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Pain Medicine 2013; 14: 19441953

Wiley Periodicals, Inc.

Peripheral Nerve Adjustment for Postherpetic

Neuralgia: A Randomized, Controlled
Clinical Study

*Department of Anesthesiology, Shanghai Sixth

Peoples Hospital, Shanghai JiaoTong University,
Shanghai;

College of Pharmacy, Anhui Medical University,

Heifei, China

Reprint requests to: Wei Jiang, PhD, Department of

Anesthesiology, Shanghai Sixth Peoples Hospital,
Shanghai JiaoTong University, 600 Yi-Shan Road,
Shanghai 200233, China. Tel: +86-21-64369181;
Fax: +86-21-64368920; E-mail: jiangw@sjtu.edu.cn.
Conflicts of interest: There are no conflicts of interest.

than in the control groups A and C following treatment (P < 0.05). In addition, the QOL and SF-36
scores for group B improved substantially following
treatment compared to groups A and C, and this
effect was maintained up to 180 days after treatment
(P < 0.05). The average dosage of pain medication
was also lower in group B, compared to groups A
and C, following treatment (P < 0.05).
Conclusions. We conclude that peripheral nerve
adjustment can relieve PHN pain and improve
patients quality of life. The possible mechanisms
involved may include the reduction of both peripheral and central sensitization, the modulation of
nerve plasticity, and an increase in endogenous
analgesic molecules.
Key Words. Peripheral Nerve; Postherpetic Neuralgia; Sensitization; Plasticity

Authors contributed equally to this work.

Clinical Trials registration number: ISRCTN58767633.

Abstract
Objective. To observe the therapeutic effect of
peripheral nerve adjustment for the treatment of
postherpetic neuralgia (PHN).
Methods. One hundred and two patients with PHN
were randomly assigned to three groups; the control
group (A), the experimental group (B), which was
subjected to peripheral nerve adjustment, and
patients who received a sham peripheral nerve
adjustment, thus serving as a positive control group
(C). The patients Visual Analogue Scale (VAS) and
total oral rescue dosage for pain management were
recorded at days 1, 3, 7, 14, and 28 following
treatment. Quality of life (QOL), 36-Item ShortForm Health Survey (SF-36), and side effects were
recorded following treatment.
Results. We observed that the average VAS score
was significantly lower in the treatment group (B)
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Introduction
Postherpetic neuralgia (PHN) is a condition in which the
individual experiences chronic pain as a consequence of
nerve damage resulting from a herpes zoster (HZ) virus
infection (also known as shingles). Pain often begins after
peripheral nerve damage has occurred, and persists anywhere from 3 months to many years after the resolution of
the HZ rash [1]. PHN affects a significant proportion of HZ
patients, with the elderly being the most vulnerable. PHN
can have a severe impact on the patients quality of life
and ability to function normally. The health care costs
related to persistent PHN are huge, and can place a heavy
economic burden and stress on both the family and
society as a whole [2].
Unfortunately, PHN is often refractory to existing treatments. On the basis of the pathophysiological characteristics of this condition, numerous treatments have been
applied in the clinic. Conventional treatments, including
antidepressants, antiepileptic drugs, and opioids have
been in use for a number of years. Pregabalin and several
novel topical patches, containing lidocaine or capsaicin,
have also been used. More invasive treatments, such as

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Ke Ma, PhD,* Quan-hong Zhou, PhD,*

Yong-ming Xu, MD,* Tao Xu, PhD,* Dong-ping Du,
PhD,* Xiaohui Huang, PhD, and Wei Jiang, PhD*

Peripheral Nerve Adjustment Reduces PHN Pain

nerve blockage, chemically induced nerve damage, and
surgical treatment (spinal cord stimulation, peripheral
nerve stimulation) have also been applied. Recently, a HZ
vaccine was found to be effective under certain conditions
[3]. Despite varying degrees of success, these treatments
have provided an effective cure for all cases of PHN.
Indeed, some researchers have denoted PHN to be a
never-ending challenge [4].

