Title: Non-Pharmacological Treatment for Painful Diabetic Neuropathy: A Systematic Review

Authors’ full names

1. First author : Agung Laksana Hendra Pamungkas (Corresponding Author)

2. Second author : Amin Samiasih

3. Third author : Edy Soesanto

4. Fifth author : Satriya Pranata

Authors' institutional affiliations

1. Author : Agung Laksana Hendra Pamungkas (1st author)

Affiliation : Faculty of Nursing and Health Science, Universitas Muhammadiyah

Semarang, Semarang, Central Java 50273, Indonesia.

Email : hendrambontot@gmail.com

ORCID : 0000-0003-1180-2730

Address : Tegal, Central Java, Indonesia

2. Author : Amin Samiasih (2nd author )

Affiliation : Department of Nursing, Faculty of Nursing and Health Science, Universitas

Muhammadiyah Semarang, Semarang, Central Java 50273, Indonesia

Email : aminsamiasih@unimus.ac.id

ORCID : 0000-0002-2482-961X

Address : Semarang, Indonesia

3. Author : Edy Soesanto (3rd author )

Affiliation : Department of Nursing, Faculty of Nursing and Health Science, Universitas

Muhammadiyah Semarang, Semarang, Central Java 50273, Indonesia

 Email : soesantoedisoes@gmail.com

ORCID : 000-0002-3651-7330

Address : Semarang, Indonesia

4. Author : Satriya Pranata (4th author )

Affiliation : Department of Nursing, Faculty of Nursing and Health Science, Universitas

Muhammadiyah Semarang, Semarang, Central Java 50273, Indonesia

Email : satriya.pranata@unimus.ac.id

ORCID : 0000-0002-2026-8931

Address : Kedungmundu Street, Semarang City, Central Java, Indonesia

Conflict of Interest statement

The authors declared no potential conflicts of interest in respect to the research, authorship, and

publication of this article.

Funding Statement

None
Non-Pharmacological Treatment for Painful Diabetic Neuropathy: A Systematic Review

Abstract

Background: Pharmacological treatment of neuropathic pain has various side effects, while

non-pharmacological therapy has been shown to have minimal risk of side effects.

Objective: To explore more deeply about the types of non-pharmacological therapies that can

be used to treat neuropathic pain in patients with diabetes mellitus.

Methods: Article searches were performed using Science Direct, Pubmed, Google Schoolar

and EBSCO to find articles according to inclusion and exclusion criteria. Articles that meet

the criteria set by the author are then analyzed, determined by the level of evidence,

extracted and then synthesized.

Results: Non-pharmacological therapies that have been shown to be able to reduce

neuropathic pain in diabetic patients are electrical stimulation, Low Intensity Laser Therapy

(LILT), Repetitive Magnetic Stimulation, Acceptance and Commitment Therapy (ACT),

Hydrotherapy, Aromatherapy Massage, Exercises Training, Acupuncture and china Herbal

Medicine. Among these interventions, acupuncture and electrical stimulation were the most

widely used interventions to reduce neuropathic pain in diabetic patients.

Conclusion: Non-pharmacological therapy is able to reduce neuropathic pain in diabetes

mellitus, it is hoped that in the future research using the RCT method with a large number of
 samples can be generalized.

Keywords: pain, non-pharmacology, neuropathy diabetic

A. BACKGROUND

Diabetes is a chronic disease in the form of metabolic disorder characterized by elevated levels of

blood glucose above normal (Hinkle & Cheever, 2018; Kemenkes, 2020). Indonesia ranks fifth

form the number of diabetics in the world at 19,5 million, it is estimated in 2045 this number will

rise to 28,4 million (IDF, 2021).

 The challenge for nurses in response to the rise of diabetics definitely getting bigger because

problems that will arise based on body response will also be complex (Pranata, 2017). One is

related to many kinds of complications. Complications that occur in diabetics are macrovascular

complications and microvascular complications. One of the most common microvascular

complications is diabetic neuropathy (Jaiswal et al., 2017). If diabetic neuropathy isn’t treated

immediately, it may causes a decrease in the patient’s quality of life (Shillo et al., 2019). The

results of the study show that neuropathy pain can affect patients to experience sleep disorders,

symptoms of anxiety and depression, decrease appetite and even decrease in immunity

(Gylfadottir et al., 2020; Suwondo et al., 2017).

Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory system

(Sobhy, 2016). There are two ways to treat diabetic neuropathic pain, that’s pharmacological and

non-pharmacological. Pharmacological pain management has a risk of side effects in

gastrointestinal disorders, kidney disorders, liver disorders, and heart disorders. Meanwhile, non-

pharmacological pain management has minimal side effects (Brunner & Suddarth, 2022).

There’re not many studies that explored about types of non-pharmacological therapies to reduce

neuropathic pain in diabetic patients. So that, systematic review of the types of non-

pharmacological therapies that can reduce neuropathic pain is needed.

B. PURPOSES

The purposes of this systematic review is to delve deeper about the types of non-pharmacological

therapies that can be used to treats neuophatic pain in diabetic patients

C. METHOD

Design
The types of research designs that are included in this systematic review are systematic reviw

meta-analyses, RCTs, quasy experiments, and literature reviews. This type of research design is

deemed to have been able to answer predetermined clinical questions.

Inclusion and exclusion criteria

Type of Study

The types of study that will be reviewed is all types of research that use non-pharmacological

therapies to reduce neuropathic pain in patients with diabetes.

Type of participants/ respondent

Participants who were determined to be reviewed are adults patiebts who experienced diabetic

neropathic pain. All participants who meet these criteria are included as participants in systematic

review.

Type of Intervention

Interventions that were included in the inclusion criteria are all types of non-pharmacological

therapeutic interventions that were carried out to reduce the level of diabetic neuropathic pain.

Type of Measured Outcome

The types of outcome that will be measure is limited to the effects of non-pharmacological

therapies on the level of neuropathic pain in patient with diabetes.

