Visual abstract

Introduction

Pain is defined as an unpleasant physiological and emotional sensation that is associated with actual or potential tissue damage [1]. Pain threshold i.e., the amount of stimulus required to cause pain is more dependent on physiological factors, whilst pain tolerance i.e., the maximum intensity of pain someone can endure, is more dependent on psychological factors [1]. By any measure, pain is an enormous global health problem. Worldwide, it has been estimated that 20%–25% of adults suffer from persistent pain, and 10% are newly diagnosed with chronic pain each year [2]. Numerous modulatory systems have been identified that control pain through complex processes including descending antinociceptive pathway [3], endogenous pain inhibitory system, diffuse noxious inhibitory control, gate control, the descending modulatory system, and neuromodulators [4]. In 2016, in an overview for anesthesiologists, it was reported that many countries are facing a surge in the prescribing of opioids, which has prompted the term “opioid epidemic” [5]. In a review of the risk of opioid abuse in patients with cancer, it was reported that approximately 1 in 20 people taking opioid painkillers may become addicted [6]. Therefore, it is vital for researchers and clinicians to explore whether nonpharmacological approaches to managing pain can be effective. This may relieve reliance on opioid analgesics.

Acupuncture can be an effective tool to modulate pain, it is one of the most popular modalities of complementary and alternative medicine, and is a widely accepted modality for the treatment of a variety of pain conditions [7]. Using a commonly used acupoint for treating pain-related conditions, acupoint LI 4 (Hegu), the effect of acupuncture on pressure pain threshold (PPT) has been studied and has shown “both manipulation and site of needling contributed significantly to the elevation of PPT following acupuncture” [8].

In this current study, another acupoint used for treating pain-related conditions, Small Intestine 3 (SI3 -Houxi), was used to assess whether acupuncture could modulate PPT [9]. Regional PPTs were measured using a commonly employed technique (widely used in physiotherapy research studies) called pressure algometry [10].

Acupuncture uses various manual manipulation needling techniques with therapeutic benefits varying dependent on the specific method and manipulation used [11,12]. A study reported that repeated needling manipulation led to more significant local microcirculatory changes, which were linked to analgesic effects at the targeted sites [13].

In this current study, the effect of 2 different acupuncture techniques applied to SI3 was studied in healthy participants to determine the effects on regional PPT.

Material and Methods

The CONSORT checklist [14] was referred to when reporting this study.

1. Design

This study was a prospective cross-over design with repeat measures. The study involved 3 different interventions: (1) needling SI3 with manipulation (SI3m+); (2) needling SI3 without manipulation (SI3m−); and (3) sham laser (SL). The researcher recording the PPT scores and the statistician analyzing the results were blind to the interventions administered.

2. Sample size calculation

The sample size for the study was calculated using GPower Version 3.1.9.2 (a free downloaded software). The significance level was fixed at 0.05, and the power of the study was ≥ 0.8 and ≤ 0.95 (by convention). For this cross-over trial, it had been determined prospectively that α = 0.05, 1-β = 0.80, the test would be one tailed according to the previous studies [7,15], and the effect size was anticipated to be 0.5. Thus, 27 participants were required for the study to show meaningful results. To compensate for a potential 20% dropout, the intension was to enroll 33 participants in the study.

3. Study setting

The study site was the University of Technology Sydney, and the setting was the Chinese medicine clinic. The clinic is a teaching facility where students of Chinese medicine treat patients under supervision and where academic research may be conducted. The participants laid supine on a couch and their line of vision to the treatment site on their hand was obstructed by a curtain.

4. Participants

Recruitment strategies aimed to achieve adequate participant enrolment to reach the target sample size. (Applicants were screened and recruited until the target sample size of 32 participants was reached. Since 31 participants’ data had been collected completely, the 33^rd. participant was not recruited). The enrollment period was over 4 months. All participants had signed the informed consent forms and acknowledged that they would receive 3 different acupuncture interventions in different sequences.