Methods
Participants
Our experimental protocol was approved by the Human
Ethics Committee of the Shanghai 6th Municipal Hospital.
The current study was conducted in accordance with the
Ethical Guidelines for Pain Research in Humans and consisted of a prospective, randomized, controlled, and
single-blind clinical trial that took place between September 2007 and December 2009. This trial was registered
with controlled-trials.com, number ISRCTN58767633.
Consent forms were signed by patients before they were
recruited into the study. The nerve sectors most often
affected in PHN are the thoracic nerves, which are implicated in over 50% of all PHN cases. Therefore, this study

Interventions
One hundred and two patients were enrolled in the study
and were randomly assigned into three groups. Group A,
the blank control group, received disinfectant onto the
affected skin region without further peripheral nerve adjustment. Group B, the treatment group, received peripheral
nerve adjustment under the region of skin affected by PHN,
which was demarcated according to the self-reporting of
the patient. Peripheral nerve adjustment was effected as
follows: a number 4 cannular needle was inserted under the
skin, with the tip of the needle located underneath the most
painful region. The base of the needle was fixed as the
center of a circle whose radius equaled the needles length.
The needle was moved clockwise 22.5 degrees, and then
counterclockwise 22.5 degrees (a total of 45 degrees). The
needle was rotated in this way at a rate of one 45-degree
cycle/sec for 3 minutes. The needle was then removed,
leaving the cannula, which remained under the skin for 24
hours (Figure 1). In group C, the positive control group,

Figure 1 The method of peripheral nerve adjustment. A number 4 cannular needle was inserted under the
skin.The needle was moved clockwise 22.5 degrees, and then counterclockwise 22.5 degrees (a total of 45
degrees). The needle was rotated in this way at a rate of one 45-degree cycle/sec for 3 minutes. The needle
was then removed, leaving the cannula, which remained under the skin for 24 hours.
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Traditional Chinese acupuncture has been shown to be

valuable in the treatment of PHN [5,6] and has the advantages of being simple to perform, having little systemic
effect, and few side effects. Therefore, we applied a particular technique, termed peripheral nerve adjustment,
which was originally accomplished by use of the fu
needle [7] (Patent Number: ZL97114318.8), to the treatment of PHN. To further observe the effect of peripheral
nerve adjustment on PHN, we designed a randomized,
controlled, single-blind study.

focused on PHN patients whose painful area was located

at T4-T12. Patients who were between 60 and 90 years of
age, and whose PHN history was longer than 6 months
(ranging from 6 months to 8 years) were eligible for the
current study. Other inclusion criteria included PHN that
had been refractory to conventional treatments according
to International Association for the Study of Pain guidelines (such as antiepileptic medicine, antidepressants,
opioids, and physical treatments), and a visual analogue
scale (VAS) greater than 3 (010 scale). Exclusion
criteria included intolerance to the study, uncooperative
behavior, and the inability to finish the self-evaluation
questionnaires, which included the VAS, the Quality
of Life Scale (QOL), and the Short Form (36) Health
Survey (SF-36).

Ma et al.
following routine skin disinfection, a cannular needle was
inserted under the skin, but no nerve adjustment was
made. An attending physician ran one finger over the skin,
so as to mimic the waving movement of the needle in the
treatment group (i.e., clockwise for 22.5 degrees and then
counterclockwise for 22.5 degrees) at the same rate as in
the treated group (one finger movement/sec for 3 minutes).
The needle was removed and the cannula was left under
the skin for 24 hours. All three groups were treated
twice a week for 3 weeks, and followed up for 180 days
(Figure 2).
Appendices: Introduction of Persipheral
Nerve Adjustment

1. Analgesic efficacy (VAS): VAS scores were evaluated

before treatment and on days 1, 3, 7, 14, and 28
following treatment (approximately 810 AM each day).
2. QOL: A patient satisfaction scale (PSS) was evaluated
prior to treatment and on days 28, 60, 90, and 180
following treatment. The PSS asked the patient to rate
his/her satisfaction on a 010 scale, with 0 as very
dissatisfied and 10 as very satisfied (Single-Scale
Evaluation [Uniscale]).
3. SF-36 indices evaluation: SF-36 indices including
physical functioning, physical role, pain index, general
health perceptions, vitality, social function, emotional
role, and mental health were evaluated prior to the
treatment and on days 28, 60, 90, and 180 following treatment.
4. Total dosage of rescue medication: Tramadol
50200 mg twice a day orally was administered as

Figure 2 Study flow chart and timeline. All 112 randomized participants were included in the intention-totreat analysis by use of mixed-effects modeling that includes patients with incomplete follow-up data.
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Using the Fu acupuncture technique, we performed

peripheral nerve adjustment in accordance with the anatomical dermatological nerve distribution associated with
PHN [7] (Figure 1).

