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Acute pancreatitis (AP) and recurring AP are serious health care problems causing excruciating pain and potentially lethal outcomes due to sepsis. The validated caerulein- (CAE) induced mouse model of acute/recurring AP produces secondary persistent hypersensitivity and anxiety-like behavioral changes for study.
Learn More >Migraine is one of the most common neurological diseases around the world and calcitonin gene-related peptide (CGRP) plays an important role in its pathophysiology. Therefore, in the present study, we evaluated the efficacy of monoclonal antibodies blocking the CGRP ligand or receptor in episodic and chronic migraine.
Learn More >Pruritus, commonly known as itch, is a very common symptom in numerous dermatological disorders and systemic diseases. It can manifest as acute, or when lasting longer than 6 weeks, it is considered chronic and can lead to significant distress and reduced quality-of-life of those suffering. Current therapeutics are limited and are lacking in efficacy, and the development of more effective treatments is needed. The neurokinin 1 receptor (NK1R) antagonists are a novel class of drugs that possess several properties such as antidepressant, anxiolytic and antiemetic activities. Recently, several studies have described the antipruritic activity of NK1R antagonists for treating chronic pruritus. In this review we outline the pathogenesis of chronic pruritus, the mechanism by which the neuropeptide substance P (SP) and its receptor NK1R may be targeted to inhibit pruritic activity, and the efficacy and tolerability of NK1R antagonists, which have been, or are currently being investigated for treating conditions where chronic pruritus is a major symptom. Increasing evidence from ongoing and completed studies demonstrates the importance of SP and NK1R signalling in mediating pruritic activity. Several NK1R antagonists have shown significant antipruritic activity and thus targeting the SP-NK1R pathway may provide a therapeutic option for treating chronic pruritus of certain origin/s in the foreseeable future.
Learn More >Affective-motivational disturbances are highly inconsistent in animal pain models. The reproducibility of the open-field test in assessing anxiety, malaise, or disability remains controversial despite its popularity. While traumatic, persistent, or multi-regional pain models are commonly considered more effective in inducing negative affect or functional impairment, the early psychobehavioral changes before pain chronification are often underexplored. Here, we aimed to clarify the fundamental relationship between hypernociception and passive distress-like behavior using a model of transient inflammatory pain. To minimize latent confounders and increase data consistency, male C57BL/6N mice were habituated to the open-field arena 6 times before receiving the unilateral intraplantar injection of prostaglandin E2 (PGE2) or vehicle. Open-field (40-minute exploration) and nociceptive behavior were evaluated repeatedly along the course of hypernociception in both wild-type and transgenic mice with a known pronociceptive phenotype. To reduce subjectivity, multivariate open-field behavioral outcomes were analyzed by statistical modeling based on exploratory factor analyses, which yielded a 2-factor solution. Within 3 hours after PGE2 injection, mice developed significantly reduced center exploration (factor 1) and a marginally significant increase in their habituation tendency (factor 2), which were not apparent in vehicle-injected mice. The behavioral passivity generally improved as hypernociception subsided. Therefore, transient inflammatory irritation is sufficient to suppress mouse open-field exploratory activity. The apparent absence of late affective-motivational changes in some rodents with prolonged hypernociception may not imply a lack of preceding or underlying neuropsychological alterations. Procedural pain after invasive animal experiments, however small, should be assessed and adequately controlled as a potential research confounder.
Learn More >There is a large body of research exploring what it means for a person to live with chronic pain. However, existing research does not help us understand what it means to recover. We aimed to identify qualitative research that explored the experience of living with chronic pain published since 2012 and to understand the process of recovery.
Learn More >Caregiving and other interpersonal interactions often require accurate perception of others' pain from nonverbal cues, but perceivers may be subject to systematic biases based on gender, race, and other contextual factors. Such biases could contribute to systematic under-recognition and under-treatment of pain. In two experiments, we studied the impact of perceived patient sex on lay perceivers' pain estimates and treatment recommendations. In Experiment 1 (N = 50), perceivers viewed facial video clips of female and male patients in chronic shoulder pain and estimated patients' pain intensity. Multi-level linear modeling revealed that perceivers under-estimated female patients' pain compared with male patients, after controlling for patients' self-reported pain and pain facial expressiveness. Experiment 2 (N = 200) replicated these findings, and additionally found that 1) perceivers' pain-related gender stereotypes, specifically beliefs about typical women's vs. men's willingness to express pain, predicted pain estimation biases; and 2) perceivers judged female patients as relatively more likely to benefit from psychotherapy, whereas male patients were judged to benefit more from pain medicine. In both experiments, the gender bias effect size was on average 2.45 points on a 0-100 pain scale. Gender biases in pain estimation may be an obstacle to effective pain care, and experimental approaches to characterizing biases, such as the one we tested here, could inform the development of interventions to reduce such biases. PERSPECTIVE: This study identifies a bias towards underestimation of pain in female patients, which is related to gender stereotypes. The findings suggest caregivers' or even clinicians' pain stereotypes are a potential target for intervention.
Learn More >Post-traumatic headache (PTH) consequent to mild traumatic brain injury (mTBI) is a complex, multidimensional, chronic neurological disorder. The purpose of this review is to evaluate the current neuroimaging studies on mTBI and PTH with a specific focus on brain networks and connectivity patterns.
Learn More >To identify correlates of quality of life (QoL) measured with the Quality of Life Scale (QOLS) in participants of a multidisciplinary day hospital treatment program for fibromyalgia (FM).
Learn More >Shifting microglial polarization from M1 toward M2 phenotype represents a promising therapeutic strategy for neuropathic pain (NP). Dual-specificity phosphatase-1 (DUSP1) is a key component in regulating anti-inflammatory response. The medial prefrontal cortex (mPFC) is implicated in emotional disorders associated with NP and constitutes a neuroanatomical substrate for exploring mechanisms underlying NP. This study aims to investigate whether DUSP1 regulates microglial M1/M2 polarization in the mPFC in a rat model of NP. Rat model of NP was established by chronic constriction injury (CCI) of the rat sciatic nerve. Lipopolysaccharide (LPS) was used to activate HAPI rat microglial cells as an inflammatory model. CCI-induced decreased pain threshold, increased cell apoptosis in mPFC, elevated pro-inflammatory M1/M2 microglia ratio, and activated MAPK signaling in the mPFC of rats. Importantly, intra-mPFC injection of DUSP1-expressing lentivirus counteracted these abnormalities. assay further confirmed that DUSP1 overexpression switched microglial M1 to M2 polarization through inhibition of MAPK signaling activation. DUSP1 switched microglial M1 to M2 polarization in the mPFC and attenuated CCI-induced NP by inhibiting the MAPK signaling.
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