Electroacupuncture May Improve Burning and Electric Shock-Like Neuropathic Pain: A Prospective Exploratory Pilot Study

Abstract

Objective:

To test the effectiveness of electroacupuncture (EA) for managing intractable neuropathic pain (NeP) and assess the protocol for a larger confirmatory trial.

Design:

A prospective, multicenter, single-armed, add-on, pilot study.

Settings/location:

At two tertiary university-based hospitals in Seoul, Republic of Korea.

Subjects:

Patients with chronic peripheral NeP, who have received conventional oral medications but complained of moderate to severe pain.

Interventions:

Two Korean medicine doctors conducted 12 sessions of EA (2 sessions per week for 4 weeks, followed by 1 session per week for the second month) in addition to conventional treatment.

Outcome measures:

During the 8-week treatment period, pain intensity, pain natures such as burning, electric shock-like, temperature or mechanical hyperalgesia, and numbness, Short Form of the McGill Pain Questionnaire (SF-MPQ) and the Brief Pain Inventory (BPI-SF), the EuroQol five dimensions questionnaire, patients' satisfaction, and adverse events were evaluated. The primary endpoint was a change in pain intensity (%) at 4 weeks from the baseline.

Results:

Among 22 patients, 19 finished the protocol. The eight EA sessions over a month reduced pain intensity from 6.0 ± 1.6 at baseline to 3.2 ± 0.9 at 4 weeks, which was a 46.7% reduction (p < 0.001). The incidences of severe burning, electric shock-like pain, and mechanical hyperalgesia reduced at 8 weeks [36%–16% (p = 0.04), 53%–21% (p = 0.009), and 53%–26% (p = 0.03), respectively]. The affective dimensions in the SF-MPQ (p = 0.007) and the pain interference parameters, including mood (p = 0.02), relations with other people (p = 0.03), and enjoyment of life (p = 0.002) in the BPI-SF, were improved at 4 and 8 weeks. The majority of patients (68%) responded that their pain was “much or somewhat improved.” Overall, 84.2% expressed “satisfaction” with their multidisciplinary management.

Conclusions:

EA might decrease the intensity of NeP, in particular, such as burning, electric shock-like pain, and mechanical hyperalgesia, which was accompanied by psychosocial and functional improvement. A larger study is warranted to prove the effectiveness of EA for managing refractory NeP.

Trial registration:

ClinicalTrials.gov: NCT03315598. Retrospectively registered on October 20, 2017.

Introduction

Neuropathic pain (NeP) is a disease of the somatosensory nervous system, with a prevalence of 6.9%–10% in the overall population.^1
–3 The management of NeP is challenging due to its severe intensity, various symptoms, and chronicity. Pharmacotherapy has involved the use of antidepressants and anticonvulsants in NeP.^4,5 However, even after long-term use of them, only half the patients were satisfied with their management.^6
–8 Furthermore, frequent comorbidities accompanied by NeP conditions, such as sleep disorders, anxiety, and depression, have those patients steer to the vicious cycle with a poor quality of life (QoL).⁴

Among a plethora of alternatives for pain management, acupuncture is one of the popular treatment options. A recent systematic review with 17,922 patients indicated that acupuncture was effective for chronic pain, which was better than a placebo.⁹ Besides, the American College of Physicians has recommended it as a nonpharmacological treatment choice for both acute and chronic low back pain.¹⁰ Animal studies have proposed some mechanisms of acupuncture as segmental analgesia¹¹ or by strengthening descending inhibition,^12,13 releasing opioid peptides in the spinal perfusate,^13,14 and binding to adenosine A1 receptors.^15,16 However, little evidence exists in acupuncture for managing NeP.^17,18 Although potential advantages were reported in a combination of acupuncture with other treatments, such as Xiaoke bitong in painful diabetic neuropathy¹⁹ or methylcobalamin in chemotherapy-induced peripheral neuropathy (CIPN),²⁰ questions have revolved around whether acupuncture is efficient when combined with anticonvulsants and antidepressants.

Therefore, we hypothesized that acupuncture had a clinical benefit in the management of NeP when added to conventional NeP pharmacotherapy. In this prospective multicenter pilot study, we performed electroacupuncture (EA), a type of acupuncture in which a small electrical charge is applied to needles, in patients with chronic intractable NeP. The study aimed to test the improvement of NeP and to assess the feasibility of the protocol in preparation for a larger clinical trial.