Outcome Measures

Peripheral Nerve Adjustment Reduces PHN Pain

rescue medication for pain control for patients with a
VAS score higher than 3 and with a frequency of acute
pain flares greater than 3 times per day. The average
dosages of tramadol (mg/day) received by patients
were assessed on days 1, 3, 7, 14, and 28 following
treatment in each group. To prevent gastric side
effects, metoclopramide was given at a dose of 5 mg
three times daily (t.i.d) for 3 to 7 days.
5. Side effects: Any side effects, including bleeding at the
adjustment site, infection, and increased pain, were
recorded for each group on days 1, 3, 7, 14, and 28
following treatment (Figure 2).

control groups, compared to pretreatment values (difference between groups A and B = 1.33 0.25, P < 0.0001;
between B and C = 1.39 0.26, P < 0.0001). The magnitude of the posttreatment VAS reduction was not significantly different between the control A and C groups
(0.06 0.13, P = 0.63). Our analysis of variance showed a
significant interaction between treatment group and
follow-up time (P < 0.001). This finding suggests that the
treatment effects at 28 days post-procedure were not
uniform across the different groups, likely due to the early
improvement in the VAS observed in the peripheral nerve
adjustment group B (Figure 3).

Statistical Analysis
Rescue Drug Dosage

Endpoints were analyzed by intention to treat, including all

data available from the 112 randomized patients. We used
repeated measures analysis of variance with mixed
models that assumed a Toeplitz covariance structure in
order to perform an analysis of the primary and secondary
endpoints of the full analysis set, which contained unbalanced data. A P value less than 0.05 was considered to
be statistically significant. Analyses were performed using
SAS PROC Mixed, V9.13 software (SAS Institute, Cary,
NC, USA).
Results
Patient Demography
Patients demographic characteristics had no significant
effect upon our findings (Table 1).
VAS
Following treatment, the VAS was decreased to a greater
extent in the treatment B group compared to either of the

The rescue drug dosage (mg) per day was lower in the
treatment group B compared to groups A and C following
treatment. The magnitude of the post-treatment decrease
in rescue drug dosage was greater for the treated B group
compared to the A or C control groups (difference
between A and B = 64.88 12.51, P < 0.0001, between
B and C = 42.97 11.58, P < 0.0001). We also found a
significant difference between the magnitude of rescue
drug decrease following treatment between groups C and
A (21.91 11.46, P = 0.0003). We found a significant
interaction between treatment condition and follow-up
time (P < 0.001); this interaction suggests that the rescue
drug dosage was not uniform across the different groups
at follow-up due to a stable level of rescue drug dosage
among the three groups on days 14 and 28 (Figure 3).
QOL (PSS)
The PSS showed a greater improvement following treatment in group B compared to the untreated groups A
and C (B vs A = 1.17 points 0.15, P < 0.001; B vs
C = 1.06 points 0.16, P < 0.001). There was no significant difference in the magnitude of PSS changes
between groups A and C (A vs C = 0.11 points 0.07,
P = 0.15). As with the other measurements, we
observed a significant interaction between treatment
condition and follow-up time (P < 0.001), reflecting the
fact that the magnitude of PSS improvement was larger
on days 28 and 60 following treatment than on days 90
and 180 (Figure 3).

Table 1 Baseline characteristics of the study participants

Patient

Group A
N = 34 (Completed 33)

Group B
N = 34 (Completed 31)

Group C
N = 34 (Completed 31)

Male/Female
Age (years)
Left/right (T4-12)
Weight (Kg)
Pain duration (months)

22/12 (22/11)
71.6 12.7 (71.1 12.3)
17/17 (16/17)
70.3 11.2 (68.9 10.5)
28.9 18.5 (29.6 17.3)

16/18 (14/17)
68.4 14.4 (70.6 13.5)
20/14 (19/12)
68.6 9.6 (69.4 10.4)
22.1 11.9 (24.9 13.4)

20/14 (20/11)
70.5 12.2 (73.9 13.7)
16/18 (13/18)
72.5 13.1 (73.7 11.2)
25.2 16.6 (24.4 14.2)

Group A = blank control; Group B = treatment with peripheral nerve adjustment; Group C = positive control.
Data are mean SD or numbers.