Systematic review search strategy

This systematic review is carried out by searching published research articles, We used keywords

non pharmacological treatment AND complementary OR alternative medicine AND pain

neuropathy AND diabetic for funding the articles. The population in this study are diabetic

neuropathic patients who received non-pharmacological therapy, and the results are reduced

levels of diabetic neuropathic pain. Searches are made by using EBSCO search engine which

include of Medline, CINAHL, Science direct, Google Schoolar, and Pubmed with keywords for

each variable that has been selected. Articles that found from each of those searches, then will be

read carefully to see which articles that met the author’s inclusion criteria to be a literature in this
 systematic review. The search is limited from 2017 – 2022 which can be full text accessed in pdf

format with a systematic review meta analysis design, RCTs, quasy experiment, and literature

review. Every published research articles that performs non-pharmacological therapy and its able

to reduced neuropathic pain in diabetics, will be included in a systematic review.

The method of assesing the quality of study articles that match to the defined criteria, will be

analyzed and determined by the level of the evidence up to do data extraction and synthesis. The

expectation from these many studies is obtaining a conclusion which later become the basis for

nursing practice in hospitals, society, or community.

Extraction data method

Extraction of research data are done by reading a research’s results then taking the essences of the

research. The essence of research that has been taken are the tittle of study, name of the

researcher, the research method, the number of samples by looking at the characteristic sample

and the number of interventions and control groups, the instrument that has been used, and the

final results completed with significance value. All the parts are organized in a table to make

extraction results easier to read.

Medline (n ＝ 16 articles)
CINAHL (n ＝ 15 articles)
Google Schoolar (n ＝ 7.400 articles)
Pubmed full text (n = 12 articles)
Library,information science and technology abstract (n ＝
Search 8 articles)
Scien direct (n ＝892 articles)
 Total number of articles (n =8.343)

Articles excluded for being unsuitable or irrelevant after

filtering (n = 5.492)
1. Duplication (n = 759)
Filter 2. Article not aligned with tailored care (n = 409)
3. Incomplete (n =90)
4. Participants not having diabetes (n = 1443)
5. Unrelated with tailored care education concepts (n = 112)

Qualified Full-text articles included in systematic

review (n = 150 ) Full-text articles were
excluded because they
were not related to
tailored care education
for diabetes (n = 132)
Articles included in the analysis
Included (n = 18)

Figure 1. Flowchart of screening articles on tailored care education for diabetes.

D. RESULTS

To get the research articles it needs, author run a search with keywords. The number of articles

that were obtained and meet the inclusion and exclusion criteria are 18 articles which 9 were

systematic review articles, 6 RCT articles, 2 experimental articles, and 1 literature review.

Research on the management of neuropathic pain may be performed with electrical stimulation

(Adehunoluwa et al., 2019; Bose & Karthikeyan, 2021), acupunture therapy (Dietzel et al., 2021;

Dimitrova et al., 2017; Huang et al., 2019; Nash et al., 2019), massage therapy (Gok Metin et al.,

2017; Ren et al., 2022), herbal therapy (Hutapea & Simbolon, 2022; Shi et al., 2021),

hydrotherapy (Shourabi et al., 2020), ACT psychotherapy (Davoudi et al., 2020), Exercises

Training (Cox et al., 2020; Win et al., 2020). Those articles is then analyzed. The following is the

lists of extracted articles in tabular form : (the extraction table can be seen at the end of this

article.

Table 1. The level of evidence and quality of the articles

No of Level of
Author & years Method Summary
articles evidence
Emmanuel et al.. Sistematic review
1 2 Good
(2019)
Tanmay, K and Mr. M.Karthikeyan Eksperimental study
2 4 Fair
(2021)
Andreas, L et al. Sistematic review
3 2 Good
(2020)
Abdullah, Amir et al. Sistematic review
4 2 Good
(2020)
Barnetti, Andrea et al. Sistematic review
5 2 Good
(2021)
Anju M, et al. Sistematic review
6 2 Good
(2019)
Davaodi, Mohammad reza et al. Randomized clinical
7 1 Good
(2020) trial
Dietzl J, et al. Randomized clinical
8 1 Good
(2021) trial
Wang Li-Qin, et al. Sistematic review
9 2 Good
(2020)
Dimitrova Alexandra, Murhison Charles, Okan Sistematic review
10 Barry and Meta Analisis 2 Good
(2017)
 Nash Jane, Armour Mike & Penkala Sistematic review
11 Stefania 2 Good
(2019)
Longsheng Ren, et al. Sistematic review
12 2 Good
(2022)
Yong Shi, et al. Randomized clinical
13 1 Good
(2021) trial
Pouria Shourabi et al. Semi-experimental
14 4 Good
(2020) study
Zehra Gok Metin, et al. Randomized clinical
15 1 Good
(2017) trial
lbert Manggading Hutapea & Boyke Literatur review
16 Marthin Simbolon 5 Fair
(2022)
Mi Mi Thet Mon Win, et al. Randomized clinical
17 1 Good
(2019) trial
Emily R. Cox et al.. Randomized clinical
18 1 Good
(2020) trial