Materials and Methods

This trial was approved by the Institutional Review Board (IRB) of the Seoul National University Hospital (SNUH IRB No. 0720-171-071) and the Kyung Hee University Korean Medicine Hospital (KOMCIRB-170410-HR-010), and it was conducted in accordance with the Declaration of Helsinki and the Korean Good Clinical Practice Guidelines. This prospective, open-label, multicenter, pilot trial was registered in ClinicalTrials (NCT03315598). Patients were enrolled from May 2017 to March 2018 after obtaining study consents.

Inclusion criteria were as follows: (1) patients aged ≥19 years, who had chronic peripheral neuropathy, such as postherpetic neuralgia (PHN), failed back surgery syndrome (FBSS), CIPN, or other peripheral neuropathy confirmed by electromyography and nerve conduction velocity testing; (2) a score ≥4 on the 11-pointed numerical rating scale (NRS) pain score (0 = no pain and 10 = worst possible pain) for ≥3 months despite the management with oral antidepressants and anticonvulsants medications; (3) a score ≥19 on the Korean version of the painDETECT²¹; (4) no changes in the medication regimen for the past 1 month; (5) no invasive pain interventions (acupuncture, peripheral nerve blocks, epidural injections, etc.) within the past 1 month; (6) an average NRS pain score ≥4/10 during the 1-week screening period.

Patients with one of the following conditions were excluded: (1) any other pain that was considerably greater than NeP; (2) major mental illness or brain damage; (3) implanted medical devices such as spinal cord stimulators; (4) abnormal skin conditions that may prevent the EA treatment; (5) participation in other clinical trials within the last 4 weeks; (6) pregnant, breastfeeding, or additional medical conditions, which were regarded as inadequate for participation.

Intervention

This study included a 7-day screening period and a 2-month EA treatment period (Fig. 1). First, patients who met inclusion criteria were screened at the initial visit (V1) at Seoul National University Hospital (SNUH) Pain Center. Patients were asked to record pain diaries with daily average NRS pain scores for a 1-week screening period. If a patient still met the inclusion criteria at visit 2 (V2, baseline) and reported a score ≥19 on the painDETECT, they were scheduled to undergo 12 sessions of EA for 8 weeks at the Kyung Hee University Korean Medicine Hospital (KHUKMH). EA was done twice per week for the first 4 weeks and once per week for the following 4 weeks. In addition, the patients continued to intake the same types and dosages of their oral medications, including anticonvulsants and antidepressants, as well as antianxiolytics, opioids, tramadol, nonsteroidal anti-inflammatory drugs, muscle relaxants, prostaglandin, Vitamin B1 and B12, and nefopam. Nerve block, laser therapy, other electrical therapy, and any physical therapies were prohibited during the period. Acetaminophen was allowed as a rescue medication with a maximum of 3 g per day. Patients were encouraged to record daily average NRS pain scores in their pain diaries throughout the study. The outcome measures were evaluated at 4 (V3) and 8 weeks (V4) by one research nurse at the SNUH, who was independent of the study.

FIG. 1.

Study design patients were screened, enrolled, and evaluated in Hospital A. All EA treatments were performed in Hospital B. EA, electroacupuncture; V, visit number.

EA treatment was administered by two Korean medicine doctors (KMDs; S.L. and J.K.) having 6 years of Korean medicine college education and at least 8 years of clinical experiences at the KHUKMH. The EA interventions were conducted according to a consensus of acupuncture specialists based on the Western medical acupuncture techniques as well as the Korean traditional medicine meridian theory, which were described in the Standards for Reporting of Controlled Trials in Acupuncture (STRICTA) recommendations.²² A total of 12 acupuncture treatments were performed during the 8-week treatment period with 0.25 × 40 mm disposable sterile acupuncture needles (Dongbang Acupuncture, Inc., Chungnam, South Korea), which were retained for 20 min. After penetration, de qi sensation was induced using reinforcing-reducing techniques such as the rotating and lifting-thrusting methods. The acupuncture points were determined by the consensus of the acupuncture experts (S.L., J.K., and S.H.L.), which were selected individually on the basis of traditional acupuncture theory and neurophysiological perspectives,²³ according to the following guidelines:

local points: two to eight points near the painful region as a classical acupuncture point, tender point, or trigger point.

segmental points: two to eight points innervated by the same meridian or spinal nerve as that of the painful region, such as BL40–BL57 on the lower limb for FBSS, LI11–LI10 on the upper limb for CIPN, or Hua-Tuo-Jia-Ji-Xue on the paraspinal muscles for PHN. Points close to the affected segment, such as those above and below the area, or those on the opposite side of the equivalent contralateral segment to be chosen as perisegmental points if direct needling aggravated the pain.

distal points: one to eight points that are not in or close to a segmental region on the contralateral side of the body or extremities. Distal points were selected to treat the general symptoms commonly observed in conjunction with chronic pain, such as insomnia (PC6, HT7, BL62, or KI6), depression/anxiety (PC6, HT7, LI4, or SP6), or fatigue (ST36, SP6, LU8, or GB20).

