close

Вход

Забыли?

вход по аккаунту

?

Transcutaneous Electrical Nerve Stimulation on Yongquan Acupoint Reduces CFA-Induced Thermal Hyperalgesia of Rats via Down-Regulation of ERK2 Phosphorylation and c-Fos Expression.

код для вставкиСкачать
THE ANATOMICAL RECORD 293:1207–1213 (2010)
Transcutaneous Electrical Nerve
Stimulation on Yongquan Acupoint
Reduces CFA-Induced Thermal
Hyperalgesia of Rats via Down-Regulation
of ERK2 Phosphorylation and
c-Fos Expression
LIN YANG, LIANXUE YANG, AND XIULAI GAO*
Department of Anatomy, Histology and Embryology, Capital Medical University,
Beijing, People’s Republic of China
ABSTRACT
Activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and
its involvement in regulating gene expression in spinal dorsal horn, cortical and subcortical neurons by peripheral noxious stimulation contribute
to pain hypersensitivity. Transcutaneous electrical nerve stimulation
(TENS) is a treatment used in physiotherapy practice to promote analgesia in acute and chronic inflammatory conditions. In this study, a total
number of 114 rats were used for three experiments. Effects of complete
Freund’s adjuvant (CFA)-induced inflammatory pain hypersensitivity and
TENS analgesia on ERK1/2 phosphorylation and c-Fos protein expression
were examined by using behavioral test, Western blot, and immunostaining methods. We found that CFA injection caused an area of localized
swelling, erythema, hypersensitivity to thermal stimuli, the decreased
response time of hind paw licking (HPL), as well as upregulation of c-Fos
protein expression and ERK2 phosphorylation in the ipsilateral spinal
dorsal horn and the contralateral primary somatosensory area of cortex
and the amygdala of rats. TENS on Yongquan acupoint for 20 min produced obvious analgesic effects as demonstrated with increased HPL to
thermal stimuli of CFA-treated rats. In addition, TENS application suppressed the CFA-induced ERK2 activation and c-Fos protein expression.
These results suggest that down-regulation of ERK2 phosphorylation and
c-Fos expression were involved in TENS inhibition on CFA-induced therC 2010 Wileymal hyperalgesia of rats. Anat Rec, 293:1207–1213, 2010. V
Liss, Inc.
Key words: CFA-induced inflammatory pain; TENS application;
ERK1/2; c-Fos
Grant sponsor: National Natural Science Foundation of China;
Grant number: 90209008; Grant sponsor: Beijing Natural
Science Foundation; Grant number: 5072008.
*Correspondence to: Xiulai Gao, MD, Department of Anatomy,
Histology and Embryology, Capital Medical University, Beijing
100069, China E-mail: yanglin@ccmu.edu.cn
C 2010 WILEY-LISS, INC.
V
Received 10 October 2009; Accepted 31 January 2010
DOI 10.1002/ar.21157
Published online 13 April 2010 in Wiley InterScience (www.
interscience.wiley.com).
1208
YANG ET AL.
Inflammatory and neuropathic pains are initiated by
tissue damage/inflammation and nervous system lesions,
and both are characterized by hypersensitivity at the
site of damage and in adjacent normal tissue (Woolf and
Salter, 2000). Up to now, intraplantar or joint injection
of the complete Freund’s adjuvant (CFA) as an inflammatory pain model has been widely used (Kim et al.,
2006). The nociceptive system in the central nervous system (CNS) includes the spinal dorsal horn, the primary
somatosensory cortex (SI), and the amygdala (Woolf,
2007). It has been reported that both inflammation and
nerve injury induce transcriptional changes in dorsal
horn neurons, which are mediated by activation of the
mitogen-activated protein kinases (MAPK)-cAMP response
element binding protein cascade (McCarson and Krause,
1994; Hay et al., 1997). SI cortical neurons encode the
intensity of tactile and nociceptive stimuli. Neurons in
the medial temporal lobe areas, including the amygdala,
are involved in learning the association between aversive and neutral stimuli in normal conditions (Buchel
and Dolan, 2000; Petrovic et al., 2000; Petrovic et al.,
2002). The amygdala may contribute to pain processing
both directly by regulating nociceptive modulating systems in the brainstem and indirectly by controlling behavioral and autonomic output during pain (Petrovic
et al., 2000; Petrovic et al., 2004).