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According to our pilot study, the effectiveness rate of

peripheral nerve adjustment in the treatment group was
70%, compared to 20% in the positive control group.
Therefore, the difference between the effectiveness of
treatment rates in the two groups was 50%. We then
calculated the estimated sample number to be 23 in each
group, which provides 80% power and a level of statistical
significance of 0.05 ( = 0.05). Quantitative data are presented as mean SD.

Ma et al.

SF-36
The SF-36 index scores reflecting general health, social
function, emotional roles, and mental health all showed
significant improvement following treatment in group B.
The magnitude of improvement was significantly greater
than that observed following treatment in groups A and C
(P < 0.05). The magnitude of the general health score
improvement differed by 6.29 points 2.23 between
groups B and A (P < 0.0001), and by 6.38 points 2.27
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between groups B and C (P < 0.0001), while the difference in general health score improvement was only 0.08
points 2.24 between groups A and C (P = 0.94). The
magnitude of the social function score improvement differed by 10.17 points 2.28 between groups B and A
(P < 0.0001), and by 9.83 points 2.31 between groups
B and C (P < 0.0001). There was no significant difference
between groups A and C (0.33 points 1.61; P = 0.77) on
the improvement of social function score. The magnitude
of the general health score improvement differed by 10.13

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Figure 3 Changes in measures of Visual Analogue Scale (VAS), rescue drug dosage, and QOL (PSS) among
the three groups. In panels VAS and rescue drug dosage, lower scores indicate improvement. For quality of
life (QOL; Patient Satisfaction Scale [PSS]) panels, higher values indicate improvement. In all panels, the
treatment P value refers to the average treatment effect difference at all follow-up time points. The treatment
vs time P value relates to time-related changes in this difference. A significant treatment by time interaction
indicates that the treatment effect difference is not stable throughout the follow-up. The VAS and QOL
showed early improvements, and the dosage of the rescue drug was lowered at early time points, and stable
later during follow-up time at three groups.

Peripheral Nerve Adjustment Reduces PHN Pain

points 3.52 between groups B and A (P < 0.0001), and
by 9.08 points 3.56 between groups B and C
(P < 0.0001), with no significant difference observed
between groups A and C (1.05 points 3.51; P = 0.55).
The magnitude of the improvement in the mental health
index differed by 8.24 points 1.84 between groups B
and A (P < 0.0001), and by 7.18 points 1.86 between
groups B and C (P < 0.0001). We observed no significant
difference in the improvement in the mental health index
between groups A and C (1.07 points 1.85; P = 0.25).
In these measures, there were no significant interactions
between treatment condition and follow-up time in all the
three groups (Figure 4) for the indexes of physical function
(F = 0.71, P = 0.68), physical role (F = 0.34, P = 0.95),
vitality (F = 0.86, P = 0.55), or bodily pain (F = 0.49,
P = 0.86).

Apart from one case each of minor bleeding at the adjustment site in groups B and C, no patient in the study
required any additional treatment and no other side effects
were observed (data not shown).
Discussion
The results from the present study indicate that peripheral
nerve adjustment can not only effectively relieve PHNassociated pain in the short term (28 days following treatment), but that this therapy also has a long-term (180 days
after treatment) effect in terms of improved quality of life
and SF-36 index scores reflecting improved general
feeling, mental health index, social function, and emotional
roles. No adverse events were reported in the study
participants, suggesting that peripheral nerve adjustment
is a relatively safe therapy for patients with PHN.
These results are consistent with those of researchers
applying other treatment modalities such as peripheral
nerve electrical modulation, which can reduce allodynia for
an extended period of time [8]. In addition, the application
of tactile brush stimulation to the area of peripheral
allodynia has been shown to reduce the painful area by
more than 30%, an effect that lasted for several days [9].
Functional magnetic resonance imaging (fMRI) studies
have shown that several brain regions involved in cognition, motor control, and the nociception respond to even
a light brush touch in patients suffering from neuropathic
pain [10,11]. These changes reflect a manifestation of
central neural plasticity that is directly correlated to an
individuals perception of neuropathic pain [12].
Peripheral nerves and numerous central brain nuclei
interact to form a complex network that produces analgesia following peripheral nerve adjustment. This treatment therefore represents the functional integration of
the peripheral and central nervous system (CNS) to
produce a therapeutic effect [13]. Similar to traditional
Chinese medicine, the basic aim of peripheral nerve
adjustment is to eliminate or suppress the cause of ill
health and to restore the body to balanced health [5].