All potential healthy participants matching the eligible criteria had a face-to-face screening interview, which included a trial entry assessment and health evaluation. Participants eligible for the trial complied with all of the following inclusion requirements at randomization: (1) healthy, pain-free volunteers (regardless of ethnic background); (2) aged 18–70 years (both male and female participants); (3) right-handedness; (4) no medical history of chronic musculoskeletal disorder; (5) no diagnosis of pain caused by any diseases in the 7 days before study entry; (6) nonsmokers; (7) acupuncture practitioners and students of acupuncture were not excluded; (8) willingness to give written informed consent and willingness to participate and comply with the study requirements.

Participants matching any of the following criteria were excluded from the study: (1) depression or sleep disorders, complications of severe systemic diseases, such as cardio or cerebrovascular diseases, diabetes, kidney diseases, central or peripheral nervous system or digestive system diseases; (2) regular use of analgesic or other drugs (that may dampen pain perception); (3) hemophilia and use of anticoagulant medication (that may interfere with blood clotting); (4) chronic consumers of sedatives, especially benzodiazepine or antidepressants (inhibiting the reuptake of serotonin, were not enrolled in the study for the possible interference of the drugs on acupuncture action mechanisms); (5) women who were pregnant or menstruating; (6) alcohol abuse and/or drug abuse; (7) people highly dependent on medical care; (8) people with a cognitive impairment, an intellectual disability or a mental illness; (9) needle phobia; (10) allergy to metal; (11) participants who had received any type of acupuncture, massage, cupping, guasha or physio intervention in the 7 days before study entry; or (12) enrolled in other investigational studies.

5. Protocol

The current study was a randomized, three-arm, and cross-over experiment. In this cross-over study, a random sequencing of the 3 interventions for each participant was achieved using an envelope method that was also stratified by gender. The assessor generated the random number from the website RANDOM.ORG [16]. The researcher obtaining the PPT scores, and the statistician analyzing the data were blind to the intervention administered.

Since this study aimed to investigate a single acupuncture point, SI3, instead of different therapies for a certain condition, an active control was unnecessary. Although the first description of the location of SI3 was in the Ling Shu as a site on the surface of the body [17], the Yellow Emperor’s Classic of Medicine also recorded the “needling depth in acupuncture” [18], indicating the acupoint is a 3-dimensional structure. In addition, the complicated network of channels and collaterals, which comprise 12 main channels, luo collaterals, small collaterals, superficial collaterals, 12 divergent channels, the 15 divergent collaterals, and dermatomes of the channels [19], means that the choice of a nonacupoint or the use of minimally inserted acupuncture as a placebo comparator could result in confounding the study outcome. Therefore, the sham laser control was selected as a suitable control.

According to traditional Chinese acupuncture, needle manipulation techniques should be appropriate for treating pain syndromes [20]. Thus, the acupuncture point SI3 with either standardized manual needle manipulation or without manual needle manipulation were selected as a comparator intervention.

Eligible individuals were randomly, equally allocated into 3 intervention groups with 6 sequences; each group received the 3 interventions in different sequences. A qualified acupuncturist with over 35 years of clinical practice administered the acupuncture interventions. The 3 intervention groups were: “with manipulation” (SI3m+), “without manipulation” (SI3m−), and “sham laser” (SL). The 3 interventions were renamed for the individual session recording sheets (rose, tulip and daisy) so that only the acupuncturist administering the interventions knew the actual intervention the participant received. This allowed blinding of the researcher taking the PPT measurements and the person analyzing the data at the completion of the study. Study participants knew that a laser intervention was to be administered but did not know it was the sham laser. The outcome assessor was blinded after assignment to interventions. Due to the nature of the acupuncture intervention, it was difficult to blind the acupuncturist. The follow-up period was 1 month after the experiment via the telephone.

A single-use, stainless steel, sterile filiform with guide tube 0.22 × 25 mm (C&G; Helio Supply Co. Pty Ltd.) needle was inserted at the acupuncture point SI3 in the right hand. The acupuncturist inserted the needle perpendicularly (90°) into the skin and to a depth of approximately 7.5–12.5 mm [20–23].