c-Fos is the most extensively investigated member of
the immediate early gene family (IEGs). It has been considered a transcription factor and a cellular marker of
neural activity to identify activated neurons response to
peripheral noxious stimulation in the CNS. Numerous
studies have demonstrated that noxious stimuli induce
the expression of c-Fos in the SI area, the amygdala,
and the spinal dorsal horn (Kwon et al., 2004; Roh
et al., 2006). The activation of ERK1/2, a well known
member of MAPK family, is mediated via the conserved
Ras/Raf/MAPK pathway (Ji et al., 1999). Phosphorylated ERK1/2 (p-ERK1/2) has been also used as a
marker of neural activation (Ji et al., 2002; Kawasaki
et al., 2004). However, few studies have been carried
out to investigate ERK1/2 activation and expression in
the SI area and the amygdala after inflammatory pain
stimulation.
Transcutaneous electrical nerve stimulation (TENS) is
a treatment that has been shown to be effective for pain
relief in a variety of conditions (Bjordal et al., 2003;
Chao et al., 2007). Acupuncture is also an important
therapeutic strategy in traditional Chinese medicine
(Zhang et al., 2003; Kim et al., 2005). However, acupuncture typically involves penetration of the skin on the
specific points (named as acupoints) by a needle, and
the analgesic effect varies in the different conditions.
TENS on acupoints may serve as a relatively safe and
noninvasive method to obtain the analgesic effect. In
this study, we observed the TENS effects on phosphorylation and protein expression levels of ERK1/2 and c-Fos
expression in the spinal dorsal horn, the SI area, and
the amygdala of rats following CFA injection using
TENS on Yongquan acupoint (KI 1). KI 1 is located on
the sole of the foot, at the indentation near the front
part, between the second and third metatarsal bones,
one-third of the distance from the webs of the toes to
the heel. KI 1 is usually applied to reduce pain on top of
the head, blurry vision, throat numbness, and so forth
(Lu and Liu, 1991).
TABLE 1. Experimental groups
1
2
3
4
5
6
Saline only
Saline þ Sham TENS
Saline þ TENS
CFA only
CFA þ Sham TENS
CFA þ TENS
HPL test
IHC test
WB test
6
6
6
6
6
6
6
0
6
6
0
6
6
0
6
30a
0
12b
Rats in different groups were sacrificed at 1 hr after saline
or CFA injection.
a
Rats were sacrificed at five different time points (0.5, 1, 2,
24, and 48 hr after CFA injection).
b
Rats were sacrificed at two different time points (1 and 24
hr after CFA injection). TENS was applied for 20 min 0.5
and 23.5 hr after CFA injection.
MATERIALS AND METHODS
Animals and Drugs
All experiments were carried out on specific pathogenfree adult (range, 12–16 weeks of age) male Wistar rats
(weighing range, 180–230 g). The animal protocols were
approved by University Institutional Animal Care and
Use Committee of Capital Medical University, and were
consistent with the NIH policy on the use of experimental animal (NIH Publications No. 80-23). A total of 114
rats were used in six different groups (see Table 1).
Group 1 (Saline only): Eighteen rats were injected with
0.1 mL saline solution into the right ankle joint and
tested or sacrificed 1 hr after injection. Out of 18 rats in
Group 1, six rats were used for hind paw licking (HPL)
test, six for immunohistochemistry (IHC), and six for
western blot (WB), respectively; Group 2 (Saline þ sham
TENS): Six rats were injected with 0.1 mL saline solution, treated with sham TENS for 20 min 0.5 hr after
injection and used for HPL test at 1 hr after injection;
Group 3 (Saline þ TENS): 18 rats were injected with 0.1
mL saline solution, applied TENS for 20 min 0.5 hr after
injection and tested or sacrificed at 1 hr after injection.