Peripheral nerve sensitization is very important to CNS pain

sensitization [14,15]. PHN impairs all sensory fiber groups,
such as the C, A, and A- fibers, leading to sharp pain,
burning pain, allogesia, and/or hypersensitivity, all of which
lead to central pain sensitization [16,17]. In a PHN area of
hypersensitivity, even damaged nerves retain a connection
with the CNS while also causing persistent pain and hypersensitivity [15,18]. Our findings support the concept that
the CNS is more sensitive to peripheral signals than we had
previously imagined [14]. Neuroimaging technologies such
as fMRI have shown that a needle puncture can modulate
the activity of peripheral afferent fibers [19,20], and that this
activity is propagated along the pathways of the spinal
dorsal horn and ventrolateral nerve system to ultimately
modulate the function and the activity of the CNS [20].
Activity in different regions of the CNS may then change in
order to modulate the perception of pain, leading to analgesia [13]. At the same time, this modulation may also
affect the functioning of the descending inhibitory signals
from the rostral ventromedial medulla, nucleus raphe
magnus, and limbic system (insula and anterior cingulate
cortex), to rapidly adjust the level of analgesia [13,21,22].
Another mechanism by which peripheral nerve adjustment
may have therapeutic effects is via the induction of a
series of inflammatory responses and increases in the
production of pro-inflammatory molecules [23]. Rather
than exacerbating and worsening the pain, however, the
inflammatory response induced by peripheral nerve
adjustment leads to pain relief. These results are supported by the classic combating poison with poison
philosophy in traditional Chinese medicine. For example,
scorpion venom, which typically causes pain in people,
has been used to treat pain via the blockade of sodium
channels [24]. Micro-dosages of arsenic have also been
administered to successfully combat acute promyelocytic
leukemia [25,26]. In addition, the intravenous administration of the pro-inflammatory factor prostaglandin E1 in
patients with post-herpetic neuralgia produces analgesia
for as long as 1 month [27,28]. Thus, we postulated that
these redundant inflammatory mechanisms may overload
the nerve, thus reducing its ability to transmit activity and
leading to analgesia. Even in established neuropathic pain,
nerves responsible for neuropathic pain have shown a
potential for plasticity [9]. We call this potential for plasticity
following previous plasticity as re-plasticity, which may
interfere with several changes in chemical structures and
functions [23] (Figure 5).
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Side-Effects

The fact that the treated group displayed longer and

more effective analgesia than the control groups indicates that the mechanical stimulus caused by the needle
movement is important for the effect. The simple insertion of the needle produces short-term analgesia, but the
twisting action of the needle is necessary for the prolonged analgesic effect [13]. When the cannula was
moved clockwise and counterclockwise underneath the
skin, it likely produced a mechanical stimulus that was
transferred by subcutaneous tissues and mast cells and
which interfered with both the damaged and undamaged
peripheral nerves.

Ma et al.

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Figure 4 Changes in SF-36 among the three groups. In all panels, higher scores indicate improvement. In
panels, the treatment P value refers to the average treatment effect difference during follow-up time points.
The treatment vs time P value relates to a time-related change of this difference. A significant treatment by
time interaction indicates that the treatment effect difference was not constant throughout follow-up.

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Peripheral Nerve Adjustment Reduces PHN Pain

At the same time, by a mechanism similar to that of

acupuncture analgesia, peripheral nerve adjustment also
causes an increase in adenosine triphosphate (ATP) and
endogenous opioid-like substances such as enkephalins, -endorphins, and endomorphins in the nerve
microenvironment [21,22,29]. In one research study, a
needle was inserted at the point of Zu Sanli (an acupoint)
in rats and twisted for 5 minutes, mimicking acupuncture
in the human body. The ATP production in the tissue
surrounding the needle insertion point increased 24-fold
and remained elevated for 24 hours [30]. In fact, needle
stimulation leads to ATP production and altered sodium
channel activity in the superficial skin, which contributes to
an analgesic effect [31]. Further research of peripheral
sensory mechanisms will likely contribute to additional
novel treatments for chronic pain [32].
At the molecular level, the repair of damaged nerves and
restoration of normal functioning belong to the renovation
treatment category, and will play important roles in the
future treatment of neuropathic pain [33]. We believe that
current strategies should progress from simple symptom
relief to attempts at disease modification, such as the
prevention of pain-induced neuroplasticity [34]. The
mechanisms underlying the induction of PHN are complicated, therefore multimodal treatments should be incorporated, while avoiding the repetition of a single treatment
[35]. As peripheral nerve modulation has no severe side

