International Journal of Neuroscience

ISSN: 0020-7454 (Print) 1543-5245 (Online) Journal homepage: http://www.tandfonline.com/loi/ines20

Effects of High-Frequency Repetitive Transcranial

Magnetic Stimulation on Reducing Hemiplegic
Shoulder Pain in Patients with Chronic Stoke: A
Randomized Controlled Trial

Gyu-sik Choi & Min Cheol Chang

To cite this article: Gyu-sik Choi & Min Cheol Chang (2017): Effects of High-Frequency Repetitive
Transcranial Magnetic Stimulation on Reducing Hemiplegic Shoulder Pain in Patients with
Chronic Stoke: A Randomized Controlled Trial, International Journal of Neuroscience, DOI:
10.1080/00207454.2017.1367682

To link to this article: http://dx.doi.org/10.1080/00207454.2017.1367682

Accepted author version posted online: 12

Aug 2017.

Submit your article to this journal

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

http://www.tandfonline.com/action/journalInformation?journalCode=ines20

Download by: [Australian Catholic University] Date: 15 August 2017, At: 09:18
 Publisher: Taylor & Francis
Journal: International Journal of Neuroscience
DOI: https://doi.org/10.1080/00207454.2017.1367682

Title: Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation on

Reducing Hemiplegic Shoulder Pain in Patients with Chronic Stoke: A Randomized

Controlled Trial
Downloaded by [Australian Catholic University] at 09:18 15 August 2017

Running title: rTMS in Hemiplegic Shoulder Pain

Author 1: Gyu-sik Choi, MD

1) Professor, Department of Physical Medicine and Rehabilitation, College of Medicine,

Yeungnam University

Author 2 (Corresponding author): Min Cheol Chang, MD

1) Professor, Department of Physical Medicine and Rehabilitation, College of Medicine,

Yeungnam University

2) Mailing Address: Department of Physical Medicine and Rehabilitation, College of

Medicine, Yeungnam University 317-1, Daemyungdong, Namku, Daegu, 705-717, Republic

of Korea

Tel: +82-53-620-4682, e-mail: wheel633@ynu.ac.kr

 Abstract

Objective: To examine whether high-frequency (10 Hz) repetitive transcranial magnetic

stimulation (rTMS), applied over the primary motor cortex of the affected hemisphere, could

be used to manage hemiplegic shoulder pain (HSP).

Methods: Twenty-four chronic stroke patients with chronic HSP, randomly assigned into the

rTMS group (10 sessions of high-frequency stimulation) or the sham group (sham

stimulation), was performed. The Numeric Rating Scale (NRS) was used to evaluate the
Downloaded by [Australian Catholic University] at 09:18 15 August 2017

intensity of pain at pre-treatment, and at one day, and one, two, and four weeks after

treatment. Changes in upper limb motor function were evaluated using the Motricity Index

(MI-UL) and modified Brunnstrom Classification (MBC).

Results: When compared to pretreatment, the rTMS group showed a significant decrease in

the NRS score at one day, and one, two, and four weeks after finishing rTMS sessions, with

no significant change in the sham group. The NRS score after the rTMS sessions reduced by

30.1% at 1 day, 29.3% at 1 week, 28.0% at 2 weeks, and 25.3% at 4 weeks. Passive shoulder

range of motion, MI-UL, and MBC, however, did not significantly change in either group.

Conclusions: High-frequency rTMS could be used as a safe, beneficial therapeutic tool to

manage HSP. We think it can be used as an adjuvant therapeutic modality to enhance the

therapeutic outcome of HSP.

Key words: hemiplegic shoulder pain; stroke; Repetitive transcranial magnetic stimulation

2
 Introduction

After stroke, many patients suffer from several types of pain [1, 2], of which

hemiplegic shoulder pain (HSP) is one of the most frequently occurring conditions [3, 4]. At

4 months after stroke, HSP is known to occur in 87% of patients [5]. Although the majority

of HSP cases are resolved by 6 months, about 20% of patients experience persistent and

debilitating pain in their shoulders [5]. Clinicians use various therapeutic methods, such as

passive range of motion (ROM) exercises, electrical stimulation, analgesic drugs,

Downloaded by [Australian Catholic University] at 09:18 15 August 2017

corticosteroid injection, and botulinum toxin-A injection, to manage HSP [6]. However, even

after the application of these therapeutic tools, many patients with HSP continue to complain

of uncontrolled pain.

