A C-fiber reflex inhibition induced by electroacupuncture with different intensities applied at homotopic and heterotopic acupoints in rats selectively destructive effects on myelinated and unmyelinated afferent fibers

doi:10.1016/j.brainres.2004.03.034

Brain Research

Volume 1011, Issue 2, 18 June 2004, Pages 228-237

https://doi.org/10.1016/j.brainres.2004.03.034 Get rights and content

Abstract

The aims of this study were to explore the C-fiber reflex inhibition induced by electroacupuncture with different intensities applied at homotopic or heterotopic acupoints, and to determine the influence selectively destroyed myelinated and unmyelinated afferent fibers on the C-fiber reflex inhibition. In the ipsilateral local acupoint, the general behavior of the C-fiber reflex can be depressed by electroacupuncture below the threshold of Aδ-fiber activation. Electroacupuncture stimulation within the intensity of Aδ-fiber activation applied to the ipsilateral limb pretreated with cobra venom did not elicit inhibition of C-fiber reflex in rats with demyelinated sciatic nerve. However, heterotopic electroacupuncture below the threshold of Aδ-fiber activation was totally ineffective. In contralateral heterotopic acupoints, the C-fiber reflex can be depressed only by electroacupuncture with stimulating intensities exceeding thresholds of Aδ and C-fiber activation. Electroacupuncture stimuli applied to capsaicin-pretreated limb in the intensities of threshold of Aδ-fiber and treble thresholds of C-fiber activation produced only a little inhibition of C-fiber reflex. Inhibitory intensity was roughly similar to that induced by the stimulation with intensity for the activation of Aδ-fiber in normal animal. In the spinalized animals transections at T₆–T₇ segments, regardless of intensities, the homotopic electroacupuncture stimulation only induced moderate depression of C-fiber reflex similar to that of Aδ-fiber activation; whereas, no matter what intensities of application, the inhibitory effects of C-fiber reflex disappeared totally by using heterotopic noxious electroacupuncture in these animals.

Introduction

Acupuncture-induced analgesia is widely accepted [2], [5], [7]. However, the functional specificity of acupoints has rarely been investigated and the regional range of analgesia induced by the stimulation at the acupoints in the different parts of the body is still unclear [16], [36].

The transmission of nociceptive signals can be modulated by powerful controls at the first spinal relays including both the segmental mechanism and systemic mechanism that involves supra-spinal structures, and some of them can be triggered by somesthetic stimuli [4], [17], [21], [33]. This is true not only for non-noxious stimulation of large diameter cutaneous fibers that triggers segmental mechanisms in the corresponding dermatome, but also for nociceptive stimuli that elicit heterotopic, i.e., non-segmental inhibition.

In order to explore the functional specificity of acupoints in different parts of the body and in peri-segmental fields, the C-fiber activation-induced nociceptive reflex was investigated in rats treated with electroacupuncture stimulation at homotopic and heterotopic acupoints in the present study. A preliminary report of this work has previously appeared [37].

Section snippets

Animal preparation

All the animal experiments in the present study were approved authoritatively in accordance with the “Guide for Care and Use of Laboratory Animals” issued by NIH. The experiments were performed on 76 male Sprague–Dawley rats weighing 200–300 g. The animals were housed with ad libitum access to food and water in a room illuminated from 0700 to 1800 h. The animals were anesthetized with 10% urethane (1 g/kg, ip) and artificially ventilated through a tracheal cannula; the rate (60 strokes/min) and

General characteristics of Aδ- and C-fiber-mediated reflex responses of EMG

Electrical stimulation with a duration of 1 ms, frequency of 0.2 Hz, and intensity of 1.2 times of the threshold for the activation of Aδ- and C-fiber-mediated reflex on the sural nerve territory elicited a reflex response of EMG with two components in the ipsilateral biceps femoris muscle. The first component was a single di- or triphasic response with a short latency (12.9±1.5 ms), a short duration (22.3±1.8 ms) and a low threshold (1.63±0.52 mA). The second component was generally

Aδ- and C-fiber-mediated reflex response

In the present study, the reflex EMG signals of the biceps femoris muscle in the intact anesthetized and spinalized rats, elicited by electrical stimulation of the sural nerve receptive field, seems to be related to the activation of peripheral Aδ- and C-fiber afferents and were thus termed as the Aδ- and C-fiber-mediated reflexes that mainly consists of two-components separated by periods of an EMG absence [11]. Our results are very similar to those described by Falinower et al. [12] that

Acknowledgements

The authors thank Prof. Y.K. Xie for the technical assistance that selectively demyelinated fibers by cobra venom. We thank Dr. X.C. Yu for the advice in the preparation of this manuscript. This work was supported by the Research Program (1997–2001) of Ministry of Science–Technology of China and State Administration of TCM.

References (38)

S.A Andersson et al.
Acupuncture—from empiricism to science: functional background to acupuncture effects in pain and disease
Med. Hypotheses
(1995)
D Bouhassira et al.
The spinal transmission of nociceptive information: modulation by the caudal medulla
Neuroscience
(1995)
S.W Cadden
The digastric reflex evoked by tooth-pulp stimulation in the cat and its modulation by stimuli applied to the limbs
Brain Res.
(1985)
S.W Cadden et al.
Depression of activities of dorsal horn convergent neurones by propriospinal mechanisms triggered by noxious inputs; comparison with diffuse noxious inhibitory controls (DNIC)
Brain Res.
(1983)
D Le Bars
The whole body receptive field of dorsal horn multireceptive neurons
Brain Res. Rev.
(2002)
D Le Bars et al.
Diffuse noxious inhibitory controls (DNIC): I. Effects on dorsal horn convergent neurones in the rat
Pain
(1979)
C.R Morton et al.
Diffuse noxious inhibitory controls of lumbar spinal neurons involve a supraspinal loop in the cat
Brain Res.
(1987)
J Schouenborg et al.
Effects of a distant noxious stimulation on A and C fibre-evoked flexion reflexes and neuronal activity in the dorsal horn of the rat
Brain Res.
(1985)
J.C Willer et al.
Diffuse noxious inhibitory controls (DNIC) in man: involvement of an opioidergic link
Eur. J. Pharmacol.
(1990)
J.C Willer et al.
Neurophysiological bases of the counterirritation phenomenon: diffuse control inhibitors induced by nociceptive stimulation
Neurophysiol. Clin.
(1999)

S.A Andersson et al.

