Previous studies have shown that the effects of manual acupuncture (MA) are contributed by collagen fibers and mast cells in local acupoints, at which acupuncture stimulation causes various afferent fiber groups to be excited. However what happens in local nerve fibers and mast cells after MA remains unclear. The aim of this study was to examine the response of cutaneous nerve fibers and mast cells to MA stimulation in acupoint Hegu (LI4). The contralateral LI4 of the same rat was used as a non-stimulated control. Immnohistochemistry analysis were carried out to observe the expression of histamine (HA), serotonin (5-HT) and nociceptive neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), in the LI4 area. Mast cells were labeled with anti-mast cell tryptase antibody and simultaneously with HA or 5-HT primary antibodies to observe their co-expression. Our results showed that SP and CGRP were expressed more highly on the cutaneous nerve fibers of LI4 after MA stimulation than that of the control. Mast cells aggregated in close proximity to the blood vessels in intra-epidermis and dermis and some of them with degranulation in the lower dermis and subcutaneous tissue of LI4. Both mast cells and their granules appeared with HA (+) and 5-HT (+) expression at stimulated L14 sites, while a few intact mast cells with a little expression of 5-HT and HA were distributed in areas of non-stimulated L14. The results indicated that local cutaneous nerve terminals and mast cells responded to MA with higher expression of SP and CGRP in nerve fibers, as well as with aggregation and degranulation of mast cells with HA and 5-HT granules at acupoint LI4. These neuroactive substances may convey signals to certain pathways that contribute to the effects of acupuncture.

Charcot–Marie–Tooth (CMT) disease is a hereditary neuropathy mainly caused by gene mutation of peripheral myelin proteins including myelin protein zero (P0, MPZ). Large myelin protein zero (L-MPZ) is an isoform of P0 that contains an extended polypeptide synthesized by translational readthrough at the C-terminus in tetrapods, including humans. The physiological role of L-MPZ and consequences of an altered L-MPZ/P0 ratio in peripheral myelin are not known. To clarify this, we used genome editing to generate a mouse line (L-MPZ mice) that produced L-MPZ instead of P0. Motor tests and electrophysiological, immunohistological, and electron microscopy analyses show that homozygous L-MPZ mice exhibit CMT-like phenotypes including thin and/or loose myelin, increased small-caliber axons, and disorganized axo–glial interactions. Heterozygous mice show a milder phenotype. These results highlight the importance of an appropriate L-MPZ/P0 ratio and show that aberrant readthrough of a myelin protein causes neuropathy.

The previous study showed that the cardiac arrhythmias induced by myocardial ischemia and reperfusion were attenuated by the pretreatment of acupuncture; however, the related mechanism is not understood. The present study was therefore designed to determine whether intracellular Ca2+ ([Ca2+]i) and connexin 43 (Cx43) are involved in the mediation of the anti-arrhythmic effect of electro-acupuncture (EA) pretreatment in the rats subjected to simulative global ischemia and reperfusion (SGIR). SGIR was made in the isolated heart by a low flow perfusion followed by a flow restoration. Four groups of animals are involved in the present study, including normal control group, SGIR group, EA group and EA plus 18 beta-glycyrrhetinic acid (EAG) group. For EA pretreatment, bilateral Neiguan acupoints (PC6) of the rats were stimulated for 30 min once a day in 3 consecutive days. Cx43 antagonist was given to the rats in EAG group 30 minutes before the EA pretreatment. The resting [Ca2+]i concentration, calcium oscillation, the contents of total Cx43 and non-phosphrylated Cx43 and arrhythmia score were compared among different groups. In EA group, the arrhythmic score, the resting [Ca2+]i concentration and the number of [Ca2+]i oscillations were all significantly less than those in SGIR group (all P < 0.05), and interestingly, after EA pretreatment, the contents of nonphosphated Cx43 in the EA group were significantly lower than that in SGIR group respectively (P < 0.05). However, when the rats were treated with Cx43 antagonist prior to the EA pretreatment, the protection effects induced by EA pretreatment were reversed. The results showed that EA pretreatment could produce anti-arrhythmic effect in the rats subjected to SGIR. The anti-arrhythmic effect of EA pretreatment may be due at least partially to the inhibition of SGIR-induced calcium overload and [Ca2+]i oscillations, reduction of non-phosphorylated Cx43 and the enhancement of the corresponding phosphorylated Cx43 in the cardiac cells.