effects, it can be used multiple times when necessary. For

PHN patients who do not respond to conventional
medical treatment, who suffer severe side effects from
these treatments, or who refuse invasive treatments such
as spinal cord stimulation and pulsed radiofrequency
therapy, peripheral nerve adjustment could provide and
option that is likely to relieve their pain and improve their
quality of life.
In the current study, we demonstrate that peripheral nerve
adjustment has a clinical effect. However, we lack the
evidence to explore possible mechanisms underlying this
effect. For example, we were not able to compare the
function of peripheral nerve fibers before and after the
peripheral nerve adjustment treatment, as most patients
refused to undergo these more invasive tests. In addition,
we did not use fMRI to examine potential alterations in the
CNS following treatment. These shortcomings will be
addressed in future experiments using animal models,
with which we will determine the mechanisms underlying
the alleviation of pain by peripheral nerve adjustment.
Conclusion
1. Peripheral nerve adjustment can rapidly relieve PHNrelated pain and improve patients satisfaction over
the long term. This therapy is a viable option for
PHN treatment.
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Figure 5 The possible mechanisms of peripheral nerve

adjustment.
The
possible
mechanisms underlying the
peripheral nerve adjustment
include the reduction of both
peripheral and central nervous
system (CNS) sensitization,
modulation of nerve re-plasticity,
and increased levels of endogenous analgesic substances.

Ma et al.
2. The possible mechanisms underlying this pain reduction include the reduction of both peripheral and CNS
sensitization, modulation of nerve re-plasticity, and
increased levels of endogenous analgesic substances.
Further research is merited.
Acknowledgments

References
1 Sampathkumar P, Drage LA, Martin DP. Herpes
zoster (shingles) and postherpetic neuralgia. Mayo Clin
Proc 2009;84:27480.
2 Doth AH, Hansson PT, Jensen MP, et al. The burden
of neuropathic pain: A systematic review and metaanalysis of health utilities. Pain 2010;149:33844.
3 Sanford M, Keating GM. Zoster vaccine (Zostavax): A
review of its use in preventing herpes zoster and
postherpetic neuralgia in older adults. Drugs Aging
2010;27:15976.
4 Niv D, Maltsman-Tseikhin A. Postherpetic neuralgia:
The never-ending challenge. Pain Pract 2005;5:327
40.
5 Tang JL, Liu BY, Ma KW. Traditional Chinese medicine. Lancet 2008;372:193840.
6 Han JS. Acupuncture research is part of my life. Pain
Med 2009;10:6118.
7 Fu ZH, Wang JH, Sun JH, et al. Fus subcutaneous
needling: Possible clinical evidence of the subcutaneous connective tissue in acupuncture. J Altern
Complement Med 2007;13:4751.
8 Nilsson HJ, Schouenborg J. Differential inhibitory
effect on human nociceptive skin senses induced
by local stimulation of thin cutaneous fibers. Pain
1999;80:10312.
9 Love-Jones SJ, Besson M, Steeds CE, et al. Homotopic stimulation can reduce the area of allodynia in
patients with neuropathic pain. Eur J Pain 2009;13:
9428.
1952