On acupuncture analgesia and the mechanism of pain

Am. J. Chin. Med.

(1975)

H Bao et al.

C fiber is not necessary in electroacupuncture analgesia, but necessary in diffuse noxious inhibitory controls (DNIC)

Acup. Res.

(1991)

J.M Besson et al.

Peripheral and spinal mechanisms of nociception

Physiol. Rev.

(1987)

S Birch et al.

Acupuncture Efficacy: A Summary of Controlled Clinical Trials

(1996)

D Bowsher

Physiology and pathophysiology of pain

J. British. Med. Acup. Soc.

(1990)

A.H Dickenson et al.

Diffuse noxious inhibitory controls (DNIC) involve trigeminothalamic and spinothalamic neurones in the rat

Exp. Brain Res.

(1983)

M.R Dimitrijevic et al.

Studies of spasticity in man. Changes in flexion reflex with repetitive cutaneous stimulation in spinal man

Brain

(1970)

S Falinower et al.

A C-fiber reflex modulated heterotopic noxious somatic stimuli in the rat

J. Neurophysiol.

(1994)

H.S Gasser et al.

The role played by the sizes of the constituent fibers of a nerve trunk in determining the form of its action potential wave

Am. J. Physiol.

(1927)

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Therefore, the phenomenon of acupoint sensitization in patients under pathological conditions is common. Acupoints have been determined to be surrounded by a high density of nerve endings, such as A- and C-type neurons, which can perceive nociception (Li et al., 2004; Zhu et al., 2004; Wick et al., 2007). Nociceptive neuropeptides including SP, CGRP and 5-HT are highly expressed in acupoints (He et al., 2017).
Under pathological conditions, acupoint sensitization is the phenomenon of acupoints transforming from the stable state to the dynamic state. Evidences suggest that hyperpolarization-activated current (I_h), conducted by the hyperpolarization-activated/cyclic nucleotide-gated (HCN) channel, greatly contributes to the peripheral and central sensitization. However, the role of the I_h current in acupoint sensitization has not been explained. In the present study, changes in excitability, I_h density and the HCN channel of dorsal root ganglion (DRG) nociceptive neurons were examined in the later phase of knee osteoarthritis (KOA) rats. To investigate the neuronal specificity of acupoint sensitization, retrograde dyes were injected into the acupoints ST35 and GB37. The results showed that acupoint sensitization occurred in bilateral ST35 but not GB37 acupoints. The excitability and I_h density of C- but not A_δ-type neurons innervating ST35 acupoint increased in bilateral L5 DRG of acupoint sensitized rats than that of sham rats. No obvious changes were found in the excitability or I_h density of C- and A_δ-type neurons innervating the GB37 acupoint in the bilateral L5 DRG. HCN channel subtype 2 (HCN2) expression levels significantly increased after acupoint sensitization. Furthermore, ZD7288, an HCN current (I_h) blocker, attenuated the acupoint sensitization of the ST35 acupoint. Taken together, our findings suggest that the increased excitability of C- but not A_δ-type neurons and the upregulation of I_h/HCN2 channels contribute to the formation of acupoint sensitization.
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Research reportA C-fiber reflex inhibition induced by electroacupuncture with different intensities applied at homotopic and heterotopic acupoints in rats selectively destructive effects on myelinated and unmyelinated afferent fibers

Abstract

Introduction

Section snippets

Animal preparation

General characteristics of Aδ- and C-fiber-mediated reflex responses of EMG

Aδ- and C-fiber-mediated reflex response

Acknowledgements

Med. Hypotheses

Neuroscience

Brain Res.

Brain Res.

Brain Res. Rev.

Pain

Brain Res.

Brain Res.

Eur. J. Pharmacol.

Neurophysiol. Clin.

On acupuncture analgesia and the mechanism of pain

Am. J. Chin. Med.

C fiber is not necessary in electroacupuncture analgesia, but necessary in diffuse noxious inhibitory controls (DNIC)

Acup. Res.

Peripheral and spinal mechanisms of nociception

Physiol. Rev.

Acupuncture Efficacy: A Summary of Controlled Clinical Trials

Physiology and pathophysiology of pain

J. British. Med. Acup. Soc.

Diffuse noxious inhibitory controls (DNIC) involve trigeminothalamic and spinothalamic neurones in the rat

Exp. Brain Res.

Studies of spasticity in man. Changes in flexion reflex with repetitive cutaneous stimulation in spinal man

Brain

A C-fiber reflex modulated heterotopic noxious somatic stimuli in the rat

J. Neurophysiol.

The role played by the sizes of the constituent fibers of a nerve trunk in determining the form of its action potential wave

Am. J. Physiol.

Research report
A C-fiber reflex inhibition induced by electroacupuncture with different intensities applied at homotopic and heterotopic acupoints in rats selectively destructive effects on myelinated and unmyelinated afferent fibers