Repetitive transcranial magnetic stimulation (rTMS) is a safe, noninvasive, and

effective therapeutic intervention that uses an electromagnetic coil applied to the scalp to

produce a magnetic field. This induces changes in cortical excitability at the stimulation site

and transsynaptically at distant areas [7, 8]. High frequency (≥ 5 Hz) stimulation increases

cortical excitability, whereas low frequency stimulation (1 Hz) decreases it [9, 10]. The

application of high-frequency unilateral rTMS to the motor cortex in patients with chronic

pain has long-term analgesic effects [11-19]. Several previous studies showed its

effectiveness in managing various chronic pain conditions, including neuropathic pain,

fibromyalgia, myofascial pain syndrome, complex regional pain syndrome, and back pain

[11-19]. However, little is known about the effect of rTMS on controlling HSP.

In the current study, we investigated the effects of high-frequency (10 Hz) rTMS

applied over the affected primary motor cortex (M1) for the management of HSP.

3
 Materials and methods

Subjects

We prospectively recruited 24 consecutive stroke patients (13 men, 11 women; 59.0 ±

8.0 years; range, 42–69 years; 14 cerebral infarcts, 10 intracerebral hemorrhages; 12.2 ±

3.5 months from onset) who were admitted to the Department of Physical Medicine and

Rehabilitation at a hospital for undergoing a comprehensive rehabilitation management

Downloaded by [Australian Catholic University] at 09:18 15 August 2017

program. The inclusion criteria was as follows: (1) a history of stroke, (2) ≥ 6 months after

stroke onset, (3) aged between 21–70 years, (4) hemiplegia after stroke, (5) significant

shoulder pain with a minimal score of 4 on the Numeric Rating Scale (NRS, with 0 indicating

no pain and 10 indicating the most severe pain) lasting for at least 3 months, (6) no change in

the pain score on the NRS over 4 weeks despite pain medication (meloxicam and/or

acetaminophen/tramadol hydrochloride), (7) limited passive range of motion (ROM) of a

capsular pattern on physical examination, (8) no history of shoulder corticosteroid injections,

(9) the absence of severe cognitive dysfunction or aphasia, and (10) the absence of

contraindications for TMS such as a history of epileptic seizure, the presence of metal in the

skull, or pacemaker placement. We excluded patients who have central post-stroke pain or

complex regional pain syndrome type I. All patients gave written informed consent. This

study was conducted in compliance with The Code of Ethics of the World Medical

Association (Declaration of Helsinki) for experiments involving humans. Our study protocol

was approved by the institutional review board of our university hospital.

Study design

4
 This study was designed and performed as a prospective, randomized, controlled

clinical trial. All patients were randomly assigned to two groups, the rTMS group and sham

group (n = 12 patients per group), and randomization was performed using a random table.

Each patient underwent 10 consecutive sessions (Monday-Friday, 5 times per week for 2

weeks). The rTMS stimulating location was above the abductor pollicis brevis muscle area of

the precentral gyrus in the affected hemisphere. To confirm the exact location of this area, the

optimal scalp site for the affected cortex was determined using TMS. TMS was performed
Downloaded by [Australian Catholic University] at 09:18 15 August 2017

using a Magstim Super Rapid Magnetic Stimulator (The Magstim Company, Wales, UK),

with a 70 mm, air-cooled coil in the shape of a figure of eight. A cloth marked with 1-cm

spacing and Cz-referenced to the intersection of the midsagittal and interaural lines was

placed on the scalp. Subjects were seated in a comfortable chair with foam earplugs during

TMS.

The motor threshold (MT) was defined as the minimum stimulus required to elicit a

motor evoked potential (MEP) with a peak-to-peak amplitude >50 μV in three out of five

consecutive trials in the APB of the affected side. If the MT was <80%, the stimulation

intensity was set to MT plus 20%, but if the MT was >80% then it was set to 100% of the

stimulator output. MEPs were obtained from the APB muscle of the affected side. Each site

was stimulated 5 times at 1-cm intervals, with a minimum of 10 s between stimulations. We

determined the optimal scalp site for rTMS stimulation, where the stimuli evoked the motor

potentials with maximal peak-to-peak amplitude. In patients who were unresponsive to TMS

stimulation, the exact site of stimulation was defined as the location homologous to the

contralesional motor cortex.