EA was performed at up to eight points among the aforementioned local, segmental, and distal points. An EA device (ES-160; Ito Co., Ltd. Tokyo, Japan) was used to apply 2/6 Hz (altering every 2 sec) or 100 Hz with titration to ∼80% of the maximum intensity that the patient could endure as “moderately strong but not painful” (Supplementary Fig. S1).

Outcome measures

The primary endpoint was a change in the pain intensity (%) at V3 (4 weeks) from the baseline (V2) using the average NRS pain score of the last 1 week. The secondary endpoints were as follows: (1) changes in the NRS pain score at V4 (8 weeks) from the baseline (V2); (2) changes in NeP characteristics, such as burning, electric shock-like, and cold or heat-evoked pain, numbness, and pain with slight pressure at V3 and V4 from the baseline, using a 6-point Likert scale scored from 0 (never) to 5 (very strongly); (3) changes in the Short-Form McGill Pain Questionnaire (SF-MPQ)²⁴ scores at V3 and V4 from the baseline, which included the present pain intensity (PPI) and 15 questionnaires (11 for the sensory dimension of pain experience and 4 for the affective dimension; each descriptor was ranked on an intensity scale ranged from 0 = none to 3 = severe); (4) changes in the Short Form of the Brief Pain Inventory (BPI-SF)²⁵ at V3 and V4 from the baseline, which measured the impact of pain on the patient's daily functioning using nine items, each having seven components and scored from 0 (no interference) to 10 (interferes completely); (5) changes in the EuroQol five dimensions questionnaire (EQ-5D) at V3 and V4 from the baseline, which evaluated five dimensions including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and calculates a single EQ-5D index-based utility score on a scale of −0.59 to 1.00, with 1.00 indicating full health and 0 equal to death^26,27; (6) Patient Global Impression of Change (PGIC) scores at V4, which was assessed using a 7-point Likert scale scored from 1 (very much improved) to 7 (very much worsened); and (7) a 5-point patient satisfaction score with EA treatment and the collaborative treatment for NeP management, which ranged from 1 (extremely satisfied) to 5 (extremely dissatisfied) at V4.

At each visit, patients were asked to report any adverse events associated with EA throughout the study period, including procedure-related pain, bruising, bleeding, or infection at the local site and nausea, dizziness, or anxiety.²³

Statistical analysis

Based on the previous pilot study,²⁸ at least 20 patients were needed for the analysis in this exploratory study. When considering a 30% dropout rate, 29 patients should be finally enrolled. For the feasibility test, the recruitment rate was calculated as the total number of patients divided by the number of months recruiting. The compliance rate was measured by the number of acupuncture sessions that patients completed over the theoretical maximum number of scheduled acupuncture sessions.

Outcome analyses were performed on the per-protocol population for the primary endpoint and the secondary endpoints. Safety analysis was based on the intent-to-treat population. For analysis of the primary endpoint, the Wilcoxon signed-rank test was used to assess the statistical significance of the differences (%) in the average NRS pain scores between the V2 (at baseline) and V3 (at 4 weeks). For analysis of the secondary endpoints, changes in the average NRS pain scores at V4 (at 8 weeks) from the V2 (at baseline) were analyzed using the Wilcoxon signed-rank test. In terms of NeP characteristics, we compared incidences (%) of “strongly” and “very strongly” noticed symptoms between the baseline (V2) and the follow-ups (at V3 and V4) using the Friedman test with the Bonferroni adjustment (an adjusted p < 0.025 was considered statistically significant). The SF-MPQ, BPI-SF, and EQ-5D scores between baseline and V3 or V4 were compared using the Friedman test, following Bonferroni correction in post hoc analysis.

Data were analyzed using SPSS version 22.0 software (IBM Corp, Armonk, NY) for Windows. Outcomes were shown as mean ± standard deviation or frequency (%) as appropriate. A p-value <0.05 was considered statistically significant.