For the SI3m+ intervention, once the needle was inserted to the appropriate level, the needle was manipulated to obtain deqi. The needle was manipulated by holding the needle and rotating between the thumb and index finger through a 540°–720° angle in a bidirectional manner (neutral supplementation and drainage) with a speed of 2–4Hz for 5 seconds or to patient tolerance. This was applied just after needle insertion and every 3-minutes for the study period. The needle was retained for 21 minutes withdrawn and the site pressed with a cotton ball for 1 minute.

For the SI3m− intervention, following insertion of the needle to the appropriate depth, there was no attempt to obtain deqi. Following needle insertion and at every 3 minutes, the acupuncturist rested the hand in the same position, as in the SI3m+ intervention, and lightly moved his fingers next to the acupuncture needle to mimic movements that would accompany needle manipulation. This is referred to as “simulated manipulation.” The needle was retained for 21 minutes. The control intervention was inactive laser therapy which was applied with an inactive laser probe resting lightly on the skin SI3 on the right side. The low-level laser unit (Microlase, Melbourne, Australia) had the laser diode (gallium aluminum arsenide) removed. A sham laser must have either light or sound to indicate functionality to the participant, and there was a warning about the “harmfulness” of the laser to the eyes. The participants knew they were receiving a laser intervention but did not know it was a sham laser. The laser probe rested lightly on the skin above SI3 for 20 seconds every 3 minutes. The unit emitted a regular audible beep during each 3-minute period of “stimulation.” Each session was 21 minutes in duration. Eligible participants were randomly allocated into 6 sequences with a 1:1:1:1:1:1 ratio (Figure 1). PPT scores were obtained immediately before and after each treatment. Each participant received 3 different interventions, and the washout period between interventions was at least 1 week. The schedule of outcome measures, data administration and collection time points are presented in Table 1.

6. PPT measurements

With increasing attention to pain, the pain threshold has become an important part of pain-related studies. PPT at defined sites were measured as kilograms of force. PPT was measured at 10 regional acupoint locations which were either midline or on both sides of the body: GV 4 (Mingmen), GV 14 (Dazhui), SI 11R (Tianzong), SI 11L, GB 21R (Jianjing), GB 21L, HT 7R (Shenmen), HT 7L, BL 60R (Kunlun), and BL 60L by the trained assessor. The pain threshold scores were measured at 10 acupoints on the traditional acupuncture channels that have a theoretical relationship with the Small Intestine channel such as the Governor Vessel (GV 14, GV 4), Bladder Channel (BL 60), Heart Channel (HT 7), and the Small Intestine Channel (SI 11). For example, the SI3 point is the confluence point (ba mai jiao hui xue) for the Governing Vessel, the Bladder Channel is the partner channel from a 6-channel (liu jing) perspective, the Heart Channel is its partner channel from a 5-phase perspective (zang fu- biao li), the Small Intestine 11 is on the same channel as SI3, while the Gall Bladder Channel (GB 21) has no specific relationship to the Small Intestine Channel. The locations of the acupuncture points follow the World Health Organization point location text [24]. These were recorded once at each acupoint for each time point. Three measurements at each site were taken prior to the administration of each intervention, and then 3 measurements were obtained following the intervention. The mean was calculated for each of the 3 measurements, both pre and postintervention. There was only 1 algometer (WAGNER, FPK 20) used to reduce the risk of requiring recalibration. The assessor was trained and experienced in using the algometer. To minimize the influence of random errors, the mean of 3 PPT measurements (both pre and post measurements) were obtained during the PPT tests.

7. Statistical analysis

To analyze the quantitative data, it was initially entered into EXCEL and IBM SPSS Statistics 26 for Windows Version 10. For each participant and intervention session, all post PPT scores were reported as a percentage of the mean preintervention value, the mean of the 3 PPT measurements obtained prior to administration of the intervention. This was calculated using the following formula [25]:

PPT value as % of preintervention mean=PPT (Kgcm2) for this site×100%mean preintervention PPT (Kgcm2)

This data transformation was applied in view of the range of baseline PPT measurements encountered both between participants and with respect to the same participant across the 10 regional measurement sites. Extensive checking of the appropriateness of both the transformation and the model tested in the General Linear Model was undertaken. Further, it has been reported in a related study that baseline PPT is not a useful predictor of the percentage change following an active intervention [26]. Comparisons were made both within each intervention across all 10 PPT measurement sites, and between the 3 interventions for each individual PPT measurement site. In addition, a Tukey post-hoc test for multiple comparisons was conducted to identify statistical differences between the 3 intervention and measurement sites.