5
 For the patients in the rTMS group, rTMS was administered over the optimal scalp

site at 10 Hz, with an intensity of 90% of the MT and duration of 5 seconds, for a total of 20

trains separated by 55-second intertrain pauses (a total of 1,000 pulses). The coil was placed

tangentially to the scalp at an approximate angle of 45° backward and laterally. The sham

stimulation was administered using the same protocol, except that the angle of the coil was at

a 90º, perpendicular to the skull rather than tangential to it. Thus, the magnetic field could not

penetrate the brain, although the subjects could hear the sound that was produced. The
Downloaded by [Australian Catholic University] at 09:18 15 August 2017

experimenters who applied the rTMS or sham stimulations were different from the

experimenters who performed the clinical evaluation (severity of shoulder pain, passive

shoulder ROM, and motor function). The experimenters who performed the clinical

evaluation were blinded to the group assignment. All patients received movement therapy

(Monday-Friday: 2.5 h/day; Saturday: 1 h/day) for physical conditioning and gait training in

sections of the physical and occupational therapy: motor strengthening of legs and trunk,

exercise for trunk stability and control, and static and dynamic balance training in sitting and

standing positions. .

Clinical evaluation

The assessment of therapeutic effects was performed prior to the start of the study,

and at one day, and one, two, and four weeks after the rTMS sessions. One investigator

assessed clinical outcome at pretreatment and follow-up periods. The investigator was

blinded to the grouping of the patients and did not participate in rTMS stimulation. The

intensity of the pain in the hemiplegic shoulder was rated by the patients during the day using

the NRS, with values between 0 and 10, set as “no pain” and “the most intense pain

6
 imaginable,” respectively. Further, we evaluated the passive shoulder joint ROM. Shoulder

flexion, abduction, and internal and external rotations measurements were also carried out

using a goniometer in supine position. The degrees of shoulder flexion and abduction were

measured with the elbow in extension, and the ROM of internal and external rotations was

evaluated with the elbow at 90° flexion and the arm at 90° abduction, respectively. In order to

measure the exact ROM, the joint should be positioned and the proximal segment stabilized,

thereby isolating the articular movement being evaluated. The examiner moved each
Downloaded by [Australian Catholic University] at 09:18 15 August 2017

subject’s arm until it was limited mechanically or by pain, to measure the passive ROM. To

evaluate motor function, Motricity Index of upper limb (MI-UL) and modified Brunnstrom

Classification (MBC) assessments were used [20].

The change of NRS scores was evaluated by assessing the difference between the

NRS score at pretreatment, and at each evaluation time point after treatment. The calculation

used is as follows: change in NRS [%] = [pretreatment score - score after

treatment]/pretreatment score × 100.

Statistical analysis

Data were analyzed using the Statistical Package for Social Science (SPSS, v. 22.0,

IBM Corporation, Armonk, NY). Summary of the characteristics variables were performed

using descriptive analysis; the values of mean ± standard deviation were presented for

quantitative variables. Demographic data and successful pain relief rate were compared

between the two groups using a Mann-Whitney U test and chi-square test. The clinical

changes in each rTMS and sham group were evaluated using repeated measure one-factor

analysis. Repeated measure two-factor analysis was used to compare changes between groups

7
 over time. Multiple comparisons were obtained following a contrast under Bonferroni

correction. The level of statistical significance was set at p < 0.05.

Results

All patients completed their rTMS sessions. No adverse side effects were reported

during the course of the experiment with the use of rTMS. There were no significant

intergroup differences for the demographic data (p > 0.05) (Table 1).
Downloaded by [Australian Catholic University] at 09:18 15 August 2017

In the rTMS group, the mean NRS decreased after treatment. The pretreatment NRS

was 6.3±1.3. At one day, the mean NRS was 4.3±1.5, at one week, 4.4±1.6, at two weeks,

4.5±1.6, and at four weeks, 4.7±1.7 (Fig. 1). In the sham group, the mean NRS changed from

5.8±1.5 pretreatment, to 6.0±1.5 at one day, 5.9±1.3 at one week, 6.1±1.4 at two weeks, and

5.8±1.4 at four weeks.