Results

Among 29 patients who were screened over 7 months, seven were excluded due to low painDETECT scores (n = 4) and withdrawal of consent before starting the EA treatment (n = 3); thus, 22 patients started with EA treatment (recruitment rate = 3.1 patients per month). Then, three patients were excluded due to changes made in the type of oral medication by other physicians (n = 2) and loss of the pain diary at 4 weeks (n = 1) (dropout rate = 13.6%) (Fig. 2). During the study period, a total of 257 EA treatments were conducted in 22 patients, which represented 11.7 sessions per patient, with a 97.3% of a compliance rate.

FIG. 2.

Flowchart of the study.

Demographics are described in Table 1. PHN (n = 7) was the most common diagnosis, followed by CIPN (n = 4). The average pain duration was >3 years with a moderate intensity of the pain (average NRS = 6.0). Overall, two-thirds (n = 14) were managed with calcium channel blockers and one-third (n = 7) with tricyclic antidepressants for managing the NeP. The average painDETECT score was 22.7 ± 2.8, suggesting “a clear diagnosis of the presence of a NeP component.”²¹

Table 1.

Demographics and Clinical Characteristics

	Enrolled (n = 29)	Completed (n = 19)
Sex (male/female)	13 (44.8%)/16 (55.2%)	5 (26.3%)/14 (73.7%)
Age (years)	59.2 ± 11.8	58.9 ± 11.0
Height (cm)	162.2 ± 10.6	161.2 ± 10.8
Weight (kg)	63.4 ± 11.9	62.2 ± 10.6
Comorbidities
Diabetes mellitus	6 (20.7%)	4 (21.1%)
Hypertension	9 (31.0%)	5 (26.3%)
Cancer	1 (3.4%)	0 (0.0%)
Diagnosis
PHN	9 (31.0%)	7 (36.8%)
CIPN	6 (20.7%)	4 (21.1%)
Occipital neuralgia	5 (17.2%)	3 (15.8%)
FBSS	3 (10.3%)	2 (15.8%)
Diabetic neuropathy	1 (3.4)	0 (0.0%)
Other mononeuropathy	5 (17.2%)	3 (26.3%)^a
Pain duration (months)	35.8 ± 35.8	42.6 ± 39.1
Pain intensity (11-point NRS score)	5.9 ± 1.8	6.0 ± 1.6
Medications
Anticonvulsants	19 (65.5%)	14 (73.7%)
Antidepressants	10 (52.6%)	7 (36.8%)
Benzodiazepine	2 (6.9%)	1 (5.3%)
Analgesics (non-opioids)	13 (44.8%)	9 (47.4%)
Opioids	5 (26.3%)	3 (15.8%)

Other mononeuropathy included carpal tunnel syndrome with median neuropathy (n = 1), meralgia paresthetica with lateral femoral cutaneous neuropathy (n = 1), and tarsal tunnel syndrome with posterior tibial neuropathy (n = 1).

CIPN, chemotherapy-induced peripheral neuropathy; FBSS, failed back surgery syndrome; NRS, numerical rating scale; PHN, postherpetic neuralgia.

The primary endpoint is given in Figure 3. The baseline NRS pain score decreased from 6.0 ± 1.6 at baseline to 3.2 ± 0.9 at V3, which was a 46.7% reduction at 4 weeks (p < 0.001). Although the NRS pain score increased at 8 weeks (5.3 ± 1.8) compared with that at 4 weeks, it was still significantly lower than the baseline (12.1% of reduction at V4; p = 0.009).

FIG. 3.

Changes in the 11-point NRS pain scores during 12 sessions of electroacupuncture treatment The baseline NRS pain score decreased from 6.0 ± 1.6 at baseline to 3.2 ± 0.9 at 4 weeks and 5.3 ± 1.8 at 8 weeks. NRS, numerical rating scale.

Concerning the NeP traits, incidences of severe “burning,” “electric shock-like pain,” and “pain with slight pressure” were significantly decreased at V3 and V4 (Table 2). With regard to SF-MPQ, the PPI and the affective dimensions, including “fear” and “punishing-cruel,” were significantly improved as well. In terms of BPI-SF, the PPI, mood, relations with other people, and enjoyment of life were enhanced at V3 and V4. There was a significant improvement in the EQ-5D index at V4 compared with the baseline, whereas no significance existed at V3.

Table 2.