Table 2. Extraction table of the included studies

Title Significant to the

No Objectives Methods Results
Author (years) topic under review
1. Effectiveness of This study is a Sistematic The outcome of Transcutaneous
electrical systematic review review this study was that electrical nerve
stimulation and of the evidence to TENS and other stimulation (TENS),
low intensity enable the forms of electrical pulsed-dose
laser determination of stimulation electrical
therapy the effectiveness reviewed in this stimulation,
on of electrical study may be frequency modulated
diabetic stimulation and effective and safe electromagnetic
neuropathy:A low-intensity laser non- neural stimulation,
systematic therapy (LILT) pharmacological have been reported
review treatment effective in
Emmanuel et al.. modalities in managing diabetic
(2019) relieving the neuropathy
symptoms
associated with
diabetic
neuropathy, The
effectiveness of
LILT couldn’t be
determined due to
the different
parameters used to
evaluate patients’
outcome and
limited number of
studies
2 Effectiveness of The aim of the Eksperimental Group B is more Transcutaneous
Transcutaneous study is to find study Sampel: 45 significant than Electrical Nerve
Electrical Nerve whether the responden Group A and Stimulation
Stimulation In Transcutaneous Group A (15 Group C.In this (TENS) reduce pain
Chronic Painful Electrical Nerve subjects): study, we observed & discomfort of
Diabetic Stimulation receives only that the Chronic Painful
Neuropathy (TENS) is Medication for Transcutaneous Diabetic Neuropathy.
Tanmay, K and effective for Painful Diabetic Electri cal Nerve
Mr. Chronic Neuropathy Stimulation
M.Karthikeyan Painful Diabetic (PDN), Group B (TENS) reduce
(2021) Neuropathy (PDN) (15 subjects) : pain & discomfort
in case of Type 2 receives of Chronic Painful
Diabetes Mellitus. Medication and Diabetic
Transcutaneous Neuropathy.
Electrical Nerve
Stimulation
(TENS) and
Group C (15
subjects):receives
Medication and
SHAM (TENS)
(with Frequency
2- 70 HZ.Wave
from :Biphasic,
Pulse width: 4
ms,Intensity:> 35
mA, and
Treatment time :
40 min)
3 Non- The aim of this Systematic Adjuvant repetitive Repetitive
Pharmacological systematic review review transcranial transcranial
Management of was to evaluate the magnetic magnetic stimulation
Painful current evidence, stimulation of the of the motor cortex is
Peripheral derived motor cortex is effective in reducing
Neuropathies: A from randomized effective in the overall pain
Systematic controlled trials reducing the intensity
Review (RCTs) that assess overall pain
Andreas, L et al. non- intensity,
(2020) pharmacological whereas adjuvant
interventions for static magnetic
the treatment of field therapy can
PNP. lead to a significant
decrease in
exerciseinduced
pain. Weaker
evidence (level III
of evidence) exists
for the use of
acupuncture as a
monotherapy and
neurofeedback,
 either as an
add-on or a
monotherapy
approach, for
treatment of painful
chemotherapy-
induced peripheral
neuropathy
4 Repetitive identify the Systematic Repetitive Repetitive magnetic
Magnetic available literature review magnetic stimulation (RMS)
Stimulation for regarding the use Sampel: stimulation (RMS) has a definite
the Management of RMS in the identified 12 has a definite immediate effect in
of Peripheral treatment of papers eligible to immediate effect in pain relief
Neuropathic Pain: peripheral be included in pain relief which,
A Systematic neuropathic pain. this review. in the majority of
Review studies, is
Abdullah, Amir et maintained for a
al. few weeks.
(2020)
5 Neuropathic Pain to analyze the systematic review Six guidelines were This analysis
and most indicated analyzed, from highlights the
Rehabilitation: A therapeutic which emerges that importance
Systematic strategies, a multidisciplinary of rehabilitation but
Review of providing approach, also the lack of
International rehabilitative comprehensive of evidence on various
Guidelines recommendations pharmacologic rehabilitative
Barnetti, Andrea in the management and practices.
et al. of neuropathic nonpharmacologic
(2021) pain interventions,
should drive
neuropathic pain
management.
6 Low level laser focused on finding systematic review 6 studies were The evidence
therapy for the evidence on the included in the obtained shows
patients with effectiveness of study. The outcome LLLT has a positive
painful diabetic LLLT on measure that were effect in controlling
peripheral treatment of considered were diabetic neuropathic
neuropathy - A painful diabetic the difference in pain.
systematic review neuropathy. pain score and
Anju M, et al. nerve conduction
(2019) velocity test and
quality of life
questionnaire.
7 Effectiveness of To assess the Randomized Results showed Conclusion ACT, as
Acceptance and effectiveness of clinical trial that in the a complementary
Commitment Acceptance and 50 participants intervention group, treatment, can
Therapy (ACT) Commitment were separated the treatment led to improve the
on depression and Therapy on Into intervention improved psychiatric
sleep quality in depression and and control depressive symptoms and
painful diabetic Sleep disturbance groups randomly. symptoms (F = 81, problems in people
neuropathy: in patients with Based on the P <0.05). with neuropathic
 a randomized painful diabetic diagnosis of Besides, for sleep pain. Therefore, it is
clinical trial neuropathy. neurologists, all quality, treatment necessary to include
Davaodi, participants in all subscales, psychotherapy
Mohammad reza received tandard except for the services along with
et al. medications Hypnotic medicine medical treatment in
(2020) to regulate subscale, outpatient and
neuropathic pain. significantly hospitalization units.
The intervention improved the
group received intervention
ACT for eight group’s situations.
sessions. The It was also
results were observed that the
evaluated in the overall quality of
pre-test, post-test, sleep in the ACT
and follow-up. group showed a
The tools used more significant
were the improvement (P <
pittsburgh sleep 0.05). All the above
quality index results remained
(PSQI) and the same until the
Beck’s epression end of the follow-
inventory. up period (P 0.05)
8 Acupuncture in To investigate This study is a The results of this Acupuncture can be
diabetic peripheral whether two-armed, trial will be considered effective
neuropathy— acupuncture is randomized, available in 2021 for the treatment of
protocol for the effective for the controlled, and will help DPN with regard to
randomized, treatment of DPN parallel group, clarify whether the subdimensions of
multicenter symptoms. open-label, acupuncture can be the neuropathic
ACUDPN trial confirmatory, considered
Dietzl J, et al. multicenter trial effective for the
(2021) (8-week treatment of DPN
intervention with regard to the
period plus 16 subdimensions of
weeks of follow- the neuropathic
up) clinical picture
9 Effectiveness of Thus, this Systematic This study will Therefore, this study
warm needling systematic review Review summarize the aims to assess the
acupuncture will evidence for the effect and
(WNA) for comprehensively effectiveness and safety of WNA for
pain relief in and systematically safety of WNA for pain in DPN
patients with investigate the the management of
diabetic peripheral effectiveness and pain in patients
neuropathy safety of WNA for with
Wang Li-Qin, et pain relief in DPN. DPN
al.
(2020)
10 Acupuncture for to assess the Systematic Fifteen studies Acupuncture is
