Acupuncture combined with medication for postherpetic neuralgia affecting the head and face:a randomized controlled trial

Zhai Chun-tao (翟春濤), Lü Yu-e (呂玉娥)

1 Acupuncture and Massage College, Shanxi University of Chinese Medicine, Jinzhong 030619, China

2 Shanxi Acupuncture Hospital, Taiyuan 030012, China

Abstract

Keywords: Acupuncture Therapy; Surrounding Needling; Acupuncture Medication Combined; Point, Xi (Cleft); Neuralgia,Postherpetic; Visual Analog Scale; Quality of Life

Herpes zoster (HZ) is an acute skin disease caused by varicella-zoster virus, affecting skin and nerves. Elderly people and those with poor immune function are more likely to be affected. Its incidence is estimated to be 1.2‰-4.8‰[1], and 9.0%-34.0% of HZ patients will suffer from subsequent postherpetic neuralgia (PHN)[1], whose onset risk is associated with age, gender and a history of HZ virus infection. There are around 4 million PHN patients in China, whose quality of life (QOL) has been negatively influenced. To date, antiviral and neurotrophic drugs are mainly used to manage PHN in Western medicine, as these medications can somewhat reduce pain and other discomforts, though the total effective rate was only 60.0%-75.0%[2]. Xi-Cleft points are where qi and blood gather in the deep layer of the body, acting to regulate the meridian qi and modulate the function of Zang-fu organs. They are often used to treat acute medical conditions originating from Zang-fu organs and meridian system.Zhen Jiu Jia Yi Jing(A-B Classic of Acupuncture and Moxibustion) has already clearly defined the names and locations of Xi-Cleft points,putting forward that Xi-Cleft points from yang meridians are usually used for relieving pain. This trial was to observe the clinical efficacy of needling Xi-Cleft points of yang meridians plus topical surrounding needling and pregabalin in treating PHN affecting the head and face and its effect on QOL. The report is as follows.

1 Clinical Materials

1.1 Diagnostic criteria

Diagnostic criteria in Western medicine referred the Consensus of Chinese Experts on Diagnosis and Treatment of Postherpetic Neuralgia[3]. Diagnostic criteria in traditional Chinese medicine (TCM) referred that for She Chuan Chuang in theCriteria of Diagnosis and Therapeutic Effects of Diseases and Syndromes in Traditional Chinese Medicine[4].

1.2 Inclusion criteria

Conformed to the above diagnostic criteria; persistent pain for over 1 month following HZ; visual analog scale(VAS) score ≥6 points; willing to participate in the trial and having signed the informed consent form.

1.3 Exclusion criteria

Received other treatment within the past 1 week but didn’t respond to it well; special type of HZ, e.g.generalized HZ, severe facial HZ, meningeal HZ, and so on;comorbidities such as tumors, hematologic diseases or connective tissue diseases; pregnant or breast-feeding women.

1.4 Elimination and dropout criteria

Failed to rigorously follow the treatment protocol in the trial; serious adverse events or complications; those who withdrew or missed the follow-up.

1.5 Statistical methods

Statistical analysis was performed using SPSS 21.0.Measurement data were expressed as mean ± standard deviation (±s). Two independent samplet-test was applied for between-group comparison of the measurement data conforming to normal distribution and homogeneity of variance; otherwise, it would be examined using non-parametric Mann-WhitneyUtest.Enumeration data were presented as rate. Those eligible data were analyzed by Person’s Chi-square, while those were processed using continuity correction of Pearson's Chi-square test or Fisher’s exact probability test.Between-group comparison of ranked data was performed by non-parametric rank sum test. Statistical significance was recognized whenP<0.05.

1.6 General data

A total of 80 patients who visited Shanxi Acupuncture Hospital between March 2015 and March 2017 for PHN affecting the head and face were included. All the patients were randomized into 2 groups according to their visiting number, and the corresponding grouping plan for each number was hidden in an envelope, either the acupuncture-medication group or the Western medication group, with 40 cases in each group.There were no dropout cases during intervention. The between-group comparisons of age, gender and disease duration showed statistical insignificance (allP>0.05).The details are shown in Table 1.

This trial had been approved by Ethics Committee of Shanxi Acupuncture Hospital (Approval No. 2015LC019).

Table 1. Comparison of general data

2 Treatment Methods

All the patients were offered antiviral and neurotrophic treatment as well as conventional symptomatic treatment for other primary diseases.