11 Schweinhardt P, Glynn C, Brooks J, et al. An fMRI

study of cerebral processing of brush-evoked
allodynia in neuropathic pain patients. Neuroimage
2006;32:25665.
12 Latremoliere A, Woolf CJ. Central sensitization: A
generator of pain hypersensitivity by central neural
plasticity. J Pain 2009;10:895926.
13 Zhao ZQ. Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 2008;85:355
75.
14 Oaklander AL. The density of remaining nerve endings
in human skin with and without postherpetic neuralgia
after shingles. Pain 2001;92:13945.
15 Campbell JN, Meyer RA. Mechanisms of neuropathic
pain. Neuron 2006;52:7792.
16 Sakai T, Tomiyasu S, Yamada H, et al. Evaluation of
allodynia and pain associated with postherpetic neuralgia using current perception threshold testing. Clin J
Pain 2006;22:35962.
17 Truini A, Galeotti F, Haanpaa M, et al. Pathophysiology of pain in postherpetic neuralgia: A clinical and
neurophysiological study. Pain 2008;140:405
10.
18 Baron R. Mechanisms of disease: Neuropathic
painA clinical perspective. Nat Clin Pract Neurol
2006;2:95106.
19 Asghar AU, Green G, Lythgoe MF, et al. Acupuncture
needling sensation: The neural correlates of deqi using
fMRI. Brain Res 2010;1315:1118.
20 Qin W, Tian J, Bai L, et al. FMRI connectivity analysis
of acupuncture effects on an amygdala-associated
brain network. Mol Pain 2008;4:55.
21 Wang SM, Kain ZN, White P. Acupuncture analgesia:
I. The scientific basis. Anesth Analg 2008;106:602
10.
22 Wang SM, Kain ZN, White PF. Acupuncture analgesia:
II. Clinical considerations. Anesth Analg 2008;106:
61121.
23 Woolf CJ, Salter MW. Neuronal plasticity: Increasing
the gain in pain. Science 2000;288:17659.
24 Bai ZT, Liu T, Pang XY, et al. Suppression by intrathecal BmK IT2 on rat spontaneous pain behaviors and
spinal c-Fos expression induced by formalin. Brain
Res Bull 2007;73:24853.

Downloaded from http://painmedicine.oxfordjournals.org/ by guest on January 14, 2016

We express our thanks for the grants from Shanghai

JiaoTong University scientific research funding, Shanghai
Education Committee scientific research funding [No
11YZ56] and Science and Technology Commission of
Shanghai Municipal [No 12ZR1419900]. The sponsor of
the study did not participate in data collection, data analysis, data interpretation, or writing of the report. We thank
all the patients who participated in the study. We thank the
data and safety monitoring board members and Dr.
WANG Kun, for his insightful suggestions concerning the
study protocol; the Clinical Research Center nurses,
TANG Guohua and CHENG Yueping for their help with
various aspects of the study.

10 Maihofner C, Handwerker HO, Birklein F. Functional

imaging of allodynia in complex regional pain syndrome. Neurology 2006;66:7117.

Peripheral Nerve Adjustment Reduces PHN Pain

25 Hu J, Liu YF, Wu CF, et al. Long-term efficacy and
safety of all-trans retinoic acid/arsenic trioxide-based
therapy in newly diagnosed acute promyelocytic
leukemia. Proc Natl Acad Sci U S A 2009;106:
33427.
26 Zhang XW, Yan XJ, Zhou ZR, et al. Arsenic trioxide
controls the fate of the PML-RARalpha oncoprotein by
directly binding PML. Science 2010;328:2403.
27 Kanai A, Osawa S, Suzuki A, et al. Effectiveness of
prostaglandin E1 for the treatment of patients with
neuropathic pain following herpes zoster. Pain Med
2007;8:3640.

32 Argoff CE. Topical agents for the treatment of

chronic pain. Curr Pain Headache Rep 2006;10:119.
33 Christo PJ, Hobelmann G, Maine DN. Post-herpetic
neuralgia in older adults: Evidence-based approaches
to clinical management. Drugs Aging 2007;24:119.
34 Costigan M, Scholz J, Woolf CJ. Neuropathic pain: A
maladaptive response of the nervous system to
damage. Annu Rev Neurosci 2009;32:132.
35 Binder A, Baron R. Postherpetic neuralgiaFighting
pain with fire. Lancet Neurol 2008;7:10778.
Supporting Information

29 Han JS. Acupuncture and endorphins. Neurosci Lett

2004;361:25861.
30 Goldman N, Chen M, Fujita T, et al. Adenosine A1
receptors mediate local anti-nociceptive effects of
acupuncture. Nat Neurosci 2010;13:8838.

Additional Supporting Information may be found in the

online version of this article at the publishers web-site:
Supporting Information Method of peripheral nerve
adjustment.

1953

Downloaded from http://painmedicine.oxfordjournals.org/ by guest on January 14, 2016

28 Kanai A, Wang G, Hoshi K, et al. Effects of intravenous

prostaglandin E1 on pain and body temperature in
patients with post-herpetic neuralgia. Pain Med
2010;11:60916.

31 Zhao P, Barr TP, Hou Q, et al. Voltage-gated sodium

channel expression in rat and human epidermal
keratinocytes: Evidence for a role in pain. Pain
2008;139:90105.