Out of 18 rats in Group 3, six rats were used for HPL
test, six for IHC, and six for WB, respectively; Group 4
(CFA only): 12 rats were used for HPL test and IHC
respectively, which were injected with 0.1 mL CFA and
tested or sacrificed 1 hr after injection. Another 30 rats
were used for WB, which were sacrificed at five different
time points (0.5, 1, 2, 24, and 48 hr after CFA injection);
Group 5 (CFA þ sham TENS): Six rats were injected
with 0.1 mL CFA, treated with sham TENS and used for
HPL test at 1 hr after injection; Group 6 (CFA þ TENS):
18 rats were injected with 0.1 mL CFA, applied TENS
for 20 min 0.5 hr after injection and tested or sacrificed
at 1 hr after injection. Another six rats were treated
with TENS 23.5 hr after CFA injection and sacrificed
24 hr after CFA injection.
CFA (0.1mL per animal, Gibco, USA) was injected into
the right ankle joint to produce a pathological pain
model as previously reported (Abbadie et al., 1994).
TENS Application
A TENS device (HANS LH202H, Beijing Huawei Company, Beijing, China) was used to induce antihyperalgesia. The following parameters were used: low (LF, 2 Hz)
and high (HF, 100 Hz) frequency alternately, with
1209
TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION
TABLE 2. Changes in response time of hind paw licking of rats after CFA
injection and TENS application (N 5 6 per group)
Control
CFA injection
Number (N)
Before TENS
stimulation (S)
After sham TENS
stimulation (S)
After TENS
stimulation (S)
18
18
8.65 1.68
5.12 1.29*
9.04 2.25
6.26 2.17*
14.72 3.84#
9.86 1.58*,#
Versus control group, *P < 0.05; versus sham TENS stimulation, #P < 0.05; S, seconds.
current intensity at range, 1–3 mA, and pulse duration
at range, 0.2–0.6 ms. TENS was applied on KI 1 acupoint in the right hind limbs of rats at 0.5 hr or 23.5 hr
after the injection of CFA or physiological saline solution
and maintained for 20 min. Then the rats were tested
for the response time of HPL or were sacrificed at the
time point of 1 hr or 24 hr after CFA-injection. The parameters of TENS regarding frequency, pulse duration,
application time, and intensity were in accordance to
those used in routine physiotherapy practice (Han,
2003). Rats with sham TENS treatment were placed in a
TENS device without electric current.
Hyperalgesia was examined with measuring the
response time of HPL to thermal stimuli using a hot
plate analgesia meter (Hargreaves et al., 1988). The hot
plate meter (YLS-6B, Huaibei Zhenghua Instruments &
Equipments Company, China) was maintained at 52 0.2 C. Because of individual variations, the animals
used in this study were chosen with the HPL response
time shorter than 20 sec but longer than 6 sec under the
normal condition.
Immunostaining Study
Rats were deeply anesthetized with chloral hydrate
(300 mg/kg, ip), transcardially perfused with 0.1 M phosphate-buffered saline (PBS) followed by cold 4% paraformaldehyde in PBS. The lumbar-sacral enlargement of
the spinal cord and the brain were postfixed in 4% paraformaldehyde and dehydrated in 20% sucrose solution
overnight. Sections at 30 lm thickness were prepared
for c-Fos IHC staining. Sections were incubated with
0.3% H2O2 in PBS (0.5 hr), blocked in 5% normal goat
serum (60 min), and incubated overnight with primary
antibody c-Fos (1:100, Santa Cruz), then with biotinylated goat anti-rabbit IgG. Finally, sections were developed with DAB (Sigma, USA) staining. c-Fos positive
neurons in the spinal dorsal horn, the S1 area of the cortex, and the amygdala were counted in five representative sections. Five areas (126.50 lm2 per area) were
chosen for cell counts from each section.
Western Blotting
Rats were anesthetized with chloral hydrate (250 mg/
kg, ip) and decapitated at each time point. The tissues
from the bilateral spinal cord, the SI area of the cortex,
and the amygdala were immediately removed. The sectioned tissues were homogenized at 4 C in homogenizing
buffer and sonicated to dissolve the tissue completely as
previously reported (Jiang et al., 2009). Then, the
amounts of protein were determined by BCA kit (Pierce,
USA).
