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BACKGROUND: The Acapella is a respiratory rehabilitation device designed to aid sputum clearance. When the patient exhales through this device, continuous and oscillatory pressure levels are produced. The adequate practical use of the Acapella is critically dependent on the characteristics of the produced pressure, which include the production of a mean pressure c=:: 10 cm H20 and a matching of the oscillation frequency with the respiratory-system resonance frequency, and/or with the frequency of ciliary movement (approximately 13 Hz). The development of a dedicated software tool would contribute to optimize the clinical application of this device. Thus, the aim of this study was 2-fold: to characterize the mechanical behavior of the Acapella, and to develop a software tool to ease the practical use of this device. METHODS: An experimental setup was assembled in order to study mean pressure, oscillation frequency, and the oscillation amplitudes produced by 3 Acapella devices (model green) in the whole range of instrument adjustments and under air flow rates ranging from 200 mL/s to 800 mL/s. In order to increase flexibility, allowing the fast integration of further information obtained in future studies, the software was developed in a graphical environment. RESULTS: The device characterization showed an oscillation frequency varying from 8 Hz to 21 Hz, mean pressure ranging from 3 cm H20 to 23 cm H20, and oscillation amplitude from 4 cm H20 to 9 cm H20. These parameters increased with flow and instrument adjustment. A user-friendly software was developed, incorporating the current knowledge concerning secretion removal. After the introduction of the desired frequency and the patient air flow by the user, the software automatically calculates the necessary instrument adjustment, as well as mean pressure and oscillation amplitude. CONCLUSIONS: The Acapella device may produce clinically adequate values of mean pressure and oscillation frequency. However, it depends on its use at optimized conditions. The user-friendly software proposed in this study could help the user to achieve these conditions. [ABSTRACT FROM AUTHOR]

Cytotoxic agents synergize with immune checkpoint inhibitors and improve outcomes for patients with several cancer types. Nonetheless, a parallel increase in the incidence of dose-limiting side effects, such as peripheral neuropathy, is often observed. Here, we investigated the role of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis in the modulation of paclitaxel-induced neuropathic pain. We found that human and mouse neural tissues, including the dorsal root ganglion (DRG), expressed basal levels of PD-1 and PD-L1. During the development of paclitaxel-induced neuropathy, an increase in PD-L1 expression was observed in macrophages from the DRG. This effect depended on Toll-like receptor 4 activation by paclitaxel. Furthermore, PD-L1 inhibited pain behavior triggered by paclitaxel or formalin in mice, suggesting that PD-1/PD-L1 signaling attenuates peripheral neuropathy development. Consistent with this, we observed that the combined use of anti-PD-L1 plus paclitaxel increased mechanical allodynia and chronic neuropathy development induced by single agents. This effect was associated with higher expression of inflammatory markers (Tnf, Il6, and Cx3cr1) in peripheral nervous tissue. Together, these results suggest that PD-1/PD-L1 inhibitors enhance paclitaxel-induced neuropathic pain by suppressing PD-1/PD-L1 antinociceptive signaling., (©2022 American Association for Cancer Research.)

Chemotherapy-induced peripheral neuropathy (CIPN) is the main dose-limiting adverse effect of chemotherapy drugs such as paclitaxel (PTX). PTX causes marked molecular and cellular damage, mainly in the peripheral nervous system, including sensory neurons in the dorsal root ganglia (DRG). Several studies have shown the therapeutic potential of cannabinoids, including cannabidiol (CBD), the major non-psychotomimetic compound found in the Cannabis plant, to treat peripheral neuropathies. Here, we investigated the efficacy of PECS-101 (former HUF-101), a CBD fluorinated analog, on PTX-induced neuropathic pain in mice. PECS-101, administered after the end of treatment with PTX, did not reverse mechanical allodynia. However, PECS-101 (1 mg/kg) administered along with PTX treatment caused a long-lasting relief of the mechanical and cold allodynia. These effects were blocked by a PPARγ, but not CB1 and CB2 receptor antagonists. Notably, the effects of PECS-101 on the relief of PTX-induced mechanical and cold allodynia were not found in macrophage-specific PPARγ-deficient mice. PECS-101 also decreased PTX-induced increase in Tnf, Il6, and Aif1 (Iba-1) gene expression in the DRGs and the loss of intra-epidermal nerve fibers. PECS-101 did not alter motor coordination, produce tolerance, or show abuse potential. In addition, PECS-101 did not interfere with the chemotherapeutic effects of PTX. Thus, PECS-101, a new fluorinated CBD analog, could represent a novel therapeutic alternative to prevent mechanical and cold allodynia induced by PTX potentially through the activation of PPARγ in macrophages., (© 2021. The American Society for Experimental NeuroTherapeutics, Inc.)

The peripheral nervous system comprises an infinity of neural networks that act in the communication between the central nervous system and the most diverse tissues of the body. Along with the extension of the primary sensory neurons (axons and cell bodies), a population of resident macrophages has been described. These newly called sensory neuron-associated macrophages (sNAMs) seem to play an essential role in physiological and pathophysiological processes, including infection, autoimmunity, nerve degeneration/regeneration, and chronic neuropathic pain. After different types of peripheral nerve injury, there is an increase in the number and activation of sNAMs in the sciatic nerve and sensory ganglia. The activation of sNAMs and their participation in neuropathic pain development depends on the stimulation of pattern recognition receptors such as Toll-like receptors and Nod-like receptors, chemokines/cytokines, and microRNAs. On activation, sNAMs trigger the production of critical inflammatory mediators such as proinflammatory cytokines (eg, TNF and IL-1β) and reactive oxygen species that can act in the amplification of primary sensory neurons sensitization. On the other hand, there is evidence that sNAMs can produce antinociceptive mediators (eg, IL-10) that counteract neuropathic pain development. This review will present the cellular and molecular mechanisms behind the participation of sNAMs in peripheral nerve injury-induced neuropathic pain development. Understanding how sNAMs are activated and responding to nerve injury can help set novel targets for the control of neuropathic pain., Competing Interests: The authors have no conflicts of interest to declare. T.M. Cunha receives funding from the São Paulo Research Foundation (FAPESP) under grant agreements 2013/08216-2 (Center for Research in Inflammatory Disease) and 2017/50419-9. C.E.A. Silva and R.M. Guimarães have a PhD fellowship from FAPESP (2020/05446-0 and 2019/13829-0).Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)