The NRS score of the rTMS group significantly differed over time, but that of the

sham group was not significantly changed (rTMS group, p = 0.000; sham group, p = 0.344)

(Fig. 1). In the rTMS group, the NRS scores at one day, and one, two, and four weeks

significantly decreased when compared to pretreatment scores (rTMS group: 1 day, p =

0.000; 1 week, p = 0.001; 2 weeks, p = 0.001; 4 weeks, p = 0.002; sham group: 1 day, p =

0.339; 1 week, p = 0.586; 2 weeks, p = 0.082; 4 weeks, p = 1.000) (Fig. 1). The reduction rate

in the NRS score was evaluated by assessing the difference in the NRS score at pretreatment

and at each evaluation time point after treatment. The rate of reduction of the NRS score after

the rTMS sessions were 30.1% at 1 day, 29.3% at 1 week, 28.0% at 2 weeks, and 25.3% at 4

weeks. However, passive shoulder ROM, MI-UL, and MBC after each of the 10 stimulation

sessions were not significantly different, compared to pretreatment (p > 0.05) (Fig. 2).
8
 In the comparison between groups, the change in the NRS score over time were

significantly different (p = 0.000) (Fig. 1). The NRS score, at one day, and one, two, and four

weeks after rTMS or sham stimulation, was significantly lower in the rTMS group than in the

sham group (1 day, p = 0.000; 1 week, p = 0.000; 2 weeks, p = 0.000; 4 weeks, p = 0.001)

(Fig. 1). However, changes in passive shoulder ROM, MI-UL, and MBC over time were not

significantly different between the groups (p > 0.05) (Fig. 2).

Downloaded by [Australian Catholic University] at 09:18 15 August 2017

Discussion

In the current study, we evaluated the effect of high frequency (10 Hz) rTMS on M1

on the affected hemisphere for the management of HSP in chronic stroke patients. Our results

showed that the severity of pain, measured with the NRS, significantly decreased after high-

frequency rTMS on M1 in the affected hemisphere. This reduction persisted for the four-

week duration of the study. There was approximately a 25–30% reduction rate in pain after

rTMS. In contrast, the NRS score remained unchanged after the sham stimulation. Thus,

rTMS can be helpful to reduce HSP after stroke.

Although the mechanism of pain reduction after rTMS is still unknown, a few

possible mechanisms were postulated. The effects of rTMS on M1 are not limited to the

motor system. Previous fMRI studies demonstrated that rTMS on M1 induces changes in the

activity of cortical and subcortical structures related to pain processing and modulation, such

as the medial thalamus, anterior cingulate, orbitofrontal cortices, and periaqueductal grey

matter [21, 22]. These changes would lead to a reduction of various types of chronic pain. In

relation to this result, in an animal study, the antinociceptive effects of cortical stimulation

were reportedly associated with changes in neuronal activities in the periaqueductal gray

9
 [23]. Also, de Andrade et al.[12] found that the application of rTMS on M1 influences the

endogenous opioid system, which can subsequently reduce the severity of pain.

Currently, corticosteroid injections to site such as the intraarticular and subacromial

bursa are widely used for the management of HSP [24, 25]. Although several previous studies

have demonstrated its positive effects for controlling HSP [24, 25], its efficacy had led to

some controversy about its use [26]. Also, the potential for adverse effects of steroids, which

include suppression of the pituitary-adrenal axis, hyperadrenocorticism, avascular necrosis,

Downloaded by [Australian Catholic University] at 09:18 15 August 2017

osteoporosis, steroid myopathy, weight gain, and hyperglycemia, must be considered [27,

28]. Also, after taking oral analgesics, various adverse effects, such as nausea, vomiting,

constipation, drowsiness, gastritis, can be manifested [29]. Thus, we suggest that rTMS could

be a helpful therapeutic tool to treat HSP, especially for patients who have significant side

effects or contraindications to corticosteroid injection or oral analgesics. Further, we think

that it also can successfully be used as an adjuvant therapeutic modality to control HSP after

stroke.