Details of Results in the Short-Form McGill Pain Questionnaire, Short Form of Brief Pain Inventory, EuroQol Five Dimensions Questionnaire, and the Nature of Neuropathic Pain

Items	Baseline	4 weeks	8 weeks	p-Value
SF-MPQ
Total score	23.8 ± 8.9	19.3 ± 7.9 (19%)	18.8 ± 7.4 (21%)	0.11
Sensory score	17.8 ± 6.2	14.8 ± 6.2 (17%)	14.9 ± 5.5 (16%)	0.16
Affective score	6.0 ± 3.1	4.5 ± 2.5^* (25%)	3.9 ± 2.4^* (27%)	0.007
PPI	2.7 ± 0.7	2.1 ± 0.7^** (22%)	2.1 ± 0.6^* (22%)	0.001
BPI-SF
PIS	6.2 ± 2.0	5.1 ± 1.4^* (18%)	5.0 ± 1.4^* (19%)	0.02
General activity	6.1 ± 2.0	5.2 ± 1.7 (15%)	5.2 ± 1.4 (15%)	0.32
Mood	7.2 ± 1.8	6.0 ± 1.7 (17%)	6.3 ± 2.0 (13%)	0.02
Walking ability	5.4 ± 3.1	3.9 ± 2.4^* (28%)	3.6 ± 2.4 (33%)	0.14
Normal work	6.3 ± 2.3	5.3 ± 2.1 (16%)	5.2 ± 1.6 (17%)	0.20
Relations with other people	5.8 ± 2.5	4.8 ± 1.7 (17%)	4.4 ± 2.1 (24%)	0.03
Sleep	6.2 ± 2.8	5.2 ± 2.8^* (16%)	5.1 ± 2.5 (18%)	0.11
Enjoyment of life	6.8 ± 2.3	5.3 ± 1.9^** (22%)	5.2 ± 2.0^* (24%)	0.002
EQ-5D index	0.52 ± 0.18	0.55 ± 0.18 (5%)	0.63 ± 0.12^* (20%)	0.02
Severe intensity of NeP nature^a
Burning	7 (36%)	3 (16%)	3 (16%)	0.04
Electric shock-like pain	10 (53%)	6 (40%)	4 (21%)	0.009
Pain by cold or heat	4 (21%)	4 (21%)	3 (16%)	0.78
Numbness	8 (42%)	4 (21%)	5 (26%)	0.24
Pain by slight pressure	10 (53%)	6 (32%)	5 (26%)	0.03

Data are given as mean ± standard deviation (improvement %) or an incidence (%).

Bonferroni-corrected clinical significance at each visit: ^*<0.025, ^** <0.005.

NeP nature was evaluated using a 6-point Likert scale (0 = never; 1 = hardly noticed; 2 = slightly; 3 = moderately; 4 = strongly; and 5 = very strongly); out of them, the severe intensity of NeP nature was defined as responses with 4 (strongly) or 5 (very strongly).

BPI-SF, Short Form of the Brief Pain Inventory; EQ-5D, EuroQol five dimensions questionnaire; NeP, neuropathic pain; PIS, Pain Interference Scale; PPI, present pain intensity; SF-MPQ, Short-Form McGill Pain Questionnaire.

Regarding PGIC, two-thirds of patients (n = 13, 68.4%) responded that their pain was “much or somewhat improved” at V4, whereas no patient answered that their pain “worsened.” In addition, the majority of patients (n = 13, 68.4%) responded that they were “extremely satisfied” or “somewhat satisfied” with EA treatment at V4. Concerning the collaborative treatment of NeP by a pain physician and a KMD, the majority (n = 16, 84.2%) replied “extremely satisfied” or “somewhat satisfied” at the final visit (V4).

Among 22 patients who underwent EA treatment even once or more, no severe complication was reported. Two patients reported minor adverse events such as dizziness (n = 1) and freezing sensation (n = 1) during the EA treatment. Nonetheless, these events were mild and transient and were resolved before discharge. Five patients took acetaminophen as a rescue medication during the study period (once in four patients and three times in one patient).

Discussion

In this pilot study, we, pain physicians and KMDs, completed a multicenter study according to the unique three steps: (1) all participants were enrolled by a pain physician (JYM), (2) the EA treatments were conducted in a different hospital by two KMDs, and (3) evaluation was carried out independently in the first hospital. EA treatment with a regimen of twice a week for 1 month showed substantial pain reduction (46.7%) in patients with intractable chronic NeP. The incidence of “severe” burning, electric shock-like pain, and pain with slight pressure seemed to decrease during the EA treatment period. The affective dimensions in SF-MPQ and the pain interference, including mood, relations with other people, and enjoyment of life in the BPI-SF, were likely improved at 4 and 8 weeks. Two-third of the patients (n = 13/22) responded that their pain was “much or somewhat improved.” Although patients had to visit a different hospital 12 times, the compliance rate of the EA treatment was high as 97.3%, accompanied by 84.2% satisfaction with the integrative approach. Three patients were excluded due to the protocol violence, but no participant withdrew voluntarily from the study. Therefore, 12 sessions of EA treatment for 8 weeks could be a feasible and safe protocol for managing chronic NeP.

