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This study aims to study the effect of mindfulness-based program on the psychological, biomechanical and inflammatory domains of patients with chronic low back pain.
Learn More >Satellite glial cells (SGCs) of the dorsal root ganglia (DRG) ensure homeostasis and proportional excitability of sensory neurons and gained interest in the field of development and maintenance of neuropathic pain. Pigs represent a suitable species for translational medicine with a more similar anatomy and physiology to humans compared to rodents, and are used in research regarding treatment of neuropathic pain. Knowledge of anatomical and physiological features of porcine SGCs is prerequisite for interpreting potential alterations. However, state of knowledge is still limited. In the present study, light microscopy, ultrastructural analysis and immunofluorescence staining was performed. SGCs tightly surround DRG neurons with little vascularized connective tissue between SGC-neuron units, containing, among others, axons and Schwann cells. DRG were mainly composed of large sized neurons (∼59%), accompanied by fewer medium sized (∼36%) and small sized sensory neurons (∼6%). An increase of neuronal body size was concomitant with an increased number of surrounding SGCs. The majority of porcine SGCs expressed glutamine synthetase and inwardly rectifying potassium channel Kir 4.1, known as SGC-specific markers in other species. Similar to canine SGCs, marked numbers of porcine SGCs were immunopositive for glial fibrillary acidic protein, 2',3'-cyclic-nucleotide 3'-phosphodiesterase and the transcription factor Sox2. Low to moderate numbers of SGCs showed aquaporin 4-immunoreactivity (AQP4) as described for murine SGCs. AQP4-immunoreactivity was primarily found in SGCs ensheathing small and medium sized neuronal somata. Low numbers of SGCs were immunopositive for ionized calcium-binding adapter molecule 1, indicating a potential immune cell character. No immunoreactivity for common leukocyte antigen CD45 nor neural/glial antigen 2 was detected. The present study provides essential insights into the characteristic features of non-activated porcine SGCs, contributing to a better understanding of this cell population and its functional aspects. This will help to interpret possible changes that might occur under activating conditions such as pain.
Learn More >Itch and pain are common after burns. Neuropathic mechanisms may underlie both modalities but remain not well-understood. This study aims to prospectively document neuropathic pain symptoms and to identify potential itch symptom profiles that differ regarding duration and co-occurrence with neuropathic pain which may inform underlying pathophysiological mechanisms and respond to different treatments. Adult burn survivors ( = 192) self-reported itch and neuropathic pain at 2 weeks post-discharge, 3, 6, 12, and 18 months post-burn. Based on the presence of itch and pain symptoms over time, participants were allocated to one itch profile: transient itch/pain, chronic itch, or chronic & . Profiles were compared on itch over time using General Linear Modeling. Age, gender, burn severity, posttraumatic stress (PTS) symptoms and baseline itch intensity were examined as potential predictors of the profiles in a Multi-nominal regression analysis. Neuropathic pain occurred in 54% after discharge which decreased to 24% 18 months later. Itch intensity was highest in the chronic & profile. Compared to the transient itch profile, the chronic & profile was associated with higher burn severity and more PTS symptoms. Compared to the chronic itch profile, the chronic & profile was associated with more PTS symptoms. Findings suggest that biological and psycho-dermatological processes underlie both chronic neuropathic pain and itch processes in burn scars. Further research should elucidate the mechanisms underlying the different itch profiles, with specific focus on skin innervation and psychological factors.
Learn More >The magnitude of the cost of chronic pain has been a matter of concern in many countries worldwide. The high prevalence, the cost it implies for the health system, productivity, and absenteeism need to be addressed urgently. Studies have begun describing this problem in Chile, but there is still a debt in highlighting its importance and urgency on contributing to chronic pain financial coverage. This study objective is to estimate the expected cost of chronic pain and its related musculoskeletal diseases in the Chilean adult population. We conducted a mathematical decision model exercise, Markov Model, to estimate costs and consequences. Patients were classified into severe, moderate, and mild pain groups, restricted to five diseases: knee osteoarthritis, hip osteoarthritis, lower back pain, shoulder pain, and fibromyalgia. Data analysis considered a set of transition probabilities to estimate the total cost, sick leave payment, and productivity losses. Results show that the total annual cost for chronic pain in Chile is USD 943,413,490, corresponding an 80% to the five diseases studied. The highest costs are related to therapeutic management, followed by productivity losses and sick leave days. Low back pain and fibromyalgia are both the costlier chronic pain-related musculoskeletal diseases. We can conclude that the magnitude of the cost in our country's approach to chronic pain is related to increased productivity losses and sick leave payments. Incorporating actions to ensure access and financial coverage and new care strategies that reorganize care delivery to more integrated and comprehensive care could potentially impact costs in both patients and the health system. Finally, the impact of the COVID-19 pandemic will probably deepen even more this problem.