The levels of ERK1/2 phosphorylation (p-ERK1/2) and
protein expression were determined using WB as
described previously (Zhang et al., 2007). Samples containing an equal amount of total protein were loaded on
10% SDS-PAGE gel. After transferring to nitrocellulose
membranes (Schleicher & Schuell, USA), unspecific
binding was blocked by incubating in blocking buffer for
1 hr. The blots were then incubated with primary antibodies overnight at 4 C. The following antibodies at a
1:1,000 dilution were used: rabbit anti-mouse p-ERK1/2,
rabbit anti-mouse total ERK1/2 (T-ERK1/2, Promega,
USA), or mouse anti-b-actin (Sigma, USA). After incubating with an anti-rabbit or anti-mouse horseradish
peroxidase-conjugated secondary antibody, protein was
visualized using ECL-plus Kit (PerkinElmer Life Science, USA).
Data Analysis
Data were presented as mean SD (standard deviation). Statistical analysis was conducted by one-way
analysis of variance (ANOVA) followed by individual
post hoc multiple comparisons. A statistical difference
was accepted as significant at P < 0.05.
RESULTS
Effects of CFA Injection and TENS Application
on Thermal Hyperalgesia of Rats
CFA injection produced an area of localized swelling,
erythema, and hypersensitivity to thermal stimuli,
which persisted for the duration of experiment (48 hr).
As shown in Table 2, the response time of HPL to thermal stimuli of CFA-injected rats at 1 hr decreased significantly (P < 0.05, N ¼ 6) when compared with that of
control group. However, TENS application could increase
the response time of HPL both in control and CFA injection groups significantly (#P < 0.05, N ¼ 6).
Effects of CFA Injection and TENS Application
on c-Fos Expression in the Spinal Dorsal
Horn, the SI Area of Cortex, and the
Amygdala of Rats
As shown in Fig. 1A, c-Fos protein expressed in the
ipsilateral laminae I and II of the spinal dorsal horn,
the contralateral SI area of cortex, and the amygdala.
The numbers of c-Fos positive neurons in the ipsilateral spinal dorsal horn, the contralateral SI area of
cortex, and the amygdala increased significantly at 1
hr post CFA injection (P < 0.05, N ¼ 6, Fig. 1B and E).
In addition, 20 min TENS stimulation also increased
c-Fos protein expression significantly in the ipsilateral
spinal dorsal horn, the contralateral SI, and the
1210
YANG ET AL.
Fig. 1. Effects of CFA injection and TENS application on c-Fos
expressions in ipsilateral spinal dorsal horn, contralateral SI area of
cortex, and amygdala of rats. Typical results of c-Fos immunostaining
in the ipsilateral laminae I and II of the spinal dorsal horn, contralateral
SI area of cortex, and amygdala of rats following injections of saline
solution and sham transcutaneous electrical nerve stimulation (TENS,
A), complete Freund’s adjuvant (CFA, B), TENS application (C), and
TENS at 0.5 hr post CFA (D). *P < 0.05 versus control group, #P <
0.05 versus CFA-treated group, N ¼ 6 per group.
amygdala (Fig. 1C and E). However, 20 min TENS
stimulation started at 0.5 hr post CFA injection could
reduce the number of c-Fos positive neurons in the ipsilateral spinal dorsal horn, but not in the contralateral SI area of cortex and the amygdala, when
compared with that of CFA group at 1 hr post CFA
injection (Fig. 1D and E).