We applied high-frequency rTMS on M1 of the affected hemisphere because the

activation of motor areas of the unaffected hemisphere could have exhibited abnormally high

interhemispheric inhibition to the motor cortex of the affected hemisphere, accordingly

weakening motor function and inhibiting the recovery of the affected limb [30]. Several

previous studies reported that rTMS induces improvements of motor function in stroke

patients [30-33]. However, the current study did not show any significant improvements in

the patients’ motor function. It is possible that the MI and MBC might not reflect detailed

changes in motor function, and thus, further evaluation with using better measures is

required. However, considering the fact that 95% of stroke patients only complete their

10
 functional recovery within 12.5 weeks from onset [34, 35], our finding that motor function

was not significantly improved within follow-up period is acceptable. We were also unable to

demonstrate a significant change in passive shoulder ROM. Limited ROM of the shoulder is

known to be due to a combination of synovial inflammation and capsular fibrosis [36]. Based

on our results, we think that rTMS has no anti-inflammatory or anti-fibrotic effects. Thus, the

treatment must be combined with ROM exercise or botulinum toxin-A injection to increase

shoulder ROM [37, 38].

Downloaded by [Australian Catholic University] at 09:18 15 August 2017

To date, a dozen of studies have reported the positive effects of rTMS on the motor

cortex (M1 or dorsolateral prefrontal cortex) for controlling central neuropathic pain after

stroke [39-49], with the effects sustained for approximately 2–4 weeks [39, 41, 43, 48, 49].

However, apart from these studies with a focus on central neuropathic pain, there are no

studies on other types of pain. Therefore, this is the first study to evaluate the effectiveness of

high-frequency rTMS in patients with chronic HSP.

In conclusion, although the rate of pain relief after rTMS was only 25-30%, we found

that chronic HSP refractory to oral analgesics was significantly reduced at 1 day, and 1, 2,

and 4 weeks after high-frequency rTMS over M1 of affected hemisphere. Thus, rTMS

would be useful and safe therapeutic tool to control HSP, especially for patients who have

contraindications to other therapeutic methods, such as corticosteroid injection and oral

analgesics. In addition, a combination of rTMS and other therapies would be helpful for

better outcomes. However, some limitations of this study should be considered. First, we did

not evaluate serial changes in the clinical data during the 2-week the treatment session and

the 4-week period after treatment. Second, we did not investigate the long-term effects of

therapy beyond 4 weeks. Third, the number of recruited patients was small. Finally, the sham

11
 stimulation used in our study mimicked only the sound of the coil discharge, and could not

mimic cutaneous sensation or twitches of scalp muscles during rTMS stimulation. Therefore,

further studies addressing these limitations are necessary to confirm the findings in the

current study.

Disclosure statement

The authors report no conflicts of interest.

Downloaded by [Australian Catholic University] at 09:18 15 August 2017

References

1. Choi-Kwon S, Choi SH, Suh M, et al. Musculoskeletal and central pain at 1 year post-

stroke: associated factors and impact on quality of life. Acta Neurol Scand 2016 [Epub ahead

of print]

2. Snels IA, Beckerman H, Lankhorst GJ, et al. Treatment of hemiplegic shoulder pain in The

Netherlands: Results of a national survey. Clin Rehabil 2000;14:20–7.

3. Lindgren I, Jonsson AC, Norrving B, et al. Shoulder pain after stroke: a prospective

population-based study. Stroke 2007;38:343–8.

4. Ratnasabapathy Y, Broad J, Baskett J, et al. Shoulder pain in people with a stroke: a

population-based study. Clin Rehabil 2003;17:304–11.

5. Gamble GE, Barberan E, Laasch HU, et al. Poststroke shoulder pain: a prospective study

of the association and risk factors in 152 patients from a consecutive cohort of 205 patients

presenting with stroke. Eur J Pain 2002;6:467-74.

12
 6. Viana R, Pereira S, Mehta S, et al. Evidence for therapeutic interventions for hemiplegic

shoulder pain during the chronic stage of stroke: a review. Top Stroke Rehabil 2012;19:514-

22.

7. Gu SY, Chang MC. The effects of 10-Hz Repetitive transcranial magnetic stimulation on

depression in chronic stroke patients. Brain Stimulation 2017;10:270-4.