Results

Between November 2018 and March 2019, 32 healthy volunteers were enrolled in the study (Figure 2). One participant discontinued treatment prematurely due to scheduling difficulties. The characteristics of 31 participants are presented in Table 2. The mean age was 41.9 years, with a mean body mass index of 23.3 kg/m².

1. Within intervention comparisons en bloc-postintervention changes in mean % PPT

The 95% confidence intervals and adjusted significance levels are shown in Table 3 for the 3 interventions en bloc (without differentiating each measurement site). Statistically significant increases in mean % PPT were observed for 2 of the 3 interventions (p < 0.0001 for both SI3m- and SI3m+ needling interventions), while no significant increase was observed for the sham laser intervention (p > 0.1; Table 3 and Figure 3). For the 3 interventions, mean PPT changes ranged from 23.7% (SI3m+) to 0.2% (SL).

2. Between intervention comparisons en bloc-postintervention changes in mean % PPT

Whilst it had been shown there were statistically significant PPT increases obtained for the en bloc analysis for the within intervention comparison, it was also noted that the statistically significant effects were for the intervention and regional sites that were responsible for the change (p < 0.001). In addition, because the 2 acupuncture interventions significantly increased the mean % PPT from preintervention scores (baseline), it was necessary to determine whether there was a difference between each intervention for the mean % PPT changes observed. The differences between intervention (en bloc) and significance levels following post-hoc analysis are shown in Table 4. It was determined that the SI3m+ intervention produced statistically significantly greater changes in mean % PPT than the SI3m− intervention, and that both needling interventions (SI3m+ and SI3m−) produced significantly greater mean % PPT increases than the sham laser control.

3. Within intervention comparisons by site postintervention changes in mean % PPT from baseline

Significant increases in mean % PPT from baseline were observed at all 10 measurement sites following both the needling interventions of SI3m− and SI3m+ but, not for any of the 10 sites for the SL control intervention (Table 5). The range of scores observed for the SI3m+ intervention was from 15.5% (HT7^R) to 32.6% (SI11^L). With respect to the SI3m+ interventions at the 10 regional PPT measurement sites, statistically significant mean % PPT increases were observed at all 10 sites: HT7^R 15.5%, SI11^R 24.5%, GB21^R 20.3%, GV14 24.4%, GB21^L 20.2%, SI11^L 32.6%, GV4 31.6%, HT7^L 22.6%, BL60^L 22.7% and BL60^R 22.7% (p < 0.0001 in all cases).

The mean % PPT at the measurement site GV4 following the SI3m+ intervention was the second largest increase observed, which was 31.6%, and very similar to the score for SI11^L.

The SI3m− intervention produced 10 significant means % PPT increases that ranged from 6.0% (HT7^R) to 24.5% (GV4). The increases from baseline for the SI3m− intervention at the 10 measurement sites were: 6.0% at site HT7^R (p < 0.05), 13.6% at site SI11^R (p < 0.0001), 10.7% at site GB21^R (p < 0.0001), 17.4% at site GV14 (p < 0.0001), 17.1% at site GB21^L (p < 0.0001), 22.5% at site SI11^L (p < 0.0001), 24.5% at site GV4 (p < 0.0001), 16.5% at site HT7^L (p < 0.0001), 15.2% at site BL60^L (p < 0.0001), and 17.9% at site BL60^R (p < 0.0001).

In contrast, no statistically significant changes from the preintervention mean % PPT were observed following the sham laser intervention at any of the 10 PPT measurement sites, with mean % changes ranging from −1.2 to 3.3.

4. Between intervention comparisons by 10 regional sites

The between-comparison changes at 10 different regional measurement sites are shown for all 3 interventions in Table 6. The postintervention changes in regional PPT were statistically significantly greater for SI3m+ than for sham laser intervention at all 10 sites (p ≤ 0.001). For the SI3m− intervention, changes were statistically significantly greater than SL at 9 sites (p < 0.05), the exception being for the site HT7^R (p = 0.216). While the needling at SI3m+ produced higher scores at all 10 regional sites compared to those following SI3m− it was only statistically significant at only 1 measurement site - SI11^R (p = 0.038).