the Treatment of efficacy of Review and were included: 13 beneficial in some
Peripheral acupuncture in the Meta-Analysis original RCTs, a peripheral
Neuropathy: treatment of long-term follow- neuropathies, but
A Systematic neuropathy of up, and a re- more rigorously
 Review and Meta- various etiologies. analysis of a prior designed
Analysis RCT. The majority studies using sham-
Dimitrova of RCTs showed acupuncture control
Alexandra, benefit for are needed to
Murhison Charles, acupuncture over characterize its effect
Okan Barry control in the and optimal use
(2017) treatment of better.
diabetic neuropathy
11 Acupunture for To examine Systematic Five electronic The application of
the treatment of evidence for review database were acupuncture vries
lower limb acupuncture search up for greatly and the
diabetic intervention in the studies that include quality of include
peripheral management of participants with studi was generally
neuropathy: a diabetes-related symptoms of DPN low.
systematic peripheral used acupuncture
Review neuropathy (DPN) intervention
Nash Jane, symptoms reported before and
Armour Mike & after DPN related
Penkala Stefania outcomes measures
(2019)
12 The efficacy and This study will Systematic RCTs will be used However, massage
safety of explore the review Eight to evaluate the therapy for DPN
massage effectiveness and electronic clinical efficacy of lacks evidence-based
adjuvant safety of databases massage adjuvant support.
therapy in the massage applied in (PubMed, therapy in DPN.
treatment of DPN. Cochrane, Web of This study will
diabetic Science, provide evidence-
peripheral Sinomed, based evidence for
neuropathy Embase, China the safety and
Longsheng Ren, National effectiveness of
et al. Knowledge massage adjuvant
(2022) Infrastructure, therapy in DPN
WanFang Data,
Chongqing VIP
Information).RC
T of djuvant
massage therapy
for DPN was
screened.
13 Efficacy and Sistematic review Randomized This study will Results will provide
safety of will controlled trials provide a high- credible evidence to
acupuncture comprehensively Searched in 9 quality support the clinical
combined and systematically databases before comprehensive selection of
Chinese herbal investigate the September of evaluation of the acupuncture
medicine for effectiveness and 2021 including safety of combined with
diabetic safety of Medline, Web of acupuncture Chinese herbal
peripheral acupuncture Science, PubMed, combined with medicine
Neuropathy combined with Cochrane Chinese herbal and encourage wider
Yong Shi, et al. Chinese herbal Library, Excerpta medicine for acceptance of
(2021) medicine for pain Medica Database, treating DPN. acupuncture
relief in DPN. Sinomed, China combined with
 National Chinese herbal
Knowledge medicine as a
Infrastructure, complementary and
WanFang, and alternative
China Science medicine for DPN
and Technology
Journal Database
14 Effects of Examined the Semi- NGF, glycemic A combination of
hydrotherapy effects of experimental markers and hydrotherapy and
with massage on hydrotherapy and study dynamic balance massage enhances
serum nerve massage on NGF, four groups (three improved in AE, NGF concentrations,
growth factor balance and experimental AM and M groups; balance and the
concentrations glycemic groups and one however, the glycemic
and balance in markers in middle control group) increase profile compared to
middle aged aged DN patients. were randomly was greater hydrotherapy or
diabetic assigned and following the AM massage alone
neuropathy constructed to trial (p < 0.01)
patients answer the when compared to
Pouria Shourabi research the other trials.
et al. questions
(2020) proposed by the
investigative
research team
15 Aromatherapy examine the Randomized Neuropathic pain Aromatherapy
Massage for effects of controlled clinical scores significantly massage is a simple
Neuropathic Pain aromatherapy study decreased in the and effective
and Quality of massage The study sample intervention nonpharmacological
Life on neuropathic consisted of 46 group compared nursing intervention
in Diabetic pain severity and patients, with the control that can be used to
Patients quality of life randomly group in the fourth manage neuropathic
Zehra Gok (QoL) in patients allocated to an week of the study. pain and
Metin, et al. suffering from intervention Similarly, improve QoL in
(2017) painful diabetic group (n =21) and QoL scores patients with painful
neuropathy a control group (n significantly neuropathy
= 25). The improved in the
intervention intervention group
group received in the fourth
aromatherapy week of the study
massage three
times per week
for a period of 4
weeks.
16 Efficacy of Assess effect of Literature review Despite the positive Indicative of the
herbal medicine herbal medicine literature analysis findings, it is too effect of herbal
for patients with for patients with using articles that early to conclude medicine in reducing
diabetic diabetic were randomized on the efficacy of pain in diabetic
neuropathies: neuropathies. We controlled clinical herbal medicine to neuropathy.
An updated conducted a trials (RCTs). treat diabetic
literature review literature analysis Three databases neuropathy due to
Albert using articles that were the high clinical
Manggading were randomized searched from heterogeneity and
 Hutapea & controlled clinical PubMed, the number of
Boyke Marthin trials (RCTs). EMBASE, sample size of
Simbolon CENTRAL that the study was too
(2022) have been small
published from
January 2000
until October
2021until
October 2021
17 Hand and foot To investigate the Randomized For pain outcomes People with DPN in
exercises for effect of 8 weeks controlled trial Both groups have Myanmar can use
diabetic of simple hand, exercise decreased pain in these exercises to
peripheral finger, and foot (n = 51) and VAS and BRS prevent functional
neuropathy: exercises control (n = 53) throughout the data difficulties and
A randomized in patients with groups received collection. further complications
controlled trial diabetic peripheral usual care and Although there of DPN.
Mi Mi Thet Mon neuropathy diabetic foot carewere no significant
Win, et al. education; differences
(2019) only the exercise between
group performed and within groups,
exercises. the exercise group
had more decreased
pain in VAS than
the control.
18 Effect of This exploratory Randomised No differences in Preliminary data
Different analysis Controlled Trial sensory function suggests 8-weeks of
Exercise investigated Thirty-two were observed high-intensity
Training whether exercise inactive adults between groups. combined aerobic
Intensities on of different with T2D (59% Similar rates of and resistance
Musculoskeletal intensities leads to male, mean age adverse events exercise may be
and Neuropathic changes in self- 58.7±9.1yrs, were seen in both safely prescribed for
Pain in Inactive reported median HbA1c exercise inactive individuals
Individuals with musculoskeletal 7.8%) were interventions (19 with T2D and may
Type 2 Diabetes: pain or symptoms randomised to C-HIIT; 17 C- reduce
Preliminary of diabetic usual care (CON), MICT), all musculoskeletal pain
Randomised neuropathy in upervised but one of which but not neuropathic
Controlled Trial inactive combined aerobic were mild. symptoms
Emily R. Cox et individuals with and resistance
al. type 2 diabetes. moderate-
(2020) intensity
continuous
training (C-
MICT), or
supervised
combined
highintensity
interval training
(C-HIIT)
E. DISCUSSION