8. Ziemann U, Corwell B, Cohen LG. Modulation of plasticity in human motor cortex after

forearm ischemic nerve block. J Neurosci 1998;18:1115-23.

Downloaded by [Australian Catholic University] at 09:18 15 August 2017

9. Mansur CG, Fregni F, Boggio PS, et al. A sham stimulation-controlled trial of rTMS of the

unaffected hemisphere in stroke patients. Neurology 2005;64:1802-4.

10. Peinemann A, Reimer B, Löer C, et al. Long-lasting increase in corticospinal excitability

after 1800 pulses of subthreshold 5 Hz repetitive TMS to the primary motor cortex. Clin

Neurophysiol 2004;115:1519-26.

11. Ambriz-Tututi M, Alvarado-Reynoso B, Drucker-Colín R. Analgesic effect of repetitive

transcranial magnetic stimulation (rTMS) in patients with chronic low back pain.

Bioelectromagnetics. 2016 [Epub ahead of print].

12. de Andrade DC, Mhalla A, Adam F, et al. Neuropharmacological basis of rTMS-induced

analgesia: the role of endogenous opioids. Pain 2011;152:320-6.

13. Lee SJ, Kim DY, Chun MH, et al. The effect of repetitive transcranial magnetic

stimulation on fibromyalgia: a randomized sham-controlled trial with 1-mo follow-up. Am J

Phys Med Rehabil 2012;91:1077-85

13
 14. Leung A, Fallah A, Shukla S, Lin L, Tsia A, Song D, et al. rTMS in Alleviating Mild TBI

Related Headaches--A Case Series. Pain Physician 2016; 19(2): E347-54.

15. Medeiros LF, Caumo W, Dussán-Sarria J, et al. Effect of Deep Intramuscular Stimulation

and Transcranial Magnetic Stimulation on Neurophysiological Biomarkers in Chronic

Myofascial Pain Syndrome. Pain Med 2016;17:122-35.

16. Ma SM, Ni JX, Li XY, et al. High-Frequency Repetitive Transcranial Magnetic

Stimulation Reduces Pain in Postherpetic Neuralgia. Pain Med 2015;16:2162-70.

Downloaded by [Australian Catholic University] at 09:18 15 August 2017

17. Pérocheau D, Laroche F, Perrot S. Relieving pain in rheumatology patients: repetitive

transcranial magnetic stimulation (rTMS), a developing approach. Joint Bone Spine

2014;81:22-6.

18. Sacco P, Prior M, Poole H, et al. Repetitive transcranial magnetic stimulation over

primary motor vs non-motor cortical targets; effects on experimental hyperalgesia in healthy

subjects. BMC Neurol 2014;14:166.

19. Tzabazis A, Aparici CM, Rowbotham MC, et al. Shaped magnetic field pulses by multi-

coil repetitive transcranial magnetic stimulation (rTMS) differentially modulate anterior

cingulate cortex responses and pain in volunteers and fibromyalgia patients. Mol Pain

2013;9:33.

20. Jang SH, Choi BY, Chang CH, et al. Prediction of motor outcome based on diffusion

tensor tractography findings in thalamic hemorrhage.. Int J Neurosci 2013;123:233-9.

21. Almeida TF, Roizenblatt S, Tufik S. Afferent pain pathways: a neuroanatomicalreview.

Brain Res 2004;1000:40–56.

14
 22. Mylius V, Borckardt JJ, Lefaucheur JP. Non-invasive cortical modulation of experimental

pain. Pain 2012;153:1350–63.

23. Pagano RL, Fonoff ET, Dale CS, et al. Motor cortex stimulation inhibits thalamic sensory

neurons and enhances activity of PAG neurons: possible pathways for antinociception. Pain

2012;153:2359-69.

24. Chang MC. The effects of ultrasound-guided corticosteroid injection for the treatment of

hemiplegic shoulder pain on depression and anxiety in patients with chronic stroke. Int J
Downloaded by [Australian Catholic University] at 09:18 15 August 2017

Neurosci 2017 [Epub ahead of print].

25. Dekker JHM, Wagener RC, Lankhorst GJ, et al. The painful hemiplegic shoulder: Effects

of intra-articular triamcinolone acetonide. Am J Phys Med Rehabil 1997;76:43–8.

26. Bowen A, James M, Young G. Royal College of Physicians National Stroke Guideline

5th edition. 2016; p81.