Effects of CFA Injection and TENS Application
on ERK1/2 Phosphorylation and Protein
Expression Levels in the Spinal Dorsal Horn,
the SI Area of Cortex, and the Amygdala of Rats
The representative immunoblotting results of p-ERK1/
2 and T-ERK1/2 were shown in Fig. 2A (ipsilateral
TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION
1211
Fig. 2. Typical Western blot results showed the changes in ERK1/2
phosphorylation and protein expression in ipsilateral spinal dorsal horn
(A), contralateral SI area of cortex (B), and amygdala (C) of rats following CFA and TENS. ERK1/2 and b-actin were detected at 42/44 and
43 kDa, respectively. Control, saline solution, and sham TENS;
P-0.5 hr, 0.5 hr post CFA; P-1 hr, 1 hr post CFA; P-2 hr, 2 hr post
CFA; P-24 hr, 24 hr post CFA; P-48 hr, 48 hr post CFA; P-0.5 hr þ
TENS, 20 min TENS at 0.5 hr post CFA; P-24 hr þ TENS, 20 min
TENS at 24 hr post CFA.
spinal dorsal horn), B (contralateral SI area of cortex),
and C (contralateral amygdala). The bands of p-ERK1/2,
T-ERK1/2 as well as b-actin could be detected at 44 kDa
for ERK1, 42 kDa for ERK2, and 43 kDa for b-actin,
respectively. As shown in Fig. 3A, the phosphorylation
levels of ERK2, not ERK1, at 0.5 hr (118.9 5.2), 1 hr
(115.2 5.4), 2 hr (128.6 8.4), 24 hr (123.1 4.6), and
48 hr (125.1 3.6) post CFA injection in ipsilateral spinal dorsal horn increased significantly (P < 0.05) when
compared with that of control group (100%, N ¼ 6 per
group). However, TENS application could inhibit the
increase of ERK2 phosphorylation in the ipsilateral spinal dorsal horn at 0.5 hr (105.7 4.6 vs. P-30 min, P <
0.05) and 24 hr (108.5 4.2 vs. P-24 h, P < 0.05) post
CFA injection.
Similarly, there were significant increase of ERK2
phosphorylation both in contralateral SI (Fig. 2B and
3B) and amygdala (Fig. 2C and 3C) at 0.5 hr, 1 hr, 2 hr,
24 hr, and 48 hr post CFA injection. TENS application
abolished the increase of ERK2 phosphorylation of CFAinjected rats (Fig. 2B, 2C, 3B and 3C). In addition, no
changes of total ERK1/2 protein expressions were
detected in the ipsilateral spinal dorsal horn, the contralateral SI area, and the amygdala of rats following CFA
injection (data not shown).
Fig. 3. Quantitative analysis of ERK1/2 phosphorylation level in ipsilateral spinal dorsal horn (A), and contralateral SI area of cortex (B),
and amygdala (C) of rats following CFA and TENS. Fifty-four rats were
randomly divided into the following nine groups: control (N ¼ 6), P-0.5
hr (N ¼ 6), P-1 hr (N ¼ 6), P-2 hr (N ¼ 6), P-24 hr (N ¼ 6), P-48 hr
(N ¼ 6), P-0.5 hr þ TENS (N ¼ 6) and P-24 hr þ TENS (N ¼ 6). The
results showed that TENS application suppressed CFA-induced ERK2
activation in the ipsilateral spinal cord, contralateral SI area of cortex,
and amygdala of rats. *P < 0.05 versus control.
DISCUSSION
In this study, we undertook a detailed analysis on cFos protein expression and ERK1/2 phosphorylation levels in the spinal dorsal horn, the SI area of cortex, and
the amygdala of rats in response to CFA injection and
TENS stimulation. Our results demonstrated that CFA
injection in ankle of rat in vivo causes significant c-Fos
expressions as well as ERK2 activation. The application
of TENS stimulation on KI 1 could block the increases of
c-Fos expression and ERK2 phosphorylation as well as
an obvious analgesia, which could be detected via the
increased response time of HPL in rats under thermal
stimuli.
Ji et al. (Ji et al., 1999; 2002) found that CFA injection
of hind paw produced a persistent inflammation and a
1212
YANG ET AL.
sustained ERK activation in neurons of the superficial
dorsal horn. Zhuang et al. (Zhuang et al., 2005) reported
that fifth lumbar spinal nerve ligation induced an immediate (<10 min) but transient (<6 hr) induction of ERK
phosphorylation restricted to neurons in the superficial
dorsal horn. These findings suggested that the involvement of p-ERK in peripheral inflammatory pain hypersensitivity may be contributed to the regulation of target
genes such as IEGs. In this study, we found that CFA
induced a persistent ERK2 activation (>48 hr) not only
in the spinal cord but also in the SI area of cortex and
the amygdala.