5. Adverse effects

There were no adverse effects reported during the experiment or in the follow-up period.

Discussion

This was the first prospective manual acupuncture PPT study using the SI3 acupoint. It was a randomized, double-blind, crossover, controlled study conducted on healthy participants. The research objectives were to examine the role of needling on PPT using the acupoint SI3, situated on the right hand, on increasing PPT at 10 regional sites (SI 11^R, SI 11^L, GV 4, GV 14, BL 60^R, BL 60^L, HT 7^R, HT 7^L, GB 21^R, GB 21^L) following 3 different interventions.

This study has shown the influence of acupuncture therapy on the pain threshold has shown that acupuncture to SI3 can increase the regional PPT. Acupuncture with needle manipulation appeared to increase PPT greater than intervention without manipulation but this was not statistically significant (with the exception of 1 site).

This study was limited in that it was not possible to blind the acupuncturist to the treatment. However, all important outcome measures were assessed independently, thus complying with the participant and assessor blinding. In addition, PPT as an outcome measure in this study, the stability, reliability, and validity of the algometer measurements may be of concern as the repeated pressure form PPT may potentially cause a change in the pain threshold. This has been addressed in previous studies where dynamic pressure algometry has been shown to be reliable in the evaluation of pain thresholds with high temporal and spatial resolution [27,28]. The algometer can be applied as a simple clinical bedside examination technique and as a quantitative measurement for research data collection. Furthermore, the following approaches have been adopted to reduce any potential errors in using the mechanical algometer: (1) the acupuncture clinic where the data was collected was a temperature-controlled environment; (2) prior to use, the algometer accuracy was verified with test weights; (3) prior to each measure, the algometer was returned to zero; and (4) the person using the algometer had been well-trained and had sufficient practice to attain consistent pressure loading.

The data for the PPT reliability suggests that agreement is generally high, being slightly lower for higher PPT values [29]. Research in 2015, published in a PhD thesis reviewed the available raw PPT data from several studies that supported the reliability and reproducibility of PPT in human experimental research and there were no substantial or noticeable effects of age or body mass index on regional PPT. However, his study result showed that data analysis on PPT should be completed separately by gender, and experimental design for PPT between participants should ensure a matched gender ratio across groups. Therefore, the data analyses for this study should only consider the intervention, the regional measurement site, and the gender due to the limited sample size. Moreover, the limited sample size only allowed the PPT data to be analyzed by interventions and regional sites, and gender was excluded as a variable [30].

The overall effects on PPT of 3 interventions (SI3m−, SI3m+ and SL) on the acupoint SI3 located on the right hand showed that acupuncture can significantly increase the PPT at all 10 selected regional sites. For acupuncture without manipulation, site GV4 resulted in the highest elevation of PPT, and site SI11^L had the second-highest PPT increase. On the contrary, for acupuncture with manipulation, site SI11^L resulted in the highest increase of PPT, and site GV4 had the second-highest elevation of PPT. Interestingly, the increase of PPT with acupuncture at site HT7^R was the lowest, which is the closest site to the needling area of SI3. A possible explanation is that acupuncture to the right of SI3 can elevate the human body’s PPT universally, especially at site GV4, and the contralateral site SI11^L, but it has less influence on the close area and homolateral body regional site.

In general, acupuncture to the right SI3 with manipulation can increase PPT significantly greater than acupuncture without manipulation (p < 0.001). However, when comparing the 10 measurement sites, only SI11R showed a statistically significant difference between SI3m− and SI3m+ (p < 0.05). It could be interpreted that acupuncture to SI3 with manipulation can enhance PPT compared to without manipulation, especially at the contralateral shoulder region.