27. Manchikanti L. Role of neuraxial steroids in interventional pain management. Pain

Physician 2002;5:182-99.

28. Manchikanti L, Boswell MV, Singh V, Benyamin RM, Fellows B, Abdi S, et al; ASIPP-

IPM. Comprehensive evidence-based guidelines for interventional techniques in the

management of chronic spinal pain. Pain Physician 2009;12:699-802.

29. Rogoveanu OC, Streba CT, Vere CC, Petrescu L, Trăistaru R. Superior digestive tract

side effects after prolonged treatment with NSAIDs in patients with osteoarthritis. J Med Life

2015;8:458-61

15
 30. Lin YN, Hu CJ, Chi JY, et al. Effects of repetitive transcranial magnetic stimulation of

the unaffected hemisphere leg motor area in patients with subacute stroke and substantial leg

impairment: A pilot study. J Rehabil Med 2015;47:305-10.

31. Kakuda W, Abo M, Nakayama Y, et al. High-frequency rTMS using a double cone coil

for gait disturbance. High-frequency rTMS using a double cone coil for gait disturbance.

Acta Neurol Scand 2013;128:100–6.

32. Kakuda W, Abo M, Watanabe S, et al. High-frequency rTMS applied over bilateral leg
Downloaded by [Australian Catholic University] at 09:18 15 August 2017

motor areas combined with mobility training for gait disturbance after stroke: A preliminary

study. Brain Inj 2013;27:1080–6.

33. Naghdi S, Nakhostin Ansari N, et al. A pilot study on the effects of low frequency

repetitive transcranial magnetic stimulation on lower extremity spasticity and motor neuron

excitability in patients after stroke. J Bodyw Mov Ther 2015;19:616-23.

34. Dobkin BH. Rehabilitation after stroke. N Engl J Med 2005;352:1677–84.

35. Jørgensen HS, Nakayama H, Raaschou HO, et al. Stroke: neurologic and functional

recovery the Copenhagen Stroke Study. Phys Med Rehab Clin N Am 1999;10:887–906.

36. Hsu JE, Anakwenze OA, Warrender WJ, et al. Current review of adhesive capsulitis. J

Shoulder Elbow Surg 2011;20:502-14.

37. Lim JY, Koh JH, Paik NJ. Intramuscular botulinum toxin-A reduces hemiplegic shoulder

pain: a randomized, double-blind, comparative study versus intraarticular triamcinolone

acetonide. Stroke 2008;39:126-31.

16
 38. Lynch D, Ferraro M, Krol J, et al. Continuous passive motion improves shoulder joint

integrity following stroke. Clin Rehabil 2005;19:594-9.

39. de Oliveira RA, de Andrade DC, Mendonça M, et al. Repetitive transcranial magnetic

stimulation of the left premotor/dorsolateral prefrontal cortex does not have analgesic effect

on central poststroke pain. J Pain 2014;15:1271-81.

40. Goto T, Saitoh Y, Hashimoto N, et al. Diffusion tensor fiber tracking in patients with

central post-stroke pain; correlation with efficacy of repetitive transcranial magnetic

Downloaded by [Australian Catholic University] at 09:18 15 August 2017

stimulation. Pain 2008;140:509-18.

41. Hasan M, Whiteley J, Bresnahan R, et al. Somatosensory change and pain relief induced

by repetitive transcranial magnetic stimulation in patients with central poststroke pain.

Neuromodulation 2014;17:731-6;discussion 736.

42. Hosomi K, Kishima H, Oshino S, et al. Cortical excitability changes after high-frequency

repetitive transcranial magnetic stimulation for central poststroke pain. Pain 2013;154:1352-

7.

43. Khedr EM, Kotb H, Kamel NF, et al. Longlasting antalgic effects of daily sessions of

repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. J

Neurol Neurosurg Psychiatry 2005;76:833-8.

44. Kobayashi M, Fujimaki T, Mihara B, et al. Repetitive transcranial magnetic stimulation

once a week induces sustainable long-term relief of central poststroke pain. Neuromodulation

2015;18:249-54.

17
 45. Le Déan Y, Brissebrat B, Castel-Lacanal E, et al. Management of neuropathic central

pain by non-invasive brain stimulation and mirror therapy. Ann Phys Rehabil Med

2016;59S:e145.