In previous studies, more number of acupuncture sessions seemed to lead better clinical outcomes for managing of NeP.^16,29,30. However, there has been a lack of an adequate number or interval of EA treatments. In this study, EA treatment twice a week for the first month reduced pain intensity by 46.7% from the baseline (p < 0.001). Otherwise, EA treatment once a week for the following month decreased pain intensity by only 12.1% (p = 0.009), which was too minimal in the NRS pain scores (from 6.0 at baseline to 5.3 at the final visit) to reach clinical benefit.³¹ Possibly, some placebo effects would affect pain reduction during the first month. However, our results would support that the number of EA sessions is one of the crucial factors in obtaining favorable results in the management of NeP. Furthermore, in a previous study, EA treatment with a regimen of only once a week for 6 weeks failed to prove its effectiveness for managing NeP.³² Therefore, we suggest that the protocol of administering EA treatment at least twice a week is necessary to yield positive outcomes for the management of NeP for a larger confirmatory trial.

In this pilot study, among the various NeP symptoms, the incidence of severe electric shock-like pain was reduced from 53% of the participants to 26% at 8 weeks. In addition, the intensity of severe burning and pain with slight pressure seemed to decrease by the end of the 12 EA treatment sessions. The improvement of various symptoms in NeP may come from suggestions that EA acts on diverse NeP mechanisms. Animal studies have reported that EA procedure activates bioactive chemicals, such as opioids, serotonin, norepinephrine, and GABA.^12
–14,33 Then, they modulated the NeP pathways from peripheral to supraspinal levels, which are the targets of the conventional analgesics in the management of NeP. Besides, some animal studies have suggested that EA enhances the effects of NeP medications and lowers their dosages, followed by forestalling the side effects.^13,34,35 Future clinical trials focusing on a decrease in the use of analgesics may be a good chance to provide clinical evidence of the EA.

Affective disorders often accompany chronic NeP conditions and worsen their recovery. Numerous studies have reported the advantage of EA in the various aspects of QoL, including depression, mood, sleep disturbances, and others.^36,37 Similarly, we found that affective dimensions, such as depressive mood, relationship with other people, and overall QoL, improved after the 2-month EA treatment. EA might induce endogenous opioids in the anterior cingulate cortex, which could suppress N-methyl-D-aspartate receptor functions,^13,38 relieving pain-related affective disorders. A systematic review noted that EA might have an antidepressant effect by boosting serotonin and noradrenaline.³⁹ Furthermore, this antidepressive effect occurred separately from the reduction of pain.^13,40 Our results showed similar results with previous studies, which suggested that acupuncture is useful in relieving emotional comorbidities.^28,41 Based on our results, well-designed future studies, focusing on the EA treatment for managing insomnia, anxiety, and depression, are also warranted.

There are several flaws in this study. First, the major limitation in this pilot trial was the small sample size and the lack of a follow-up period, which could not generalize our results at the moment. We enrolled patients with painDETECT scores ≥19, indicating the existence of NeP strongly; however, the diversity in the diagnoses of NeP may impose restrictions to generalize our results as well. Second, although the pain reduction of 46.7% in our study is more significant than that observed in previous placebo-controlled trials of NeP and chronic intractable pain,^37,42 there was no control group to eliminate a possible placebo effect. Moreover, in this study, imposing an add-on design, EA treatment was given in addition to traditional therapies, which was a wide range of treatments. Although there was no change in conventional treatment during the study periods, the differences in therapy in each patient could be a bias to test the effectiveness of EA in patients with NeP. To overcome these limitations, we started a more extensive confirmatory study to prove EA as an effective therapy for managing NeP and affective disorders in patients with intractable peripheral NeP (KCT0003615).

Conclusions

These preliminary results suggest that EA might be a possible complementary option for reducing the intensity of NeP and enhancing affective dimensions in patients who are refractory to conventional NeP management. The protocol with 12 sessions of EA treatment for 8 weeks is a feasible way, which could be imposed for a large-scale clinical trial to evaluate the effectiveness of EA treatment. We look forward to the current pilot study being a cornerstone of future investigations to improve NeP and the associated affective illness.