Electrical stimulation

Electrical stimulation is a therapy that delivers electricity to certain parts of the skin with the aim

of activating the nerves under the skin which are usually used to reduce pain symptoms such as

diabetic neuropathy (Adehunoluwa et al., 2019). In conducting electricity, it’s produces

paresthesias and / or blocks nerve fiber to produce an analgesic effects as occurs through

transctaneous electrical nerve stimulation (TENS) (Liampas et al., 2020). The electrical

stimulation therapies that found are Trancutaneous Electrical Nerve Stimulation (TENS),

Frequency-modulated electromagnetic neural stimulation (FREMS), percutaneous electrical nerve

stimulation (PENS) .

Trancutaneous Electrical Nerve Stimulation (TENS) in a study that was done by Tanmay and

Kathikeyan (2021) in patients with diabetic neuropathy pain who divided into 3 groups, they are

group A that received pain medications, group B that received pain medications and TENS, and

group 3 that received pain medications form doctor and Sham TENS. Each groups was observed

for 4 weeks and its found that group B who received pain medication and TENS was more

significant than group A and group C (Bose & Karthikeyan, 2021). A systemetic review study

about the use of non-pharmacological therapy in neuropathic pain that was done by Liampas, et

al.. (2020), found that in double-blind RCT trial by Bosi et al, applying Frequency-modulated

electromagnetic neural stimulation (FREMS) as monotherapy in patient with polyneuropathic

pain diabetes, found a statistically significant increase in pain intensity that can be resisted for at

least 4 months, and there’s also an analagesic effects, an improvement in quality of life, and a

significant improvement in motor nerve-conduction velocity (Liampas et al., 2020).

A systematic review study by Bernetti, et al. (2021) on international guidelines for neuropathy

from 6 articles found that TENS can be used to reduce diabetic neuropathic pain either early or

late and can be combined with psychotherapy and physiotherapy for neuropathic pain diabetic

(Bernetti et al., 2021).

Low Intensity Laser Therapy (LILT)

Low Intensity Laser Therapy (LILT) is a method of transmitting low-power waves in the range of

1-1000 mW, at waevelengths from 632-1064 nm. LILT can be a Helium Neon laser (HeeNe)

working at 632.8 nm, an Aluminum Gallium Arsenide (Al Ga As) laser or a diode laser working

at 780 - 830 nm (infrared light) and a Helium Neon diode laser. This method is cheap, effective,

and can be combined with the other methods (Chandran et al., 2020; Kaydok et al., 2020). In a

systematic review that was done by Anju, at a. (2019) regarding the use of LILT in diabetic

neuropathy patients, its greatly influences the reduction of diabetic neuroptahy pain. Of the 6

articles that has been discussed, there are 5 articles that reported the effectiveness of using LILT

for the management of diabetic neuropathy pain (Anju et al., 2019).

Low Intensity Laser Therapy (LILT) can be combined with electrical stimulation. A study of

systematic review that was performed to determine the effectiveness of electrical stimulation

which combined with LILT by Emannual, et al. (2019), proved tht its effective in the management

of Diabetic neuropathy pain (Adehunoluwa et al., 2019).

Repetitive Magnetic Stimulation

Transcranial Magnetic Stimulation (TMS) is a neurostimulation and neuromodulation technique,

based on the principle of electromagnetic induction of electric fields in the brain. The duratio n of

administration is very varied. The frequencies that used in TMS ranging from low frequencies (≤

1 Hz) produce inhibitions of motor cortical, while application of high frequency RTM (5-20 Hz)

causes long term inhibitory effects. This TMS is a safe and well-tolerated intervention (Aamir et

al., 2020; Liampas et al., 2020). Repetitive Transcranial Magnetik Stimulation (rTMS) has the

potential to reduce diabetic neuropathy pain. In a systematic review that was done by Aamir, et al.

(2019), neuropathic patient who gived rTMS therapy with a high frequency of 20 Hz from the

lower motor cortex for 3 weeks, has been shown to reduce the pain (Aamir et al., 2020).
Acceptance and Commitment Therapy (ACT)

Approaches to pain management with biopsychosocial therapy such as using Acceptance and

Commitment Therapy (ACT). ACT is a method of psychological intervention that aim to

increase opennes to the experience during the pain, changing behavior towards the pain, and how

to facilitate in the proccess of behavior changes. There are 6 stages in the ACT, that’s acceptance,

cognitive diffusion, action based on values, seeing the current situation, developing abilites and

seeing self potential (Hughes et al., 2017; Lin et al., 2019; Vowles et al., 2014). In dealing with

neuropathy pain, ACT can be used as in a study that was performed by Davoudi, et al (2020),

where ACT is used as an intervention for patients with neuropathic pain who experienced sleep

disorder and depression. The results of this study show that ACT can improve and refine

psychiatric problems in patients who experiece diabetic neuropathy pain. So that, outpatients need

to be given psychotherapy (Davoudi et al., 2020).

Acupuncture and Chines Herbal Medicine

Acupuncture is a Chinese medical practice that uses the flow of the body's vital energy known as

De Qi energy. De Qi energy is believed to be able to recover the bodies where when a needle

enters the skin, with or without needle menipulation on certain points of the body which can

stimulate sense of pain, numbness, and tingly (Mu et al., 2020; Xiang et al., 2017). In a study

about the effect of acupuncture on diabetic neuropathy pain that is done by Dietzel, et al (2021)

who using RCT method found that acupuncture may be considered effective and safe for diabetic

neuropathy patients (Dietzel et al., 2021).

Acupuncture with warm needles or Warm Neddle Accupunture (WNA) is an acupuncture

technique combined with moxibustion where this method is better because it increases blood flow

and reduces pain, compared to acupuncture or only moxibustion techniques (Wang et al., 2020).