46. Lefaucheur JP, Drouot X, Menard-Lefaucheur I, et al. Neurogenic pain relief by repetitive

transcranial magnetic cortical stimulation depends on the origin and the site of pain. J Neurol

Neurosurg Psychiatry 2004;75:612-6.

47. Matsumura Y, Hirayama T, Yamamoto T. Comparison between pharmacologic

Downloaded by [Australian Catholic University] at 09:18 15 August 2017

evaluation and repetitive transcranial magnetic stimulation-induced analgesia in poststroke

pain patients. Neuromodulation 2013;16:349-54;discussion 354

48. Ohn SH, Chang WH, Park CH, et al. Neural correlates of the antinociceptive effects of

repetitive transcranial magnetic stimulation on central pain after stroke. Neurorehabil Neural

Repair 2012; 26:344-52.

49. Saitoh Y, Maruo T, Yokoe M, et al. Electrical or repetitive transcranial magnetic

stimulation of primary motor cortex for intractable neuropathic pain. Conf Proc IEEE Eng

Med Biol Soc 2013;2013:6163-6.

18
Downloaded by [Australian Catholic University] at 09:18 15 August 2017

Fig. 1. Numeric rating scale (NRS) changes. When compared to pretreatment, the repetitive

transcranial stimulation (rTMS) group showed a significant decrease in the NRS score at one

day, and at one, two, and four weeks after finishing the rTMS sessions. However, there was

no significant change in the sham group. In the intergroup comparison, the NRS score was

significantly lower in the rTMS group than in the sham group.

19
Downloaded by [Australian Catholic University] at 09:18 15 August 2017

Fig. 2. Changes in passive shoulder joint range of motion (ROM) and motor function. The

ROM of the shoulder and upper limb Motricity Index (MI-UL), and modified Brunnstrom

Classification (MBC) were not significantly different compared to pretreatment, in both the

repetitive transcranial stimulation (rTMS) and the sham groups. In the intergroup

comparison, the changes in the ROM of the shoulder, MI-UL, and MBC over time were not

significantly different between groups.

20
 Table 1. Patient demographic and initial clinical data

rTMS group Sham group p value

(n = 12) (n = 12)

Age, years 60.3 ± 7.1 57.8 ± 8.9 0.551

Sex (M:F), n 7:5 6:6 0.682

Months from onset 12.6 ± 3.0 11.8 ± 4.0 0.410

Downloaded by [Australian Catholic University] at 09:18 15 August 2017

Stroke type (infarct:hemorrhage), n 7:5 7:5 1.000

Initial NRS 6.3 ± 1.3 5.8 ± 1.5 0.551

Initial limitation of passive ROM of

shoulder, degree

Flexion 48.3 ± 25.5 43.8 ± 30.7 0.630

Abduction 51.7 ± 28.2 44.2 ± 28.4 0.378

External rotation 25.0 ± 11.7 29.2 ± 16.2 0.713

Internal rotation 19.6 ± 8.6 23.3 ± 11.3 0.551

Initial MBC 3.3 ± 1.4 3.1 ± 1.4 0.671

Initial FAC 2.8 ± 0.7 2.9 ± 0.7 0.799

Initial MI-UL 54.4 ± 16.0 52.0 ± 16.7 0.799

Initial MI-LL 52.4 ± 14.1 50.0 ± 15.8 0.755

MMSE 26.4 ± 3.3 27.3 ± 2.5 0.590

Values represent the mean ± standard deviation.

Abbreviations: NRS, numeric rating scale; ROM, range of motion; MBC, modified

Brunnstrom Classification (scores range from 1–6 and higher scores indicate better hand

21
 function); FAC, Functional Ambulation Category (scores range from 0–5 and higher scores

indicate better walking ability); MI-UL, upper limb Motricity Index; MI-LL, lower limb

Motricity Index; MMSE, mini-mental state examination.

*p < 0.05: intragroup comparison between NRS at post-treatment and that at pretreatment

(repeated measure one-factor analysis)

†
p < 0.05: intergroup comparison in each time point (repeated measure two-factor analysis)
Downloaded by [Australian Catholic University] at 09:18 15 August 2017

22