Footnotes

Authors' Contributions

Study design: S.L., C.-S.L., H.-G.S., J.Y.M., J.K., S.H.L. Data collection: S.L., C.-S.L., J.Y.M., J.K., H.S. Statistical analysis: S.L., C.-S.L., J.Y.M. Data interpretation: S.H.L., C.-S.L., Y.Y., J.Y.M. Article preparation: S.L., C.-S.L., H.-G.S., J.Y.M. Literature search: S.L., Y.Y, J.Y.M. Funds collection: S.L., J.Y.M., S.L. All authors have read and approved the final version of the article for publishing.

Acknowledgments

The authors thank all participating patients, colleagues, and the staff of the institutions for their contributions in data collection during the study period.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No.: HI16C2365).

Supplementary Material

Supplementary Figure S1

References

Truini

. A review of neuropathic pain: From diagnostic tests to mechanisms. Pain Ther, 2017; 6(Suppl 1):5–9.

Bouhassira

, Lantéri-Minet

, Attal

, et al. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain, 2008; 136:380–387.

O van

Hecke

, Austin

, Khan

, et al. Neuropathic pain in the general population: A systematic review of epidemiological studies. Pain, 2014; 155:654–662.

Cohen

, Mao

. Neuropathic pain: Mechanisms and their clinical implications. BMJ, 2014; 348:f7656.

Davari

, Amani

, Khanijahani

, et al. Pregabalin and gabapentin in neuropathic pain management after spinal cord injury: A systematic review and meta-analysis. Korean J Pain, 2020; 33:3–12.

Rosenblum

, Marsch

, Joseph

, Portenoy

. Opioids and the treatment of chronic pain: Controversies, current status, and future directions. Exp Clin Psychopharmacol, 2008; 16:405–416.

Castañeda

, Lee

, Kim

, et al. Addressing opioid-related chemical coping in long-term opioid therapy for chronic noncancer pain: A multicenter, observational, cross-sectional study. J Clin Med, 2018; 14:354.

McNicol

, Midbari

, Eisenberg

. Opioids for neuropathic pain. Cochrane Database Syst Rev, 2013; 29:CD006146.

Vickers

, Cronin

, Maschino

, et al. Acupuncture trialists' collaboration. acupuncture for chronic pain: Individual patient data meta-analysis. Arch Intern Med, 2012; 172:1444–1453.

10.

Qaseem

, Wilt

, McLean

, et al. Noninvasive treatments for acute, subacute, and chronic low back pain: A clinical practice guideline from the American College of Physicians. Ann Intern Med, 2017; 166:514–539.

11.

Mendell

. Constructing and deconstructing the gate theory of pain. Pain, 2014; 155:210–216.

12.

Silva

, Silva

, Prado

. Analgesia induced by 2- or 100-Hz electroacupuncture in the rat tail-flick test depends on the activation of different descending pain inhibitory mechanisms. J Pain, 2011; 12:51–60.

13.

Zhang

, Lao

, Ren

, Berman

. Mechanisms of acupuncture-electroacupuncture on persistent pain. Anesthesiology, 2014; 120:482–503.

14.

Han

. Acupuncture and endorphins. Neurosci Lett, 2004; 361:258–261.

15.

Goldman

, Chen

, Fujita

, et al. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat Neurosci. 2010; 13:883–888.

16.

Takano

, Chen

, Luo

, et al. Traditional acupuncture triggers a local increase in adenosine in human subjects. J Pain, 2012; 13:1215–1223.

17.

, Wang

, Cui

, et al. Acupuncture for neuropathic pain in adults. Cochrane Database Syst Rev, 2017; 12:CD012057.

18.

Tick

, Nielsen

, Pelletier

, et al. Evidence-based nonpharmacologic strategies for comprehensive pain care: The Consortium Pain Task Force White Paper. Explore (NY). 2018; 14:177–211.

19.

Wang

, Yang

, Wang

, Li

. Acupoint specificity on colorectal hypersensitivity alleviated by acupuncture and the correlation with the brain-gut axis. Neurochem Res, 2015; 40:1–9.

20.

Han

, Wang

, Shi

, et al. Acupuncture combined with methylcobalamin for the treatment of chemotherapy-induced peripheral neuropathy in patients with multiple myeloma. BMC Cancer, 2017; 17:40.

21.

Sung

, Choi

, Jeong

, et al. Korean version of the painDETECT questionnaire: A study for cultural adaptation and validation. Pain Pract, 2017; 17:494–504.