2.1 Western medication group

Orally took pregabalin capsules (State Food and Drug Administration Approval No. H20130073, 75 mg/capsule,Chongqing Succeway Pharmaceutical Co., Ltd., China),75 mg each time, twice a day. The dosage could increase to 150 mg each time and twice a day within 1 week based on the efficacy and tolerance of the patients. This treatment lasted for 5 weeks.

2.2 Acupuncture-medication group

Acupuncture treatment was conducted in addition to the abovementioned pharmaceutical treatment.

2.2.1 Surrounding needling at the HZ area

Method: First, make sure that there was no skin damage in the topical area before standard sterilization.Disposable filiform needles of 0.30 mm in diameter and 40 mm in length were used to puncture at 5 mm outside the border of the painful zone with the needle tips towards the center forming a 15° angle with skin, with small-amplitude lifting-thrusting and twirling reducing manipulations. The distance between needles and needling depth were dependent on the extent of pain.Generally, the distance was 10-25 mm and the depth was 7-12 mm.

2.2.2 Needling Xi-Cleft points

Acupoints: Bilateral Waiqiu (GB 36), Yangjiao (GB 35),Wenliu (LI 7), Liangqiu (ST 34), Yanglao (SI 6), Jinmen(BL 63), Fuyang (BL 59) and Huizong (TE 7).

Operation: Xi-Cleft points of yang meridians were chosen according to the route of each yang meridian and the location of HZ on the head and face. The acupoints were located based on theNomenclature and Location of Acupuncture Points(GB/T12346-2006). Disposable filiform needles of 0.30 in diameter and 50 mm in length were used for perpendicular puncture and liftingthrusting and twirling reducing manipulations were performed after needling qi sensation was achieved.

The needles were retained for 30 min, during which manipulations were performed once. The treatment was offered once every other day, for a total of 5 weeks.

3 Observation of Therapeutic Efficacy

3.1 Observation items

3.1.1 Pain score

Before and after treatment, pain intensity was measured using visual analog scale (VAS)[4], in which patients were asked to mark on a scale of 10 cm in length to express the intensity of pain and the mark was taken as the score. 0 suggested no pain; 1-3 points suggested mild pain; 4-6 points, moderate pain; 7-10 points,intensive pain.

Pain reduction index was calculated using VAS score.Pain reduction index = (Pre-treatment VAS score -Post-treatment VAS score) ÷ Pre-treatment VAS score ×100%.

3.1.2 QOL score

Before and after treatment, diet, sleep, state of mind,interests in life and daily activities were scored in the patients using a 10-point scale, with 10 standing for the worst and 0 for the best[5].

3.2 Criteria for therapeutic efficacy

Therapeutic efficacy was evaluated according to the

Criteria of Diagnosis and Therapeutic Effects of Diseases and Syndromes in Traditional Chinese Medicine[4].

Recovery: Pain was gone completely and pain reduction index was 100.0%.

Markedly effective: Pain was reduced notably and pain reduction index was ≥80.0% but <100.0%, not affecting daily activities and life.

Effective: Pain showed certain improvement and pain reduction index was ≥30.0% but <80.0%, casting some influence on daily activities and life.

Invalid: Pain showed no improvement or became worse.

3.3 Results

3.3.1 Comparison of clinical efficacy

After treatment, the total effective rate was 67.5% in the Western medication group, versus 92.5% in the acupuncture-medication group, and the between-group difference was statistically significant (χ2=7.812,P=0.005),(Table 2).

3.3.2 Comparison of VAS score

There was no significant difference in the VAS score between the two groups prior to treatment (P>0.05);after treatment, VAS score declined in each group, and the intra-group differences were statistically significant(bothP<0.01), and the score was lower in the acupuncture-medication group than in the Western medication group, presenting with statistical significance(P<0.01), (Table 3).

3.3.3 Comparison of QOL score

There was no significant difference in the QOL score between the two groups prior to treatment (P>0.05);after treatment, QOL score decreased in each group, and the intra-group differences were statistically significant(bothP<0.01), and the score was lower in the acupuncture-medication group than in the Western medication group, presenting with statistical significance(P<0.01), (Table 4).