Pregabalin is a medication primarily used in the treatment of neuropathic pain and anxiety disorders, owing to its gabapentinoid properties. Pregabalin monotherapy faces limitations due to its variable efficacy and dose-dependent adverse reactions. In this study, we conducted a comprehensive investigation into the potentiation of pregabalin’s analgesic effects by dexborneol, a neuroprotective bicyclic monoterpenoid compound. We performed animal experiments where pain models were induced using two methods: peripheral nerve injury, involving axotomy and ligation of the tibial and common peroneal nerves, and incisional pain through a longitudinal incision in the hind paw, while employing a multifaceted methodology that integrates behavioral pharmacology, molecular biology, neuromorphology, and lipidomics to delve into the mechanisms behind this potentiation. Dexborneol was found to enhance pregabalin’s efficacy by promoting its transportation to the central nervous system, disrupting self-amplifying vicious cycles via the reduction of HMGB1 and ATP release, and exerting significant anti-oxidative effects through modulation of central lipid metabolism. This combination therapy not only boosted pregabalin’s analgesic property but also notably decreased its side effects. Moreover, this therapeutic cocktail exceeded basic pain relief, effectively reducing neuroinflammation and glial cell activation—key factors contributing to persistent and chronic pain. This study paves the way for more tolerable and effective analgesic options, highlighting the potential of dexborneol as an adjuvant to pregabalin therapy.

Objective. To collect and summarize relevant literatures on the experimental researches of sciatic nerve injury (SNI) with acupuncture during the last decade providing a guideline for effectively treating SNI with acupuncture in the future. Methods. The Chinese and English databases including China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (WanFang Data), VIP Information Chinese Journal Service Platform (VIP Date), and PubMed were searched from 2009 to 2020 with keywords of acupuncture and moxibustion OR acupuncture OR electroacupuncture OR scalp acupuncture OR wrist-ankle acupuncture OR acupoint injection OR ear acupuncture AND sciatic nerve OR sciatic nerve injury OR sciatic injury OR SNI. The collected data were mainly evaluated in the items of animal model of SNI, type of interventions, selection of acupuncture points (acupoints), course of treatment and its frequency, and approaches of assessment. Results. A total of 89 studies were included in this analysis. Among them, the most commonly used animal models of SNI were produced by the clamp or transverse injury in the rats; the most frequently used intervention was electroacupuncture with dilatational wave of 2/100Hz; the frequency of acupuncture was mainly performed once per day lasting for more than 2 weeks; the mainly selected acupoints were Huantiao (GB30), Zusanli (ST36), and Yanglingquan (GB34); and the approaches of assessment were contained with behavioral, functional, morphological, histological, cellular, and molecular measurements. Conclusion. The results indicated that the experimental researches of SNI with acupuncture has made marked progress in recent years, which may provide important clues for further investigating the underlying mechanisms of acupuncture for the treatment of SNI in the future.

Objective: To compare the effects of carbamyl-β -methylcholine chloride (CMCC) administered by intra-acupuncture point injection (IAI), intramuscular injection (IMI), and intravenous injection (IVI), and to analyze the mechanisms. Methods: In the IAI group, CMCC was injected into the Zusanli acupoint (ST 36) immediately after 30-min stimulation by electro-acupuncture (EA) at the acupoints, and into the femoral vein and skeletal muscle in IVI and IMI groups, respectively. Intragastric pressure was detected. The plasma concentration of CMCC was measured at various times. Results: The gastric effect of CMCC in the IVI group was enhanced and attenuated more rapidly than in the other groups. In the IAI group, this effect was significantly stronger than that in the IMI group at 2 min and 15 min, but not significantly different between the two groups at 5 min and 30 min. Plasma concentration of CMCC in the IAI group was similar to that in the IVI group at 2 min, but higher than that in the IMI group. The concentration in the IAI group was higher than that in the IV group and similar to that in the IMI group at 5, 15 and 30 min, indicating rapid increase and slower reduction of the plasma concentration of the drug in the IAI group. There was a positive correlation between the plasma concentration of CMCC and intragastric pressure in all groups. Conclusion: The effect of IAI with CMCC was stronger than that of IMI and longer-lasting than that of IVI, which correlated with the blood concentration of CMCC.