Our data also provided evidence that CFA injection
causes an obvious increased expression of c-Fos in the
spinal cord, the SI area of cortex, and the amygdala of
rats. c-Fos is a very important IEGs member, which has
been shown to take part in injury-related cellular mechanisms in many different systems including neuronal
transport blockade (Guo et al., 2004; Wang et al., 2006).
c-Fos induction by CFA had already been demonstrated
in neurons of the spinal cord and cortex (Abbadie et al.,
1994; Bellavance and Beitz, 1996; Cruz et al., 2007).
Furthermore, we found that CFA injection induced c-Fos
expressions in the amygdala. Amygdala is a complex
subcortex structure, which mediates a specific aspect of
emotional behaviors including the process of pain encoding and modulation. Studies have demonstrated that the
amygdala has abundant opiates receptors and participates in both opioid analgesia and acupuncture analgesia (Fields, 2000; Napadow et al., 2007). The increases of
c-Fos expression and ERK2 phosphorylation in the
amygdala suggested that it may integrate the nociceptive information from the spinal cord and other cortical
areas and then generate the emotional and behavioral
responses on pain.
Another important finding of this study is that TENS
application on KI 1 could inhibit CFA-induced ERK2
activation and c-Fos expression. c-Fos and ERK expressions were reduced by ERK inhibitor in CFA-treated
rats implicated the important role for ERK/c-Fos-dependent transduction pathways in acute and chronic
modulation of nociceptive stimulation (Giles et al.,
2007). In addition, TENS on acupoint induced an
obvious analgesic effect by the increased HPL of CFAtreated rats. TENS has been used to promote analgesia
for nearly 40 years. However, the use of TENS combined
with acupoint has not been widespread despite of its
prominent improvement in function of the affected
region especially at pain relieving. Studies supported the
hypothesis that therapeutic acupuncture was mediated
by opioidergic and/or monoamingergic neurotransmission involving the brain stem, the thalamus, and the
amygdala action (Garrison and Foreman, 1994; Dhond
et al., 2007). Afferent spinal gating and the diffuse noxious inhibitory control may be involved in short-term analgesic effects of TENS stimulation (Carlsson, 2002).
Our primary fMRI study demonstrated that the brain
network associated with the amygdala implicated in
both pain sensation and pain modulation, and acupuncture might change this amygdala-specific brain network
into a functional state to affect pain perception and pain
modulation (Qin et al., 2008).
In conclusion, these findings suggest that down-regulation of ERK2 phosphorylation and c-Fos expression in
the spinal dorsal horn as well as in the SI area of cortex
and the amygdala were involved in TENS inhibition on
CFA-induced thermal hyperalgesia of rats. It also provide a reasonable explanation for the actual analgesic
effect of acupuncture as well as direct evidence against
that an acupuncture point may have its own functional
specificity. However, further experiment on the mechanism of TENS-induced dephosphorylation of ERK after
CFA stimulation should be carried out.
ACKNOWLEDGMENTS
The authors thank Dr. Shewei Guo, Dr. Hao Wang,
Dr. Chengji Liu, and Dr. Xiangning Bu for technical assistance. They are grateful to Professors Junfa Li, Ming
Zhang, Deshan Zhou, and Weiming Duan for reading
and commenting earlier drafts of this article. Authors
also thank all participants for their time and patience.
LITERATURE CITED
Abbadie C, Besson JM, Calvino B. 1994. C-Fos expression in the
spinal-cord and pain-related symptoms induced by chronic arthritis in the rat are prevented by pretreatment with freund adjuvant. J Neurosci 14:5865–5871.
Bellavance LL, Beitz AJ. 1996. Altered c-fos expression in the parabrachial nucleus in a rodent model of CFA-induced peripheral
inflammation. J Comp Neurol 366:431–447.
