Browse by Audience
Fabry disease belongs to lysosomal storage disorders and can be successfully treated today. On the contrary, the correct diagnostic classification of its symptoms can be challenging and most patients suffer from pain for years, until they are diagnosed correctly. The aim of this project was to characterize patients with unclassified extremity pain and to present a simple algorithm for a retrospective stratification approach.
Learn More >Diagnostic criteria for fibromyalgia have been subject to debate and controversy for many years. The preliminary diagnostic criteria introduced in 2010 and 2011 have been criticized for different reasons, including questionable diagnostic specificity and a lack of an etiopathogenetic foundation. The "ABC indicators" presented in this study reflect a further development of the 2011 criteria and refer to (A) algesia, (B) bilateral, axial-symmetric pain distribution, and (C) chronic distress.
Learn More >Opioids play a major role at descending pain modulation but the effects of neuropathic pain on the brain opioidergic system remain understudied. Since descending facilitation is enhanced during neuropathic pain, we studied the opioidergic modulation of the dorsal reticular nucleus (DRt), a medullary pain facilitatory area, in the spared nerve injury (SNI) model of neuropathic pain. We first performed a series of behavioral experiments in naïve-animals to establish the role of μ-opioid receptor (MOR) in the effects of endogenous and exogenous opioids at the DRt. Specifically, we showed that lentiviral-mediated MOR-knockdown at the DRt increased sensitivity to thermal and mechanical stimuli while the MOR agonist DAMGO induced the opposite effects. Additionally, we showed that MOR-knockdown and the pharmacological blockade of MOR by CTAP at the DRt decreased and inhibited, respectively, the analgesic effects of systemic morphine. Then, we performed microdialysis to measure enkephalin peptides in the DRt and evaluated MOR expression in the DRt at mRNA, protein and phosphorylated form levels by quantitative real-time PCR and immunohistochemistry, respectively. SNI-animals, compared to sham control, showed higher levels of enkephalin peptides, lower MOR-labeled cells without alterations in MOR mRNA levels, and higher phosphorylated MOR-labeled cells. Finally, we performed behavioral studies in SNI animals to determine the potency of systemic morphine and the effects of the pharmacologic and genetic manipulation of MOR at the DRt. We showed a reduced potency of the antiallodynic effects of systemic morphine in SNI-animals compared to the antinociceptive effects in sham animals. Increasing MOR-cells at the DRt of SNI-animals by lentiviral-mediated MOR-overexpression produced no effects on mechanical allodynia. DAMGO induced anti-allodynia only after MOR-overexpression. These results show that MOR inhibits DRt pain facilitatory actions and that this action contributes to the analgesic effects of systemic opioids. We further show that the inhibitory function of MOR is impaired during neuropathic pain. This is likely due to desensitization and degradation of MOR which are adaptations of the receptor that can be triggered by MOR phosphorylation. Skipping counter-regulatory pathways involved in MOR adaptations might restore the opioidergic inhibition at pain facilitatory areas.
Learn More >Persistent post-surgical pain (PPSP) is a common condition following surgery, resulting in persistent pain and reduced quality of life (QoL). While pharmacological management is common, its effectiveness remains equivocal. This systematic review investigated the effectiveness of physiotherapy management in adults with PPSP in comparison to usual care.
Learn More >The traditional analgesics used to treat neuropathic pain such as anticonvulsants, opioids, and nonsteroidal anti-inflammatory drugs (NSAIDs) lack efficacy and/or carry unpleasant side effects. The present study aimed to investigate the synergistic antinociceptive effects of co-administered low doses of ibuprofen and dexamethasone in rats with trigeminal neuropathic pain.
Learn More >Juvenile Idiopathic Arthritis (JIA) is the most common rheumatic disease in childhood, with chronic pain being a main symptom. JIA symptoms can lead to substantial disability in children and their families. While preliminary evidence reveals the potential beneficial role of resilience in dealing with chronic pain, research on the role of resilience in how families of a child with JIA cope with pain-related symptoms is scant and dispersed. Using the framework of the Ecological Resilience-Risk Model, this review aims to identify (1) family characteristics that are associated with both risk and resilience in children with JIA and (2) the contribution of individual and parental resilience mechanisms and resources to resilience outcomes in children with JIA and their families. MEDLINE, EMBASE, EBSCO, Psycharticles, and PsycINFO were systematically searched. Longitudinal, cross-sectional, and treatment studies written in English with a focus on resilience resources and/or mechanisms in families of a child (6-18 years) with JIA were included. The original search (July 2016) produced 415 articles, with a final sample of 6 articles remaining after screening. An updated search (July 2018) did not identify new articles, but identified one extra article through personal communications. The 7 articles were included in a narrative review and study quality was assessed. Limited research was available on the role of family characteristics, with just one study revealing how family dysfunction is related to reduced child resilience. Studies evaluating the role of individual resilience mechanisms and resources most commonly assessed resilience outcomes in terms of recovery and sustainability outcomes, such as health-related quality of life (HRQL) and functional disability. The findings revealed that children's psychological flexibility, self-efficacy, adherence, pain acceptance, and perceived social support contribute to resilience outcomes. Findings were inconclusive for the influence of coping strategies, such as seeking social support. While our knowledge is growing, a better understanding of how familial and individual resilience resources and mechanisms influence adjustment to chronic pain as part of JIA is needed and can stimulate development of targeted interventions to enhance outcomes for children with JIA.
