feasibility and safety of regional analgesic techniques is increasing, but additional and procedure-specific evidence would improve technique selection and inform discussions of efficacy and safety with patients and families/carers. Persistent postsurgical pain is increasingly recognized following major surgery in adolescents. Evaluation of potential predictive factors in clinical studies and investigation of underlying mechanisms in laboratory studies can identify targets for both pharmacological and nonpharmacological interventions. SUMMARY: Recommendations for postoperative pain in children continue to evolve, with data incorporated from randomized controlled trials, case series and large audits. Management of pain following surgery in children needs to not only encompass efficacy and safety in the immediate perioperative period, but also consider pain following discharge after ambulatory surgery and the potential risk of persistent postsurgical pain following major surgery

Developmental Mechanisms of CPSP: Clinical Observations and Translational Laboratory Evaluations

Understanding mechanisms that underly the transition from acute to chronic pain and identifying potential targets for preventing or minimizing this progression have specific relevance for chronic postsurgical pain (CPSP). Though it is clear that multiple psychosocial, family, and environmental factors may influence CPSP, this review will focus on parallels between clinical observations and translational laboratory studies investigating the acute and long-term effects of surgical injury on nociceptive pathways. This includes data related to alterations in sensitivity at different points along nociceptive pathways from the periphery to the brain; age- and sex-dependent mechanisms underlying the transition from acute to persistent pain; potential targets for preventive interventions; and the impact of prior surgical injury. Ongoing preclinical studies evaluating age- and sex-dependent mechanisms will also inform comparative efficacy and preclinical safety assessments of potential preventive pharmacological interventions aimed at reducing the risk of CPSP. In future clinical studies, more detailed and longitudinal peri-operative phenotyping with patient- and parent-reported chronic pain core outcomes, alongside more specialized evaluations of somatosensory function, modulation, and circuitry, may enhance understanding of individual variability in postsurgical pain trajectories and improve recognition and management of CPSP

Neuropathic pain in children: Steps towards improved recognition and management

Neuropathic pain in children can be severe and persistent, difficult to recognise and manage, and associated with significant pain-related disability. Recognition based on clinical history and sensory descriptors is challenging in young children, and screening tools require further validation at older ages. Confirmatory tests can identify the disease or lesion of the somatosensory nervous system resulting in neuropathic pain, but feasibility and interpretation may be influenced by age- and sex-dependent changes throughout development. Quantitative sensory testing identifies specific mechanism-related sensory profiles; brain imaging is a potential biomarker of alterations in central processing and modulation of both sensory and affective components of pain; and genetic analysis can reveal known and new causes of neuropathic pain. Alongside existing patient- and parent-reported outcome measures, somatosensory system research methodologies and validation of mechanism-based standardised end-points may inform individualised therapy and stratification for clinical trials that will improve evidence-based management of neuropathic pain in children

Neuropathic pain in children

Lesions or disease of the somatosensory nervous system can produce neuropathic pain (NP). Typical features include spontaneous or paroxysmal pain, often described as burning, shooting, like electric shocks, or pins and needles. NP does occur in childhood, but age at the time of injury may influence the risk of NP following traumatic nerve injuries. Whilst conditions commonly associated with NP in adults may be less common in childhood (e.g., trigeminal neuralgia), other conditions (e.g., Fabry’s disease and erythromelalgia) may present with pain in childhood and provide a diagnostic challenge for paediatric practitioners

Persistent changes in peripheral and spinal nociceptive processing after early tissue injury

It has become clear that tissue damage during a critical period of early life can result in long-term changes in pain sensitivity, but the underlying mechanisms remain to be fully elucidated. Here we review the clinical and preclinical evidence for persistent alterations in nociceptive processing following neonatal tissue injury, which collectively point to the existence of both a widespread hypoalgesia at baseline as well as an exacerbated degree of hyperalgesia following a subsequent insult to the same somatotopic region. We also highlight recent work investigating the effects of early trauma on the organization and function of ascending pain pathways at a cellular and molecular level. These effects of neonatal injury include altered ion channel expression in both primary afferent and spinal cord neurons, shifts in the balance between synaptic excitation and inhibition within the superficial dorsal horn (SDH) network, and a ‘priming’ of microglial responses in the adult SDH. A better understanding of how early tissue damage influences the maturation of nociceptive circuits could yield new insight into strategies to minimize the long-term consequences of essential, but invasive, medical procedures on the developing somatosensory system

Intravenous opioids for chemotherapy-induced severe mucositis pain in children: Systematic review and single-center case series of management with patient- or nurse-controlled analgesia (PCA/NCA)

BACKGROUND: Chemotherapy-induced oral mucositis can result in severe pain. Intravenous (IV) opioids are recommended, but management protocols vary. We systematically reviewed studies reporting IV opioid use for pain related to chemotherapy-induced severe oral mucositis in children and conducted a large single-center case series. METHODS: Ovid MEDLINE, PubMed, and Cochrane databases were searched for studies reporting IV opioid duration and/or dose requirements for severe mucositis. Secondly, our pain service database was interrogated to describe episodes of opioid administration by patient- or nurse-controlled analgesia (PCA/NCA) for children with mucositis and cancer treatment-related pain. RESULTS: Seventeen studies (six randomized trials, two prospective observational, three retrospective cohort, six retrospective case series) included IV opioid in 618 patients (age 0.3–22.3 years), but reported parameters varied. Mucositis severity and chemotherapy indication influenced IV opioid requirements, with duration ranging from 3 to 68 days and variable dose trajectories (hourly morphine or equivalent 0-97 mcg/kg/h). Our 7-year series included PCA/NCA for 364 episodes of severe mucositis (302 patients; age 0.12–17.2 years). Duration ranged from 1 to 107 days and dose requirements in the first 3 days from 1 to 110 mcg/kg/h morphine. Longer PCA/NCA duration was associated with: higher initial morphine requirements (ρ = 0.46 [95% CI 0.35, 0.57]); subsequent increased pain and need for ketamine co-analgesia (118/364 episodes with opioid/ketamine 13.9 [9.8–22.2] days vs opioid alone 6.0 [3.9–10.8] days; median [IQR]); but not with age or sex. CONCLUSIONS: Management of severe mucositis pain can require prolonged IV opioid therapy. Individual and treatment-related variability in analgesic requirements highlight the need for regular review, titration, and management by specialist services

Breast cancer in young women: prevalence of LOH at p53, BRCA1 and BRCA2

Breast cancer in young women: prevalance of LOH at p53, BRCA1 and BRCA

Motor output and control input in flapping flight: a compact model of the deforming wing kinematics of manoeuvring hoverflies

Insects are conventionally modelled as controlling flight by varying a few summary kinematic parameters that are defined on a per-wingbeat basis, such as the stroke amplitude, mean stroke angle and mean wing pitch angle. Nevertheless, as insects have tens of flight muscles and vary their kinematics continuously, the true dimension of their control input space is likely to be much higher. Here, we present a compact description of the deforming wing kinematics of 36 manoeuvring Eristalis hoverflies, applying functional principal components analysis to Fourier series fits of the wingtip position and wing twist measured over 26 541 wingbeats. This analysis offers a high degree of data reduction, in addition to insight into the natural kinematic couplings. We used statistical resampling techniques to verify that the principal components (PCs) were repeatable features of the data, and analysed their coefficient vectors to provide insight into the form of these natural couplings. Conceptually, the dominant PCs provide a natural set of control input variables that span the control input subspace utilized by this species, but they can also be thought of as output states of the flight motor. This functional description of the wing kinematics is appropriate to modelling insect flight as a form of limit cycle control