A study of systematic review that is done by Nash, Jane et al.. (2019), explains that acupuncture

therapy was seen only improving symptoms. But the applications are still varied and the quality of

studies are still low, so further studies on effectiveness of acupuncture are needed with a better
methods. This is similar to the results of a systematic review study by Dimitrova, et al. (2017)

(Dimitrova et al., 2017; Nash et al., 2019). Acupuncture can be related to gate control theory

where pain input is inhibited by others painful stimuli (needling), and in a study it’s proved that

acupuncture stimulates the formation of anti-pain hormones that may reduced the pain. And

acupuncture is also closely related to phsychosocial, beliefs, expectations and environment

therapeutic (Mu et al., 2020).

Acupuncture therapy that combined with chinese herbs which was researched by Shi, et al (2021),

that the used of drugs hasn’t been standarized, so that in practice clinicians choose drugs based on

their experience. However, in a study on herbs for diabetic neuropathy pain by Hutapea and

Simbolon (2022) with a systematic review study on articles from 2000 to 2021, resulted that Gua

Sha therapy, green tea extractm and topical citrullus are effective to reduce neuropathic pain

(Hutapea & Simbolon, 2022).

Hydrotherapy

Hydrotherapy is one of the aquatic exercises such as pool therapy and balneotherapy.

Hydrotherapy is usually done in patients with neurological disorders and musculoskeletal

disorders. Hot water and buoyancy of water blocks nociceptors that works on thermal receptors

and mechanoreceptors, and have a positive effect on the spine. Warm water also improves blood

circulation and provides relaxing effect (Zamunér et al., 2019). Diabethic neuropathy pain

management with hydrotherapy that combined with massage is performed by Shourabi, et al.

(2020), with RCT method was implemented in 4 groups with a total pf 39 respondents. Group of

hydrotherapy (n=10), group of hydrotheraphy and massage (n=10), group of massage (n=10), and

group of control (n=19). From the results of eights weeks of activity, it was found in

Hydrotherapy groups that there’re improvement of Nerve Growth Factor (NGS) serum

concentration, a body balanced in a middle-aged adults respondents. However, hydrotheraphy that

is combined with massage has proved increase NGF and balance in general may improve the

glicemiec profile (Shourabi et al., 2020).

Aromatherapy massage

Aromatherapy is a complimentary therapy method that uses essential oils for therapy.

Aromatheraphy in studies has been shown to have benefots against pain, anxiety, depression,

cognitive functions, and sleep disorders in the elderly (Pehlivan & Karadakovan, 2019). Massage

combine with lavender aromatherapy was applied to patients with osteoathrtis pain was proven to

be effective in reducing the incidence in daily activities (Nasiri & Mahmodi, 2018). Study on the

effects of aromatherapy massage on neuropathic pain and quality of life for diabetic neuropathy,

is done by Metin, et al. (2017) using RCT method with 46 respondents that divided into 21

respondents in the intervention group, and 25 in the control group which was performed for 4

weeks. Statistical results in this study showed that massage aromatherapy was proven to reduce

pain in 4 weeks (p < 0,000), and improve quality if life (p < 0,049) (Gok Metin et al., 2017).

Exercises Tranining

Exercises Training is a physical exercise (Physical Activity) according to WHO (2020) is all

physical activity of body movement that uses muscles and requires energy, where this activity can

reduce depression and anxiety and can be used in the prevention and management of heart

disease, cancer and diabetes. A study that conducted by Cox, et al. (2020) about the differences in

the intencity of physical exercise in patients with musculoskeletal pain and neuropathic pain in

patient with type 2 diabetes, which was cariied out for 8 weeks. The number of respondents are 32

people an divided into three groups, that’s CON Groups (n=12), C-MICT group (n=10), and C-

HIIT group (n=10). From the results of researches for 8 weeks, obtained results of the effect on

the intensity of muscoskeletal pain and neuropathic pain C-HIIT intervention (MD -5.4, 95% CI

-10.6 to -0.2, p=0.041), had a big effects on reducing pain comapred to the CON nd C-MICT.

Meanwhile, the effects on the sensory function by all interventions had no significant effects

(p>0.05) (Cox et al., 2020).

Another study (Win, et al. 2018) on exercise training with hand and foot exercises for patient with

neuropathic pain with an RCT study has been researched in two different groups 16 weeks, they
 are intervention group (exercise program; hand, finger, and foot) (n=15) and control group

(n=53). The results are in the intervetion group , there was significant improvement of motor and

specific activities (p = 0.041), the severity during exercise period of both groups had no

significant difference, in the relation to pain, both has no significant difference, but the

intervention group had a significant reduction in pain compared to the control group (Win et al.,

2020).

F. CONCLUSION

Non-pharmacological therapy that are proven to be able to reduce neuropathic pain in diabetic

patients are electrical stimulation, low intensity laser therapy (LILT), repetitive magnetic

stimulation, acceptance and commitment therapy (ACT), hydrotherapy, aromatherapy massage,

exercises training, accupunture dan chinese herbs medicine. The articles that found in this

systematic review are were still varied, so it’s cannot be used as meta analyses. The limits by the

use of search engine to access international based data, allow us to missed others studies so that

can’t be published in this study. Research using an RCT method about types of non-

pharmacological therapy to reduce diabetic neuropathy pain with large sample are necessary to do

so that generalizations can be achieved.

References

Aamir, A., Girach, A., Sarrigiannis, P. G., Hadjivassiliou, M., Paladini, A., Varrassi, G., & Zis, P.

(2020). Repetitive Magnetic Stimulation for the Management of Peripheral Neuropathic Pain: A

Systematic Review. Advances in Therapy, 37(3), 998–1012. https://doi.org/10.1007/s12325-020-

01231-2

Adehunoluwa, E. A., Adesina, M. A., Adeulure, T. G., Akinfolarin, Y. T., Babatunde, K. O.,

Efunniyi, A. O., Mamud, O. S., Oyejola, O. G., Tiamiyu, O. M., & Olajire, T. I. (2019).

Effectiveness of electrical stimulation and low-intensity laser therapy on diabetic neuropathy: A

systematic review. World News of Natural Sciences, 23(January), 110–127.