22.

MacPherson

, Altman

, Hammerschlag

, et al.; STRICTA Revision Group. Revised standards for reporting interventions in clinical trials of acupuncture (STRICTA): Extending the CONSORT statement. J Evid Based Med, 2010; 3:140–155.

23.

Filshie

, White

, Cummings

. Medical Acupuncture: A Western Scientific Approach, 2nd ed. Amsterdam, Netherlands: Elsevier, 2016.

24.

Park

, Marcela Castañeda

, Jae-Kyu

Choi

, et al. Psychometric evaluation of the Korean versions of the McGill Pain Questionnaire—Short Form (MGPQ-SF) and Neuropathic Pain Scale (NPS) in neuropathic pain patients. Int J Pain, 2017; 8:1–15.

25.

Yun

, Mendoza

, Heo

, et al. Development of a cancer pain assessment tool in Korea: A validation study of a Korean version of the brief pain inventory. Oncology, 2004; 66:439–444.

26.

Kind

, Dolan

, Gudex

, Williams

. Variations in population health status: Results from a United Kingdom national questionnaire survey. BMJ, 1998; 316:736–741.

27.

Kim

, Cho

, Uhm

, et al. Cross-cultural adaptation and validation of the Korean version of the EQ-5D in patients with rheumatic diseases. Qual Life Res, 2005; 14:1401–1406.

28.

Lee

, Park

, Moon

, et al. An exploratory study on the effectiveness of “Calmare therapy” in patients with cancer-related neuropathic pain: A pilot study. Eur J Oncol Nurs, 2016; 32:1–7.

29.

Manheimer

, Cheng

, Linde

, et al. Acupuncture for peripheral joint osteoarthritis. Cochrane Database Syst Rev, 2010; 20:CD001977.

30.

MacPherson

, Maschino

, Lewith

, et al. Characteristics of acupuncture treatment associated with outcome: An individual patient meta-analysis of 17,922 patients with chronic pain in randomised controlled trials. PLoS One, 2013; 8:e77438.

31.

Farrar

, Young

Jr , LaMoreaux

, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain, 2001; 94:149–158.

32.

Penza

, Bricchi

, Scola

, et al. Electroacupuncture is not effective in chronic painful neuropathies. Pain Med, 2011; 12:1819–1823.

33.

Dai

, Kondo

, Fukuoka

, et al. The effect of electroacupuncture on pain behaviors and noxious stimulus-evoked Fos expression in a rat model of neuropathic pain. J Pain, 2001; 2:151–159.

34.

Zhang

, Lao

, Wang

, et al. Involvement of opioid receptors in electroacupuncture-produced anti-hyperalgesia in rats with peripheral inflammation. Brain Res, 2004; 1020:12–17.

35.

, Mao-Ying

, Liu

, et al. Synergistic anti-hyperalgesia of electroacupuncture and low dose of celecoxib in monoarthritic rats: Involvement of the cyclooxygenase activity in the spinal cord. Brain Res Bull, 2008; 77:98–104.

36.

Quispe-Cabanillas

, Damasceno

, von Glehn

, et al. Impact of electroacupuncture on QoL for patients with relapsing-remitting multiple sclerosis under treatment with immunomodulators: A randomized study. BMC Complement Altern Med, 2012; 12:209.

37.

Shin

, Lee

, et al. Electroacupuncture for painful diabetic peripheral neuropathy: A multicenter, randomized, assessor-blinded, controlled trial. Diabetes Care, 2018; 41:e141–e142.

38.

Martin

, Nie

, Siggins

. mu-Opioid receptors modulate NMDA receptor-mediated responses in nucleus accumbens neurons. J Neurosci. 1997; 17:11–22.

39.

Smith

, Hay

, Macpherson

. Acupuncture for depression. Cochrane Database Syst Rev, 2010; 20:CD004046.

40.

LaGraize

, Borzan

, Peng

, Fuchs

. Selective regulation of pain affect following activation of the opioid anterior cingulate cortex system. Exp Neurol, 2006; 197:22–30.

41.

Yin

, Gou

, Xu

, et al. Efficacy and safety of acupuncture treatment on primary insomnia: A randomized controlled trial. Sleep Med, 2017; 37:193–200.

42.

Williamson

, Sagman

, Bruins

, et al. Antidepressants in the treatment for chronic low back pain: Questioning the validity of meta-analyses. Pain Pract, 2014; 14: E33–E41.

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