Bjordal JM, Johnson MI, Ljunggreen AE. 2003. Transcutaneous
electrical nerve stimulation (TENS) can reduce postoperative
analgesic consumption. A meta-analysis with assessment of optimal treatment parameters for postoperative pain. Eur J Pain
7:181–188.
Buchel C, Dolan RJ. 2000. Classical fear conditioning in functional
neuroimaging. Curr Opin Neurobiol 10:219–223.
Carlsson C. 2002. Acupuncture mechanisms for clinically relevant
long-term effects—reconsideration and a hypothesis. Acupunct
Med 20:82–99.
Chao AS, Chao A, Wang TH, Chang YC, Peng HH, Chang SD, Chao
A, Chang CJ, Lai CH, Wong AM. 2007. Pain relief by applying
transcutaneous electrical nerve stimulation (TENS) on acupuncture points during the first stage of labor: a randomized doubleblind placebo-controlled trial. Pain 127:214–220.
Cruz CD, Ferreira D, McMahon SB, Cruz F. 2007. The activation of
the ERK pathway contributes to the spinal c-fos expression
observed after noxious bladder stimultion. Somatoens Mot Res
24:15–20.
Dhond RP, Kettner N, Napadow V. 2007. Do the neural correlates of
acupuncture and placebo effects differ? Pain 128:8–12.
Fields HL. 2000. Pain modulation: expectation, opioid analgesia and
virtual pain. Prog Brain Res 122:245–253.
Garrison DW, Foreman RD. 1994. Decreased activity of spontaneous
and noxiously evoked dorsal horn cells during transcutaneous
electrical nerve stimulation (TENS). Pain 58:309–315.
Giles PA, Trezise DJ, King AE. 2007. Differential activation of protein kinases in the dorsal horn in vitro of normal and inflamed
rats by group I metabotropic glutamate receptor subtypes. Neuropharmacology 53:58–70.
Guo ZL, Moazzami AR, Longhurst JC. 2004. Electroacupuncture
induces c-Fos expression in the rostral ventrolateral medulla and
periaqueductal gray in cats: relation to opioid containing neurons.
Brain Res 1030:103–115.
Han JS. 2003. Acupuncture: neuropeptide release produced by electrical stimulation of different frequencies. Trends Neurosci 26:
17–22.
Hargreaves K, Dubner R, Brown F, Flores C, Joris J. 1988. A new
and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32:77–88.
Hay CH, Trevethick MA, Wheeldon A, Bowers JS, de Belleroche JS.
1997. The potential role of spinal cord cyclooxygenase-2 in the
TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION
development of Freund’s complete adjuvant-induced changes in
hyperalgesia and allodynia. Neuroscience 78:843–850.
Ji RR, Baba H, Brenner GJ, Woolf CJ. 1999. Nociceptive-specific
activation of ERK in spinal neurons contributes to pain hypersensitivity. Nat Neurosci 2:1114–1119.
Ji RR, Befort K, Brenner GJ, Woolf CJ. 2002. ERK MAP kinase
activation in superficial spinal cord neurons induces prodynorphin
and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity. J Neurosci 22:478–485.
Jiang J, Yang W, Huang P, Bu X, Zhang N, Li J. 2009. Increased
phosphorylation of Ets-like transcription factor-1 in neurons of
hypoxic preconditioned mice. Neurochem Res 34:1443–1450.
Kawasaki Y, Kohno T, Zhuang ZY, Brenner GJ, Wang H, Van Der
MC, Befort K, Woolf CJ, Ji RR. 2004. Ionotropic and metabotropic
receptors, protein kinase A, protein kinase C, and Src contribute
to C-fiber-induced ERK activation and cAMP response elementbinding protein phosphorylation in dorsal horn neurons, leading
to central sensitization. J Neurosci 24:8310–8321.
Kim JH, Chung JY, Kwon YK, Kim KJ, Yang CH, Hahm DH, Lee
HJ, Pyun KH, Shim I. 2005. Acupuncture reduces alcohol withdrawal syndrome and c-Fos expression in rat brain. Am J Chin
Med 33:887–896.