Learn More >Data on clinical presentation of Hemiplegic Migraine (HM) are quite limited in the literature, particularly in the pediatric age. The aim of the present study is to describe in detail the phenotypic features at onset and during the first years of disease of sporadic (SHM) and familial (FHM) pediatric hemiplegic migraine and to review the pertinent literature. Retrospective study of a cohort of children and adolescents diagnosed with hemiplegic migraine, recruited from 11 Italian specialized Juvenile Headache Centers. Forty-six cases (24 females) were collected and divided in two subgroups: 32 SHM (16 females), 14 FHM (8 females). Mean age at onset was 10.5 ± 3.8 y (range: 2-16 y). Mean duration of motor aura was 3.5 h (range: 5 min-48 h). SHM cases experienced more prolonged attacks than FHM cases, with significantly longer duration of both motor aura and of total HM attack. Sensory (65%) and basilar-type auras (63%) were frequently associated to the motor aura, without significant differences between SHM and FHM. At follow-up (mean duration 4.4 years) the mean frequency of attacks was 2.2 per year in the first year after disease onset, higher in FHM than in SHM cases (3.9 vs. 1.5 per year, respectively). A literature review retrieved seven studies, all but one were based on mixed adults and children cohorts. This study represents the first Italian pediatric series of HM ever reported, including both FHM and SHM patients. Our cohort highlights that in the pediatric HM has an heterogeneous clinical onset. Children present fewer non-motor auras as compared to adults and in some cases the first attack is preceded by transient neurological signs and symptoms in early childhood. In SHM cases, attacks were less frequent but more severe and prolonged, while FHM patients had less intense but more frequent attacks and a longer phase of active disease. Differently from previous studies, the majority of our cases, even with early onset and severe attacks, had a favorable clinical evolution.
Learn More >Predicting who will be a placebo responder is a prerequisite to maximize placebo effects in pain treatment and to minimize them in clinical trials. First evidence exists that genetics could affect placebo effects. However, a classical twin study to estimate the relative contribution of genetic influences compared to common and individual environmental influences in explaining interindividual differences in placebo responsiveness has yet not been performed. In a first explorative twin study, 25 monozygotic (MZ) and 14 dizygotic (DZ) healthy twin pairs (27.5 ± 7.7 years; 73% female) were conditioned to the efficacy of a placebo analgesic ointment with an established heat pain paradigm on their non-dominant arm. Placebo analgesia was then tested on their dominant arm. Furthermore, warmth detection thresholds (WDTs) and heat pain thresholds (HPTs) were assessed, and participants filled in questionnaires for the assessment of psychological traits such as depression, anxiety, optimism, pain catastrophizing, and sensitivity to reward and punishment. Their expectations were determined with a visual analog scale. There was a small but significant placebo analgesic effect in both MZ and DZ twins. Estimates of heritability were moderate for WDT only but negligible for HPT, the conditioning response, and placebo analgesia. Common environment did not explain any variance, and the individual environment explained the largest parts. Therefore, the placebo analgesia response can be seen as influenced by individual learning experiences during the conditioning procedure, whereas other variables assessed were not associated. Compared to the individual learning experience, genetic influences seem to play a minor role in explaining variation in placebo analgesia in this experimental paradigm. However, our results are restricted to placebo effects through conditioning on pain in healthy volunteers and should be replicated in larger samples and in patients. Furthermore, potential gene-environment interactions should be further investigated.
Learn More >Exposure (EXP) is a cognitive-behavioral treatment aimed at reducing pain-related fear in chronic pain, and has proven successful in reducing pain-related disability in patients with chronic low back pain (cLBP). The current longitudinal study aimed to reveal the neural correlates of changes in pain-related fear as a result of EXP. Twenty-three patients with cLBP were included in this study. Patients with cLBP underwent MRI scanning pre-treatment (pre-EXP), post-treatment (post-EXP), and 6 months after end of treatment (FU-EXP). Pain-free controls were scanned at two time points. In the scanner, participants were presented with pictures involving back-related movements, evoking pain-related fear in patients. Pre-treatment, functional MRI revealed increased activation in right posterior insula and increased deactivation in medial prefrontal cortex (mPFC) in patients compared to controls. Post-treatment, patients reported reduced fear and pre-EXP group differences were no longer present. Contrasting pre- to post- and FU-EXP in patients revealed that stimulus-evoked neural responses changed in sensorimotor as well as cognitive/affective brain regions. Lastly, exploratory analyses revealed a tendency toward an association between changes in neural activation and changes in fear ratings, including the hippocampus and temporal lobe (pre- to post-EXP changes), and mPFC and posterior cingulate cortex (pre- to FU-EXP changes). Taken together, we show evidence that neural circuitry for pain-related fear is modulated by EXP, and that changes are associated with self-reported decreases in pain-related fear.
Learn More >Chronic pain is associated with decreased quality of life and is one of the most common reasons adults seek medical care, making treatment imperative for many aspects of patient well-being. Chronic pain management typically involves the use of Schedule II full μ-opioid receptor agonists for pain relief; however, the increasing prevalence of opioid addiction is a national crisis that is impacting public health and social and economic welfare. Buprenorphine is a Schedule III partial μ-opioid receptor agonist that is an equally effective but potentially safer treatment option for chronic pain than full μ-opioid receptor agonists. The purpose of this review is to provide an overview of the clinical efficacy and safety of the transdermal and buccal formulations of buprenorphine, which are approved by the Food and Drug Administration for chronic pain, compared with that of extended-release full μ-opioid receptor agonists.
Learn More >