电针和经皮穴位电刺激技术在生殖医学中的应用:专家共识（英文）

本文从传统针刺治疗不孕症的选穴依据与现代电针/经皮穴位电刺激技术的相关原理着手,从最优刺激参数选择、穴位辨证、疗程与治疗次数的确定及基本原理等方面阐述了电针/经皮穴位电刺激技术在多囊卵巢综合症、取卵镇痛、卵巢储备功能降低、胚胎移植以及男性少/弱精症等生殖领域中的具体应用。首次对电针/经皮穴位电刺激技术在生殖领域优势病种中的应用进行了系统的分析和总结,在最优刺激参数选择、穴位辨证、疗程与治疗次数的确定等方面提出了一系列专家共识,并为临床实践提供了指导意见和理论依据。

Formaldehyde up-regulates TRPV1 through MAPK and PI3K signaling pathways in a rat model of bone cancer pain

Objective Our previous study showed that tumor tissue-derived formaldehyde at low concentrations plays an important role in bone cancer pain through activating transient receptor potential vanilloid subfamily member 1 （TRPV 1）. The present study further explored whether this tumor tissue-derived endogenous formaldehyde regulates TRPV1 expres- sion in a rat model of bone cancer pain, and if so, what the possible signal pathways are during the development of this type of pain. Methods A rat model of bone cancer pain was established by injecting living MRMT-1 tumor cells into the tibia. The formaldehyde levels were determined by high performance liquid chromatography, and the expression of TRPV1 was examined with Western blot and RT-PCR. In primary cultured dorsal root ganglion （DRG） neurons, the ex- pression of TRPV1 was assessed after treatment with 100 ~tmol/L formaldehyde with or without pre-addition of PD98059 [an inhibitor for extracellular signal-regulated kinase], SB203580 （a p38 inhibitor）, SP600125 [an inhibitor for c-Jun N- terminal kinase], BIM [a protein kinase C （PKC） inhibitor] or LY294002 [a phosphatidylinositol 3-kinase （PI3K） inhibi- tor]. Results In the rat model of bone cancer pain, formaldehyde concentration increased in blood plasma, bone marrow and the spinal cord. TRPV1 protein expression was also increased in the DRG. In primary cultured DRG neurons, 100 p^mol/L formaldehyde significantly increased the TRPV1 expression level. Pre-incubation with PD98059, SB203580, SP600125 or LY294002, but not BIM, inhibited the formaldehyde-induced increase of TRPV1 expression. Conclusion Formaldehyde at a very low concentration up-regulates TRPV1 expression through mitogen-activated protein kinase and PI3K, but not PKC, signaling pathways. These results further support our previous finding that TRPV1 in peripheral after- ents plays a role in bone cancer pain.

Responses of Primary Afferent Fibers to Acupuncture-Like Peripheral Stimulation at Different Frequencies:Characterization by Single-Unit Recording in Rats

The pain-relieving effect of acupuncture is known to involve primary afferent nerves(PANs) via their roles in signal transmission to the CNS.Using single-unit recording in rats,we characterized the generation and transmission of electrical signals in Aβ and Aδ fibers induced by acupuncture-like stimuli.Acupuncture-like signals were elicited in PANs using three techniques:manual acupuncture(MAc),emulated acupuncture(EAc),and electro-acupuncture(EA)-like peripheral electrical stimulation(PES).The discharges evoked by MAc and EAc were mostly in a burst pattern with average intra-burst and inter-burst firing rates of 90 Hz and 2 Hz,respectively.The frequency of discharges in PANs was correlated with the frequency of PES.The highest discharge frequency was 246 Hz in Aβ fibers and 180 Hz in Aδ fibers.Therefore,EA in a dense-disperse mode(at alternating frequency between 2 Hz and 15 Hz or between 2 Hz and 100 Hz) best mimics MAc.Frequencies of EA output>250 Hz appear to be obsolete for pain relief.

Formaldehyde increases intracellular calcium concentration in primary cultured hippocampal neurons partly through NMDA receptors and T-type calcium channels

Objective Formaldehyde at high concentrations is a contributor to air pollution. It is also an endogenous metabolic product in cells, and when beyond physiological concentrations, has pathological effects on neurons. Formaldehyde induces mis-folding and aggregation of neuronal tau protein, hippocampal neuronal apoptosis, cognitive impairment and loss of memory functions, as well as excitation of peripheral nociceptive neurons in cancer pain models. Intracellular calcium （[Ca2＋]i） is an important intracellular messenger, and plays a key role in many pathological processes. The present study aimed to investigate the effect of formaldehyde on [Ca2＋]i and the possible involvement of N-methyl-D-aspartate receptors （NMDARs） and T-type Ca2＋ channels on the cell membrane. Methods Using primary cultured hippocampal neurons as a model, changes of [Ca2＋]i in the presence of formaldehyde at a low concentration were detected by confocal laser scanning microscopy. Results Formaldehyde at 1 mmol/L approximately doubled [Ca2＋]i. （2R）-amino-5-phosphonopentanoate （AP5, 25 μmol/L, an NMDAR antagonist） and mibefradil （MIB, 1 μmol/L, a T-type Ca2＋ channel blocker）, given 5 min after formaldehyde perfusion, each partly inhibited the formaldehyde-induced increase of [Ca：＋]i, and this inhibitory effect was reinforced by combined application of AP5 and MIB. When applied 3 min before formaldehyde perfusion, AP5 （even at 50μmol/L） did not inhibit the formaldehyde-induced increase of [Ca2＋]i, but MIB （1 μmol/L） significantly inhibited this increase by 70%. Conclusion These results suggest that formaldehyde at a low concentration increases [Ca2＋]i in cultured hippocampal neurons; NMDARs and T-type Ca2＋ channels may be involved in this process.