Kim JH, Kim HK, Park YI, Sohn IC, Choi DO, Kim MS, Park BR.
2006. Moxibustion at ST36 alleviates pain in complete Freund’s
adjuvant-induced arthritic rats. Am J Chin Med 34:57–67.
Kwon YB, Han HJ, Beitz AJ, Lee JH. 2004. Bee venom acupoint
stimulation increases Fos expression in catecholaminergic neurons in the rat brain. Mol Cells 17:329–333.
Lu R, Liu M. 1991. Clinical application of single acupoint for treatment. J Tradit Chin Med 11:284–285.
McCarson KE, Krause JE. 1994. NK-1 and NK-3 type tachykinin
receptor mRNA expression in the rat spinal cord dorsal horn is
increased during adjuvant or formalin-induced nociception.
J Neurosci 14:712–720.
Napadow V, Kettner N, Liu J, Li M, Kwong KK, Vangel M, Makris
N, Audette J, Hui KK. 2007. Hypothalamus and amygdala
response to acupuncture stimuli in Carpal Tunnel Syndrome.
Pain 130:254–266.
1213
Petrovic P, Carlsson K, Petersson KM, Hansson P, Ingvar M. 2004.
Context-dependent deactivation of the amygdala during pain.
J Cogn Neurosci 16:1289–1301.
Petrovic P, Petersson KM, Ghatan PH, Stone-Elander S, Ingvar M.
2000. Pain-related cerebral activation is altered by a distracting
cognitive task. Pain 85:19–30.
Petrovic P, Petersson KM, Hansson P, Ingvar M. 2002. A regression
analysis study of the primary somatosensory cortex during
pain10. Neuroimage 16:1142–1150.
Qin W, Tian J, Bai L, Pan X, Yang L, Chen P, Dai J, Ai L, Zhao B,
Gong Q, Wang W, von Deneen KM, Liu Y. 2008. FMRI connectivity analysis of acupuncture effects on an amygdala-associated
brain network. Mol Pain 4:1–17.
Roh DH, Kim HW, Yoon SY, Kang SY, Kwon YB, Cho KH, Han HJ,
Ryu YH, Choi SM, Lee HJ, Beitz AJ, Lee JH. 2006. Bee venom
injection significantly reduces nociceptive behavior in the
mouse formalin test via capsaicin-insensitive afferents. J Pain
7:500–512.
Wang TT, Yuan WL, Ke Q, Song XB, Zhou X, Kang Y, Zhang HT,
Lin Y, Hu YL, Feng ZT, Wu LL, Zhou XF. 2006. Effects of electroacupuncture on the expression of c-jun and c-fos in spared
dorsal root ganglion and associated spinal laminae following removal of adjacent dorsal root ganglia in cats. Neuroscience
140:1169–1176.
Woolf CJ. 2007. Central sensitization: uncovering the relation
between pain and plasticity. Anesthesiology 106:864–867.
Woolf CJ, Salter MW. 2000. Neuronal plasticity: increasing the gain
in pain. Science 288:1765–1769.
Zhang N, Gao G, Bu X, Han S, Fang L, Li J. 2007. Neuron-specific
phosphorylation of c-Jun N-terminal kinase increased in the brain
of hypoxic preconditioned mice. Neurosci Lett 423:219–224.
Zhang YQ, Ji GC, Wu GC, Zhao ZQ. 2003. Kynurenic acid enhances
electroacupuncture analgesia in normal and carrageenan-injected
rats. Brain Res 966:300–307.
Zhuang ZY, Gerner P, Woolf CJ, Ji RR. 2005. ERK is sequentially
activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. Pain 114:149–159.
Документ
Категория
Без категории
Просмотров
4
Размер файла
401 Кб
Теги
expressions, acupoint, hyperalgesia, erk2, thermal, yongquan, induced, nerve, cfa, electric, regulation, reduced, stimulating, fos, downs, phosphorylation, transcutaneous, rats, via
1/--страниц
Пожаловаться на содержимое документа