Table 2. Comparison of clinical efficacy between the two groups (case)

Table 3. Comparison of VAS score before and after treatment ( ±s, point)

Table 3. Comparison of VAS score before and after treatment ( ±s, point)

Group n Pre-treatment Post-treatment t-value P-value Acupuncture-medication 40 6.45±1.31 1.06±0.821)2) 22.057 0.001 Western medication 40 6.32±1.44 3.22±1.011) 11.147 0.001 t-value -0.422 10.501 P-value 0.674 0.001

Table 4. Comparison of QOL score before and after treatment ( x ±s, point)

4 Discussion

The varicella-zoster virus that causes HZ usually lurks in the dorsal root ganglion of spinal nerve. It can be reactivated when immune function of the body declines,and produce clusters of herpes along the corresponding sensory nerve distribution segments, causing inflammation and necrosis of the involved nerves,accompanied by intensive neuropathic pain in the acute stage or after the skin lesions subside. Research found that over 90.0% of HZ patients had typical neuralgia, and even severe neuralgia in the acute stage; 9.0%-13.0% of HZ patients suffered from HPN, which gravely affected QOL of the patients[3]. The pathogenesis of PHN is not completely clear at present, but it may be related to inflammatory reactions[6], peripheral and central nerve injuries[7-8], nerve fiber injuries[9], etc. To date, there is no cure for HPN yet. Western medicine manages it mainly by anti-virus, nourishing nerves, reducing inflammation and relieving pain. Although these treatments can relieve pain and other discomforts to a certain extent,their effective rate is not high and may bring on obvious adverse reactions[10].

Surrounding needling at the painful area of HZ can notably quicken the onset of effect and the healing of skin lesions, and lower the incidence of subsequent neuralgia[11-12]. Zhao XJ,et al[13]found that modified superficial electroacupuncture combined with surrounding needling was effective in treating HZ, and this method showed several merits including using less acupoints, less treatment times and avoiding potential medical risks. Clinical studies also demonstrated that acupuncture not only can improve pain in PHN[14-17], but also down-regulate cytokine levels relevant to pain [such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β and IL-10] and pain factors [such as 5-hydroxytryptamine(5-HT) and substance P (SP)][18]. Therefore, acupuncture has been widely used in the clinical treatment of HZ[19].

HZ equals to Chan Yao Huo Long or She Chuan Chuang in TCM. TCM holds that depression and gloominess, liver stagnation transforming into fire, internal damp-heat and exogenous damp can all lead to HZ, so it should be treated based on the causing factors and diseased location via syndrome differentiation. HZ that occurs on the head and face can be treated using Xi-Cleft points of yang meridians. Here, Xi-Cleft shares the same meaning with another Chinese character ‘Xi’, which means space.Xi-Cleft points are where meridian qi and blood gather in the deep layer of the body. Each of the twelve ordinary meridians, Yin Heel Vessel, Yang Heel Vessel, Yin Link Vessel and Yang Link Vessel has a Xi-Cleft point. Most of the 16 Xi-Cleft points are located below the elbow or knee joints. In clinical practice, these points are usually used to treat acute medical conditions that affect the route of its affiliated meridian or corresponding Zang-fu organs. It’s mainly concluded that the Xi-Cleft points from yang meridians are often used for acute pain and those from yin meridians are usually for acute bloodrelated conditions. The six yang meridians of hand and foot all go up to the head and face. Acupuncture at Xi-Cleft points from yang meridians can not only regulate the meridian qi, but also improve qi and blood circulation of the organs, so as to promote blood flow, remove blood stasis and dredge meridian qi. Research found that acupuncture at Xi-Cleft points can improve nerve excitability and plasticity, activate the injured cells for self-repair, boost blood circulation, improve microcirculation and rebuild blood oxygen supply[20].Therefore, in this study, besides oral administration of pregabalin, acupuncture at Xi-Cleft points of yang meridian and topical surrounding needling were added in the acupuncture-medication group. The results demonstrated that this joint treatment method produced more significant clinical efficacy than oral pregabalin alone, together with better effects in improving VAS and QOL scores, suggesting that this treatment scheme can not only relieve the pain of the patients, but also significantly improve the QOL, thus worthy of clinical application and promotion.

Conflict of Interest

The authors declare that there is no potential conflict of interest in this article.

Acknowledgments

This work was supported by Soft Science Project of Shanxi Province ( 山西省軟科學研究項目, No.2016041033-3); Innovation Team Project of Shanxi University of Chinese Medicine (山西中醫(yī)藥大學創(chuàng)新團隊項目, No. 2019TD-003).

Statement of Informed Consent

This trial was approved by the Ethics Committee of Shanxi Acupuncture Hospital (Approval No. 2015LC019).Informed consent was obtained from all individual participants.

Received: 16 May 2020/Accepted: 25 September 2020