The current research is unique when compared with previous studies of acupuncture. This was the first study concerning SI3 as a single acupoint. It is surprising to find that no RCTs or pain studies using acupuncture to treat pain used the SI3 acupoint as a single needling site because SI3 is a commonly used acupoint in many pain treatments. Moreover, the use of a sham laser acupuncture control intervention minimized the nonspecific effects of the study, such as time-tied effects. The choice of a noninvasive sham laser control also allowed a comparison between an invasive (SI3m−) and a noninvasive control technique (SL) at SI3.

Although traditional Chinese acupuncture theory is based on philosophical premises and considered controversial, many researchers have been trying to integrate it into the modern medical system. In particular, to determine where needles are applied, what effect they have, and how the effect is achieved. In the classical jingluo (Ch: channels and collaterals) theory, the channels and collaterals are the pathways through which blood and qi flow, and the points are the important nodes on the pathways. Only following the insertion of an acupuncture needle in the specific acupoint can the specific channel be stimulated, thereby having a therapeutic effect. However, modern biology has not discerned a reliable anatomical basis for the channel and acupoint theory. Since we do not know exactly what acupoints are, the therapeutic effect of an acupoint remains a question of dispute.

This current study also determined that an increased PPT was related to needle penetration. However, acupuncture with manipulation can increase PPT to a greater extent than acupuncture without manipulation. It appears that SI3 is not only a general pain relief site for needling but also a specific effective acupoint for pain in the area around GV4 (lower lumbar region) and contralateral SI11 (upper lateral thoracic region), which supports the jingluo (channel) theory of traditional acupuncture. Interestingly, participant 13 expressed verbally noticeable pain reduction when this site was pressed heavily. The primary indications for needling SI3 should be pain relief along the Small Intestine channel, Governor Vessel, and Bladder channel. The study results appear consistent with SI3 being the meeting point of GV (1 of the 8 extraordinary channels). However, confirmation is not possible unless more PPT measurement sites could be assessed in the same channel.

According to the innervation of the spinal nerves, only the spinal nerves exiting between cervical vertebra 7 and thoracic vertebra 2 (C8 and T1) are related to the location of SI3 on the hand. It appears that the effects of needling the acupuncture point Houxi (SI3) on PPT are not modulated by these spinal nerves because the PPT scores increased significantly across the body, not just for the measurement sites within the dermatomes of the 2 spinal nerves exiting at C8 and T1.

Acupuncture can be used as a nonpharmaceutical approach to treating pain [31]. Elevation of the pain threshold may be 1 mechanism underlying this effect. This study investigated SI3 as an important pain relief acupoint. The results indicated that SI3 can be utilized as a general acupoint to increase the PPT, which can reduce somatic pain across the body. However, the range of PPT scores increased at the regional sites across the human body. For example, because of the specific increased effect demonstrated at the GV4 PPT measurement site (located on the lumbar spine), lower back pain could be specifically indicated rather than general body pain. Furthermore, SI3 had a better effect on increasing PPT at the contralateral measurement site of SI11; therefore, SI3 may be specifically indicated for treating contralateral shoulder pain.

Despite the strengths and potential clinical benefits identified, some cautions are required when interpreting the conclusions drawn from the current study. Firstly, this study has a small sample size due to the limited time allocated for the study. As a result, the validity of some outcomes may be questioned as a small sample size could overestimate the results [32]. Moreover, the small number of participants in the study could not allow investigation of the gender difference for the PPT outcomes. Secondly, the generalization of the results may be limited because of the nature of it being a single center study. Thirdly, only 10 regional sites on the body were selected for PPT measurement. More sites should be chosen if the traditional meridian theory is to be confirmed. Additionally, because the study used healthy participants only, the findings cannot be extrapolated to a diseased population, especially those with chronic pain. Because of the large individual PPT differences observed, the acquired PPT data may display a high degree of dispersion. In this study, few people presented with very high pain thresholds that could produce bias (Figure 3). Setting a standard PPT range to screen participants may solve this issue. Another limitation relates to the sham laser placebo control. A deactivated laser device represents a suitable placebo intervention. However, placebo laser acupuncture does not mimic acupuncture, and it does not control for the nonspecific effects of needling. Consequently, it can only provide a partial answer to the question of efficacy. Furthermore, as the study was designed with a washout period of only 1 week between interventions, there is always the possibility of some carry-over effect, which cannot be ruled out completely. Finally, as the outcome measurement tool, PPT may not accurately detect a decrease in participants with a very low baseline PPT score [33]. There were a few people with very high pain thresholds, and this could also produce a confounding effect (Figure 3).

