Browse by Audience
Severe neuropathic pain is a hallmark of Fabry disease, a genetic disorder caused by a deficiency in lysosomal α-Galactosidase A. Pain experienced by these patients significantly impacts their quality of life and ability to perform everyday tasks. Fabry patients suffer from peripheral neuropathy, sensory abnormalities, acute pain crises, and lifelong ongoing pain. Although treatment of pain through medication and enzyme replacement therapy (ERT) exists, pain persists in many of these patients. Some has been learned in the past decades regarding clinical manifestations of pain in Fabry disease and the pathological effects of α-Galactosidase A insufficiency in neurons. Still, it is unclear how pain and sensory abnormalities arise in Fabry patients and how these can be targeted with therapeutics. Our knowledge is limited in part due to the lack of adequate preclinical models to study the disease. This review will detail the types of pain, sensory abnormalities, influence of demographics on pain, and current strategies to treat pain experienced by Fabry patients. In addition, we discuss the current knowledge of Fabry pain pathogenesis and which aspects of the disease preclinical models accurately recapitulate. Understanding the commonalities and divergences between humans and preclinical models can be utilized to further interrogate mechanisms causing the pain and sensory abnormalities as well as advance development of the next generation of therapeutics to treat pain in Fabry patients.
Learn More >It has been proposed that Complex Regional Pain Syndrome (CRPS) is a post-traumatic autoimmune disease. Previously we observed that B cells contribute to CRPS-like changes in a mouse tibia fracture model, and that early (< 12 months duration) CRPS patient IgM antibodies have pronociceptive effects in the skin and spinal cord of muMT fracture mice lacking B cells. The current study evaluated the pronociceptive effects of intraplantar or intrathecal injections of early CRPS IgM (5ug) in muMT fracture mice. Skin and lumbar spinal cord were collected for immunohistochemistry and polymerase chain reaction (PCR) analyses. Wildtype mice exhibited post fracture increases in complement component C5a and its receptor expression in skin and spinal cord, predominantly on dermal macrophages and spinal microglia. Intraplantar IgM injection caused nociceptive sensitization in muMT fracture mice with increased complement component C1q and inflammatory cytokine expression, and these IgM effects were blocked by a C5a receptor antagonist (PMX53) or a global cytokine inhibitor (pentoxifylline). Intrathecal IgM injection also had pronociceptive effects with increased spinal cytokine expression, effects that were blocked by PMX53 or pentoxifylline treatment. Intrathecal injection of chronic (> 12 months duration) CRPS patient IgM (but not IgG) caused nociceptive sensitization in muMT fracture mice, but intraplantar injection of chronic CRPS IgM or IgG had no effect. We postulate that CRPS IgM antibodies bind to neoantigens in the fracture limb skin and corresponding spinal cord to activate C5a complement signaling in macrophages and microglia, evoking proinflammatory cytokine expression contributing to nociceptive sensitization in the injured limb.
Learn More >Early life abuse (ELAb) initiates pathophysiological cascades resulting in long-term maladaptive stress responsivity, hyperalgesia and an increased risk for psychopathology. Mindfulness-based stress reduction (MBSR) is effective in modifying psychological and somatic symptoms; thus, we predicted that MBSR would be particularly efficacious for women with ELAb.
Learn More >More than 750,000 people in the United States died from an overdose between 1999 and 2018; two-thirds of those deaths involved an opioid. In this review, we present trends in opioid overdose rates during this period and discuss how the proliferation of opioid prescribing to treat chronic pain, changes in the heroin and illegally manufactured opioid synthetics markets, and social factors, including deindustrialization and concentrated poverty, contributed to the rise of the overdose epidemic. We also examine how current policies implemented to address the overdose epidemic may have contributed to reducing prescription opioid overdoses but increased overdoses involving illegal opioids. Finally, we identify new directions for research to understand the causes and solutions to this critical public health problem, including research on heterogeneous policy effects across social groups, effective approaches to reduce overdoses of illegal opioids, and the role of social contexts in shaping policy implementation and impact. Expected final online publication date for the , Volume 42 is April 1, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Learn More >Inflammatory pain activates astrocytes and increases inflammatory cytokine release in the spinal cord. Mitochondrial fusion and fission rely on the functions of dynamin-related protein 1 (Drp1) and optic atrophy 1 (OPA1), which are essential for the synaptic transmission and plasticity. In the present study, we aimed to explore the effects of 2-bromopalmitate (2-BP), an inhibitor of protein palmitoylation, on the modulation of pain behavior. Rats were intraplantar injected with complete Freund's adjuvant (CFA) to establish an inflammatory pain model. In the spinal cord of rats with CFA-induced inflammatory pain, the expression of astrocyte-specific glial fibrillary acidic protein (GFAP) and contents of proinflammatory cytokines IL-1β and TNF-α were increased. Mitochondrial Drp1 was increased, while OPA1 was decreased. Consequently, CFA induced reactive oxygen species (ROS) production and Bcl-2-associated X protein (BAX) expression. The intrathecal administration of 2-BP significantly reversed the pain behaviors of the inflammatory pain in rats. Moreover, 2-BP also reduced the Drp1 expression, elevated the OPA1 expression, and further reduced the GFAP, IL-1β, and TNF-α expression and ROS production. Furthermore, in vitro study proved a similar effect of 2-BP on the regulation of Drp1 and OPA1 expression. 2-BP also increased the mitochondrial membrane potential and decreased the levels of BAX, ROS, and proinflammatory cytokines. These results indicate that 2-BP may attenuate the inflammatory pain of CFA-treated rats via regulating mitochondrial fission/fusion balance and function.
Learn More >Based on associative learning theories it is hypothesised that pain might be a conditioned response. In people with musculoskeletal pain, the occurrence of movement-induced pain might be a protective response, influenced by visual cues suggesting that the person is approaching a painful position. This study aimed to determine (1) whether pain-free range of motion (ROM) increased and decreased when visual feedback understated or overstated true rotation in people with neck pain and (2) whether this effect was more pronounced if pain was chronic.
Learn More >Current analgesic treatments for phantom pain are not optimal. One well-accepted yet limited nonpharmacological option is mirror therapy, which is thought to counterbalance abnormal plasticity. Transcranial direct current stimulation (tDCS) is an emerging approach believed to affect the membrane potential and activity threshold of cortical neurons. tDCS analgesic effectiveness, however, is mild and short, rendering it a noneffective stand-alone treatment. This study aimed to assess if a combination of mirror therapy with tDCS results in a superior analgesic effect as compared with mirror therapy alone in patients suffering from phantom pain due to recent amputation.
Learn More >Identifying biomarkers is a priority in translational chronic pain research. Dehydroepiandrosterone (DHEA) and its sulfated form, DHEA-S, are adrenocortical steroids in the blood with neuroprotective properties that also produce sex hormones. They may capture key sex-specific neuroendocrine mechanisms of chronic pain.
Learn More >Multisite pain remains significantly understudied following lower-limb loss (LLL), especially among females. This study aimed to explore sex-specific differences in the presentation of multisite pain post-LLL. Hypotheses were multisite pain would be more prevalent among females post-LLL as compared to males, and female sex would be significantly associated with multisite pain prevalence.
Learn More >To propose a new model outlining a hypothesized cyclical relation between executive functioning, emotional regulation, and chronic pain in adolescence and to highlight the likely importance of such a relation for self-management behavior and pain-related disability.
Learn More >