Anju, M., Ummer V, S., Maiya, A. G., & Hande, M. (2019). Low level laser therapy for the patients

with painful diabetic peripheral neuropathy - A systematic review. Diabetes and Metabolic

Syndrome: Clinical Research and Reviews, 13(4), 2667–2670.

https://doi.org/10.1016/j.dsx.2019.07.035

Bernetti, A., Agostini, F., de Sire, A., Mangone, M., Tognolo, L., Di Cesare, A., Ruiu, P., Paolucci,

T., Invernizzi, M., & Paoloni, M. (2021). Neuropathic pain and rehabilitation: A systematic

review of international guidelines. Diagnostics, 11(1), 1–10.

https://doi.org/10.3390/diagnostics11010074

Bose, T. K., & Karthikeyan, M. (2021). International Journal of Research Publication and Reviews

Effectiveness of Transcutaneous Electrical Nerve Stimulation In Chronic Painful Diabetic

Neuropathy. 2, 22–29.

Brunner, & Suddarth. (2022). Keperawatan Medikal Bedah (D. Yulianti & A. Kimin (eds.); 12th ed.).

EGC.

Chandran, N., Muralidhar, N. V., Suma, S., Shashikumar, P., & Raghunath, N. (2020). Comparing the

effect of low-intensity laser therapy (LILT) in decrowding lower anteriors using conventional

and self-ligating MBT bracket systems - An in vivo study. Biomedical and Pharmacology

Journal, 13(1), 159–166. https://doi.org/10.13005/bpj/1872

Cox, E. R., Gajanand, T., Burton, N. W., Coombes, J. S., & Coombes, B. K. (2020). Effect of

different exercise training intensities on musculoskeletal and neuropathic pain in inactive

individuals with type 2 diabetes – Preliminary randomised controlled trial. Diabetes Research

and Clinical Practice, 164, 108168. https://doi.org/10.1016/j.diabres.2020.108168

Davoudi, M., Taheri, A. A., Foroughi, A. A., Ahmadi, S. M., & Heshmati, K. (2020). Effectiveness of

acceptance and commitment therapy (ACT) on depression and sleep quality in painful diabetic

neuropathy: a randomized clinical trial. Journal of Diabetes and Metabolic Disorders, 19(2),

1081–1088. https://doi.org/10.1007/s40200-020-00609-x

Dietzel, J., Hörder, S., Habermann, I. V., Meyer-Hamme, G., Hahn, K., Ortiz, M., Roll, S., Linde, K.,

Irnich, D., Hammes, M., Nögel, R., Wullinger, M., Wortman, V., Hummelsberger, J., Willich, S.

N., Schröder, S., & Brinkhaus, B. (2021). Acupuncture in diabetic peripheral neuropathy—

protocol for the randomized, multicenter ACUDPN trial. Trials, 22(1), 1–12.

https://doi.org/10.1186/s13063-021-05110-1

Dimitrova, A., Murchison, C., & Oken, B. (2017). Acupuncture for the Treatment of Peripheral

Neuropathy: A Systematic Review and Meta-Analysis. Journal of Alternative and

Complementary Medicine, 23(3), 164–179. https://doi.org/10.1089/acm.2016.0155

Gok Metin, Z., Arikan Donmez, A., Izgu, N., Ozdemir, L., & Arslan, I. E. (2017). Aromatherapy

Massage for Neuropathic Pain and Quality of Life in Diabetic Patients. Journal of Nursing

Scholarship, 49(4), 379–388. https://doi.org/10.1111/jnu.12300

Gylfadottir, S. S., Christensen, D. H., Nicolaisen, S. K., Andersen, H., Callaghan, B. C., Itani, M.,

Khan, K. S., Kristensen, A. G., Nielsen, J. S., Sindrup, S. H., Andersen, N. T., Jensen, T. S.,

Thomsen, R. W., & Finnerup, N. B. (2020). Diabetic polyneuropathy and pain, prevalence, and

patient characteristics: A cross-sectional questionnaire study of 5,514 patients with recently

diagnosed type 2 diabetes. In Pain (Vol. 161, Issue 3).

https://doi.org/10.1097/j.pain.0000000000001744

Hinkle, J. L., & Cheever, K. H. (2018). Brunnert and Suddarth’s textbook of Medical-Surgical
 Nursing (S. Kellie (ed.); 14th editi). Julie K. Stegman.

Huang, K.-L., Wang, S.-Y., Lu, W.-C., Chang, Y.-H., Su, J., & Lu, Y.-T. (2019). Effects of low-dose

computed tomography on lung cancer screening: a systematic review, meta-analysis, and trial

sequential analysis. BMC Pulmonary Medicine, 19(1), 126. https://doi.org/10.1186/s12890-019-

0883-x

Hughes, L. S., Clark, J., Colclough, J. A., Dale, E., & McMillan, D. (2017). Acceptance and

Commitment Therapy (ACT) for Chronic Pain. Clinical Journal of Pain, 33(6), 552–568.

https://doi.org/10.1097/AJP.0000000000000425

Hutapea, A. M., & Simbolon, B. M. (2022). Efficacy of herbal medicine for patients with diabetic

neuropathies: An updated literature review. Biomedicine, 42(2), 209–213.

https://doi.org/10.51248/.v42i2.1346

IDF. (2021). International Diabetes Federation. In P. Riley, B. J. Edward, D. J. Magliano, S.

Karurangga, & L. Piemonte (Eds.), IDF Diabetes Atlas, 9th edition (10th ed.).

https://diabetesatlas.org/idfawp/resource-files/2019/07/IDF_diabetes_atlas_ninth_edition_en.pdf

Jaiswal, M., Divers, J., Dabelea, D., Isom, S., Bell, R. A., Martin, C. L., Pettitt, D. J., Saydah, S.,

Pihoker, C., Standiford, D. A., Dolan, L. M., Marcovina, S., Linder, B., Liese, A. D., Pop-Busui,

R., & Feldman, E. L. (2017). Prevalence of and risk factors for diabetic peripheralneuropathy in

youth with type 1 and type 2 diabetes: Search for diabetes in youth study. Diabetes Care, 40(9),

1226–1232. https://doi.org/10.2337/dc17-0179

Kaydok, E., Ordahan, B., Solum, S., & Karahan, A. Y. (2020). Short-term efficacy comparison of

high-intensity and low-intensity laser therapy in the treatment of lateral epicondylitis: A

randomized double-blind clinical study. Archives of Rheumatology, 35(1), 60–67.

https://doi.org/10.5606/ArchRheumatol.2020.7347

Kemenkes. (2020). Infodatin tetap produktif, cegah, dan atasi Diabetes Melitus 2020. In Pusat Data

dan Informasi Kementrian Kesehatan RI (pp. 1–10).

https://pusdatin.kemkes.go.id/resources/download/pusdatin/infodatin/Infodatin-2020-Diabetes-
 Melitus.pdf

Liampas, A., Rekatsina, M., Vadalouca, A., Paladini, A., Varrassi, G., & Zis, P. (2020). Non-

Pharmacological Management of Painful Peripheral Neuropathies: A Systematic Review.