Learn More >Mas-related G protein-coupled receptor-X2 (MRGPRX2) expressed on mast cells (MCs) contributes to hypersensitivity reactions to cationic US-Food and Drug Administration (FDA) approved drugs such as the neuromuscular blocking agent, rocuronium. In addition, activation of MRGPRX2 by the neuropeptide substance P (SP) and the pro-adrenomedullin peptide (PAMP-12) is associated with a variety of cutaneous conditions such as neurogenic inflammation, pain, atopic dermatitis, urticaria, and itch. Thus, small molecules aimed at blocking MRGPRX2 constitute potential options for modulating IgE-independent MC-mediated disorders. Two inverse MRGPRX2 agonists, named C9 and C9-6, have recently been identified, which inhibit basal G protein activation and agonist-induced calcium mobilization in transfected HEK293 cells. Substance P serves as a balanced agonist for MRGPRX2 whereby it activates both G protein-mediated degranulation and β-arrestin-mediated receptor internalization. The purpose of this study was to determine if C9 blocks MRGPRX2's G protein and β-arrestin-mediated signaling and to determine its specificity. We found that C9, but not its inactive analog C7, inhibited degranulation in RBL-2H3 cells stably expressing MRGPRX2 in response to SP, PAMP-12 and rocuronium with an IC value of ~300 nM. C9 also inhibited degranulation as measured by cell surface expression of CD63, CD107a and β-hexosaminidase release in LAD2 cells and human skin-derived MCs in response to SP but not the anaphylatoxin, C3a or FcϵRI-aggregation. Furthermore, C9 inhibited β-arrestin recruitment and MRGPRX2 internalization in response to SP and PAMP-12. We found that a G protein-coupling defective missense MRGPRX2 variant (V282M) displays constitutive activity for β-arrestin recruitment, and that this response was significantly inhibited by C9. Rocuronium, SP and PAMP-12 caused degranulation in mouse peritoneal MCs and these responses were abolished in the absence of MrgprB2 or cells treated with pertussis toxin but C9 had no effect. These findings suggest that C9 could provide an important framework for developing novel therapeutic approaches for the treatment of IgE-independent MC-mediated drug hypersensitivity and cutaneous disorders.
Learn More >The anesthetic management of fetal operative procedures (FOP) is a highly debated topic. Literature on fetal pain perception and response to external stimuli is rapidly expanding. Nonetheless, there is no consensus on the fetal consciousness nor on the instruments to measure pain levels. As a result, no guidelines or clinical recommendations on anesthesia modality during FOP are available. This systematic literature review aimed to collect the available knowledge on the most common fetal interventions, and summarize the reported outcomes for each anesthetic approach. Additional aim was to provide an overall evaluation of the most commonly used anesthetic agents.
Learn More >Peripheral and central sensitizations of the trigeminal nervous system are the main mechanisms to promote the development and maintenance of chronic orofacial pain characterized by allodynia, hyperalgesia, and ectopic pain after trigeminal nerve injury or inflammation. Although the pathomechanisms of chronic orofacial pain are complex and not well known, sufficient clinical and preclinical evidence supports the contribution of the N-methyl-D-aspartate receptors (NMDARs, a subclass of ionotropic glutamate receptors) to the trigeminal nociceptive signal processing pathway under various pathological conditions. NMDARs not only have been implicated as a potential mediator of pain-related neuroplasticity in the peripheral nervous system (PNS) but also mediate excitatory synaptic transmission and synaptic plasticity in the central nervous system (CNS). In this review, we focus on the pivotal roles and mechanisms of NMDARs in the trigeminal nervous system under orofacial neuropathic and inflammatory pain. In particular, we summarize the types, components, and distribution of NMDARs in the trigeminal nervous system. Besides, we discuss the regulatory roles of neuron-nonneuronal cell/neuron-neuron communication mediated by NMDARs in the peripheral mechanisms of chronic orofacial pain following neuropathic injury and inflammation. Furthermore, we review the functional roles and mechanisms of NMDARs in the ascending and descending circuits under orofacial neuropathic and inflammatory pain conditions, which contribute to the central sensitization. These findings are not only relevant to understanding the underlying mechanisms, but also shed new light on the targeted therapy of chronic orofacial pain.
Learn More >Cranial autonomic symptoms (CAS), including conjunctival injection, tearing, nasal congestion or rhinorrhea, eyelid edema, miosis or ptosis, and forehead or facial sweating ipsilateral to headache, are often reported by patients with migraine during headache attacks. CAS is a consequence of the activation of the trigeminovascular system, which is the target of monoclonal antibodies acting on the CGRP pathway. Therefore, we hypothesized that patients with CAS might have higher trigeminovascular activation than those without CAS leading to a better response to anti-CGRP treatments.
Learn More >Chronic post-surgical pain (CPSP) is one of the adverse outcomes after surgery, especially in thoracotomy. However, the prevalence of CPSP in elderly adults (≥65 years), is still limited. Therefore, the present study was undertaken to establish and validate the prediction model of CPSP in those patients after thoracic surgery, including thoracotomy and video-assisted thoracoscopic surgery.
Learn More >Myriad psychosocial and cultural factors influence personal ways of coping with chronic pain (CP). Mobile health (mHealth) apps facilitate creation of citizen laboratories outside clinical frameworks. However, issues of safety, privacy and technostress must be addressed. This attitudinal user study aimed to assess whether persons with persistent pain (PwPP) would be open to sharing qualitative and quantitative data about their self-management of CP mHealth platforms.
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