Whereas all the findings in this study were regarding SI3, more pain-related acupuncture points could be explored in the future based on the approach of this study. In particular, pain-relevant shu points in the 5-transport points system (Ch: Wu Shu) should be investigated. Kim et al [34] conducted an animal experiment to observe the changes in the expression of neurotransmitters upon the needle insertion to the sea points (Ch: he points), 1 of the 5 transport points. Future studies could explore the effect of needling shu points of 5 transport points in other 11 main acupuncture channels on the changes of PPT or functions of neurotransmitters. Since the study showed a significant increase in PPT in the intervention groups compared to the control group, it encourages researchers to replicate the study in patients with pain-related conditions. In the future, the underlying mechanism of acupuncture for its pain-modulating effects requires further careful and well-designed investigation. Dorsher [35] claims that the current evidence supports the neurological basis of acupuncture signaling instead of peri muscular fascia, mechanical and paracrine/autocrine mechanisms. More investigation is needed.

Conclusion

Acupuncture to the acupoint Houxi (SI3) can elevate the PPT, and this study developed a standard operating procedure for studying regional PPT in humans. The needling intervention was an important contributor to the effects of regional PPT on healthy participants. The effects on PPT at GV 4 & SI 11^L measurement regions were more pronounced. The study observed a statistical difference in regional PPT measurement changes among the 3 interventions. Finally, the clinical significance of the current research is that it critically evaluates several key aspects of clinical practice. It determines a clinical function of needling the acupoint SI3 in modulating general body pain. It also provides evidence that there are differential pain-modulating areas across the body, in that some regions obtained a more significant increase in pain threshold, which primarily occurred at related channel acupoints on the Small Intestine and Governing Vessel. The capacity of acupuncture to modulate pain is suggestive that it may be an alternative to opioid medication for pain. Acupuncture, as a nonpharmaceutical intervention, can have an important role in treating both acute and chronic pain. More recently, in 2021, the National Institute for Health and Care Excellence guidelines for chronic pain have recommended acupuncture as 1 of 3 interventions for longstanding pain [36].

Article information

Acknowledgments

The authors express their gratitude to all the healthy participants who took part in this study. Access to the UTS Chinese Medicine Clinic is also much appreciated.

Author Contributions

Conceptualization: CZ. Methodology: CZ and XW. Formal investigation: CZ and XW. Data analysis: XW. Writing original draft: XW. Writing - review and editing: XW, CZ, CEDL, and SZ.

Conflicts of Interest

This study was based on a thesis chapter presented to University of Technology Sydney as a PhD thesis. The thesis was published in the Open Publications of UTS Scholars (https://opus.lib.uts.edu.au/).

Funding

This research was supported by an Australian Government Research Training Program Scholarship.

Ethical Statement

The Human Research Ethics Committee approval (no.: ETH18-2294; 09 November 2018) was granted prior to commencing the study, and before enrolment. All study participants provided written informed consent.

Data Availability

Figure 1

Study schedule.

Figure 2

Diagram showing the flow of participants.

Figure 3

A boxplot for mean percentage (% PPT) change from pre-intervention scores for the 3 interventions from pre-intervention baseline scores (p < 0.0001 for both SI3m− and SI3m+ needling interventions).

Table 1

Schedule of Enrolment, Interventions, and Assessments

	Study period
	Enrolment	Allocation	Post-allocation						Close-out
Time point	Pre-intervention		Day 1		Day 8		Day 15		Day 22
	- Day 7	0	Pre	Post	Pre	Post	Pre	Post	Follow up
	Recruitment
Information sheets	×
Trial Entry Assessment	×
Enrollment
Trial Entry Assessment	×
Eligibility screen	×
Informed consent	×
Health Evaluation	×
Allocation		×
Interventions
SI3m+
SI3m−
SL
Assessments:
PPT			×	×	×	×	×	×
Reporting
Adverse reaction
Incident

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