Advances in Therapy, 37(10), 4096–4106. https://doi.org/10.1007/s12325-020-01462-3

Lin, J., Scott, W., Carpenter, L., Norton, S., Domhardt, M., Baumeister, H., & McCracken, L. M.

(2019). Acceptance and commitment therapy for chronic pain: Protocol of a systematic review

and individual participant data meta-Analysis. Systematic Reviews, 8(1), 1–10.

https://doi.org/10.1186/s13643-019-1044-2

Mu, J., Furlan, A. D., Lam, W. Y., Hsu, M. Y., Ning, Z., & Lao, L. (2020). Acupuncture for chronic

nonspecific low back pain. Cochrane Database of Systematic Reviews, 2020(12).

https://doi.org/10.1002/14651858.CD013814

Nash, J., Armour, M., & Penkala, S. (2019). Acupuncture for the treatment of lower limb diabetic

peripheral neuropathy: a systematic review. In Acupuncture in Medicine (Vol. 37, Issue 1, pp. 3–

15). https://doi.org/10.1136/acupmed-2018-011666

Nasiri, A., & Mahmodi, M. A. (2018). Aromatherapy massage with lavender essential oil and the

prevention of disability in ADL in patients with osteoarthritis of the knee: A randomized

controlled clinical trial. Complementary Therapies in Clinical Practice, 30, 116–121.

https://doi.org/10.1016/j.ctcp.2017.12.012

Pehlivan, S., & Karadakovan, A. (2019). Effects of aromatherapy massage on pain, functional state,

and quality of life in an elderly individual with knee osteoarthritis. Japan Journal of Nursing

Science, 16(4), 450–458. https://doi.org/10.1111/jjns.12254

Pranata, S. (2017). Perbedaan Tingkat Kecemasan Pada Pasien Diabetes Melitus Dengan Neuropati

Perifer Yang Diberikan Intervensi Tens Dan Intervensi Nafas Dalam Saat Dilakukan Perawatan

Ulkus Kaki Diabetik Di Rsud Kota Yogyakarta. Jurnal Keperawatan Dan Pemikiran Ilmiah,

3(2), 11–19. http://jurnal.unissula.ac.id/index.php/jnm/article/view/2267/1712

Ren, L., Guo, R., Fu, G., Zhang, J., & Wang, Q. (2022). The efficacy and safety of massage adjuvant
 therapy in the treatment of diabetic peripheral neuropathy. Medicine, 101(10), e29032.

https://doi.org/10.1097/md.0000000000029032

Shi, Y., Liu, L., Sun, X., & Jiao, J. (2021). Efficacy and safety of acupuncture combined Chinese

herbal medicine for diabetic peripheral neuropathy. Medicine (United States), 100(50), E28086.

https://doi.org/10.1097/MD.0000000000028086

Shillo, P., Sloan, G., Greig, M., Hunt, L., Selvarajah, D., Elliott, J., Gandhi, R., Wilkinson, I. D., &

Tesfaye, S. (2019). Painful and Painless Diabetic Neuropathies: What Is the Difference? In

Current Diabetes Reports (Vol. 19, Issue 6). https://doi.org/10.1007/s11892-019-1150-5

Shourabi, P., Bagheri, R., Ashtary-Larky, D., Wong, A., Motevalli, M. S., Hedayati, A., Baker, J. S.,

& Rashidlamir, A. (2020). Effects of hydrotherapy with massage on serum nerve growth factor

concentrations and balance in middle aged diabetic neuropathy patients. Complementary

Therapies in Clinical Practice, 39, 101141. https://doi.org/10.1016/J.CTCP.2020.101141

Sobhy, T. (2016). The Need for Improved Management of Painful Diabetic Neuropathy in Primary

Care. 2016.

Suwondo, B. S., Meliala, L., & Sudadi. (2017). Buku Ajar Nyeri 2017.

https://id.scribd.com/document/401666306/EBOOK-BUKU-AJAR-NYERI-R31JAN2019-pdf

Vowles, K. E., Fink, B. C., & Cohen, L. L. (2014). Acceptance and Commitment Therapy for chronic

pain: A diary study of treatment process in relation to reliable change in disability. Journal of

Contextual Behavioral Science, 3(2), 74–80. https://doi.org/10.1016/j.jcbs.2014.04.003

Wang, L. Q., Wang, F., & Wang, X. H. (2020). Effectiveness of warm needling acupuncture for pain

relief in patients with diabetic peripheral neuropathy: A protocol of systematic review. Medicine,

99(45), e23077. https://doi.org/10.1097/MD.0000000000023077

Win, M. M. T. M., Fukai, K., Nyunt, H. H., & Linn, K. Z. (2020). Hand and foot exercises for

diabetic peripheral neuropathy: A randomized controlled trial. Nursing and Health Sciences,

22(2), 416–426. https://doi.org/10.1111/nhs.12676

Xiang, A., Cheng, K., Shen, X., Xu, P., & Liu, S. (2017). The Immediate Analgesic Effect of
 Acupuncture for Pain: A Systematic Review and Meta-Analysis. Evidence-Based

Complementary and Alternative Medicine, 2017. https://doi.org/10.1155/2017/3837194

Zamunér, A. R., Andrade, C. P., Arca, E. A., & Avila, M. A. (2019). Impact of water therapy on pain

management in patients with fibromyalgia: Current perspectives. Journal of Pain Research, 12,

1971–2007. https://doi.org/10.2147/JPR.S161494