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Background: Paclitaxel-induced peripheral neuropathy (PIPN) is prevalent among patients receiving paclitaxel chemotherapy, which results in sensory abnormality as well as neuropathic pain. Conventional medications lack effectiveness on PIPN. Clinical trials identified beneficial effects of acupuncture on PIPN among patients receiving chemotherapy. Here we explored the mechanisms underlying how acupuncture might alleviate PIPN. Methods: A mouse model of PIPN was established by repeated paclitaxel application. Electroacupuncture (EA) was applied at ST36 and BL60 acupoints of model mice. Immunostaining, flow cytometry, behavioral assay, in vivo imaging were utilized for effects determination and mechanism exploration. Results: EA ameliorated mechanical and cold pain hypersensitivities, reduced sensory neuron damage and improved loss in intra-epidermal nerve fibers (IENFs) in model mice. Macrophages infiltration were detected in DRG and sciatic nerve of model mice, which was reduced by EA. EA affected M1-like pro-inflammatory macrophage infiltration in DRG, whereas it did not affect M2-like macrophages. DRG neurons released chemoattractant CCL2 that recruited macrophages via CCR2 to DRG. EA reduced CCL2 overproduction by DRG neurons and reduced macrophage infiltration. Blocking CCR2 mimicked EA's anti-allodynic effect, whereas exogenously applying recombinant CCL2 reversed the ameliorative effect of EA on macrophage infiltration and abolished EA's anti-allodynia on model mice. EA ameliorated other signs of PIPN, including sensory neuron damage, sciatic nerve morphology impairment and IENFs loss. In mice inoculated with breast cancer cells, EA didn't affect paclitaxel-induced antitumor effect. Conclusions: These findings suggest EA alleviates PIPN by reducing CCL2/CCR2 mediated-pro-inflammatory macrophage infiltration into sensory ganglia as well as the sciatic nerve. Our study supports EA could be used as a potential non-pharmacological therapy for PIPN. [ABSTRACT FROM AUTHOR]

Simple Summary: Various physiological activities of organisms, including movement, feeding, reproduction, breathing, excretion, etc., all require the participation of their neuromuscular systems. Echinoderms, a phylum closely related to chordates, possess a well-differentiated but simpler muscular system, which provides a great opportunity to trace the evolutionary origins of the vertebrate muscular system. Here, we review the morphology of different musculatures and the effects of different neurotransmitters and neuropeptides involved in muscle regulation in echinoderms. In addition, we highlight the potential molecular mechanisms underpinning the action of these chemical messengers on echinoderm muscles. The muscular systems of echinoderms play important roles in various physiological and behavioral processes, including feeding, reproduction, movement, respiration, and excretion. Like vertebrates, echinoderm muscle systems can be subdivided into two major divisions, somatic and visceral musculature. The former usually has a myoepithelial organization, while the latter contains muscle bundles formed by the aggregation of myocytes. Neurons and their processes are also detected between these myoepithelial cells and myocytes, which are capable of releasing a variety of neurotransmitters and neuropeptides to regulate muscle activity. Although many studies have reported the pharmacological effects of these chemical messengers on various muscles of echinoderms, there has been limited research on their receptors and their signaling pathways. The muscle physiology of echinoderms is similar to that of chordates, both of which have the deuterostome mode of development. Studies of muscle regulation in echinoderms can provide new insights into the evolution of myoregulatory systems in deuterostomes. [ABSTRACT FROM AUTHOR]

Vasopressin/oxytocin (VP/OT)-type neuropeptide is an ancient neurophysin-associated neuropeptide and has been intensively studied to be involved in multiple physiological processes in protostomian and deuterostome vertebrates. However, little is known about the functions of VP/OT-type neuropeptide in deuterostome invertebrates especially in echinoderms. Here, we firstly report VP/OT-type neuropeptide signaling in an important economic species, Apostichopus japonicus, which is widely cultured in Asia, with high nutritional and medicinal values. Molecular characterization analysis of holotocin and its precursor revealed the highly conserved features of VP/OT family. The candidate receptor for holotocin (AjHOR) was confirmed to be able to activate the signaling via cAMP-PKA and possible Ca2+-PKC pathway, and further activated the downstream ERK1/2 cascade. Holotocin precursor expression profile showed that they were mainly concentrated in circumoral nerve ring. Furthermore, in vitro pharmacological experiments demonstrated that holotocin caused contractile responses in preparations from A. japonicus. And in vivo functional studies indicated that short-term injection of holotocin resulted in body bloat and long-term injection resulted in reduced body mass, suggesting potential roles of holotocin in osmoregulation and feeding co-inhibition with holotocin–CCK. Our findings provided a comprehensive description of AjHOR–holotocin signaling, revealed ancient roles of holotocin in osmoregulation and feeding inhibition by controlling muscle contractions. [ABSTRACT FROM AUTHOR]