Abstract
BACKGROUND:
Acupoints are considered a dynamic functional area, which can reflect the internal condition of the body. In pathological states, disease-related acupoints are believed to be activated, which is known as acupoint sensitization.
OBJECTIVE:
This study aimed to investigate the major manifestations of acupoint sensitization in patients with chronic low back pain (cLBP) to provide better understanding of acupoint sensitization phenomena in the context of cLBP.
METHODS:
This study was a matched-sample cross-sectional study 16 participants diagnosed with cLBP and 16 healthy controls matched in age, sex, and ethnicity were included. The following aspects of sensitization phenomena of targeted points were compared: pressure pain threshold (PPT), skin temperature, surface electrical conductance, receptive field, and morphological change of skin.
RESULTS:
PPT at points of interest were significantly lower in cLBP participants compared with healthy controls (
CONCLUSIONS:
Reduced PPT at all detected points and enlarged receptive field at left BL 23 were found in cLBP participants. These two features appear key in defining acupoint sensitization in cLBP, and provide evidence for selecting and locating acupuncture points in future clinical studies.
Keywords
Introduction
Low back pain (LBP) is a universal health complaint with a global 1-month prevalence estimated as 23.2
Acupuncture has been reported to be cost-effective compared with usual care or no-intervention in a number of large clinical trials, and is strongly recommended as a first-line non-pharmacological therapy for cLBP by the American College of Physicians (ACP) in their practice guideline for LBP [5]. However, the manipulation of acupuncture is diverse and thus it is important to identify an optimal manipulation scheme to improve, and standardize, acupuncture practice in this area.
The acupoint is the primary component of the acupuncture system and choosing correct acupoints is a prerequisite of maximizing the effect of acupuncture treatment. Basically, the ‘correct’ acupoint should be more sensitive to stimulation than other points. According to our recent review [6], acupoints are considered a dynamic functional area, which can reflect the internal condition of the body. When the body is subject to pathological conditions, acupoints will be activated and transformed into a sensitized state, which presents as reduced sensation threshold, changed biophysical characteristics, enlarged receptive field, etc. Acupoint states are therefore changeable according to health status, a phenomenon known as ‘acupoint sensitization’. In addition, it’s also suggested that needling sensitized acupoints has a better clinical effect over stimulation of non-sensitized acupoints, since the modulation process of the central nervous system is more active [6]. Based upon this, differentiation of the ‘sensitized/non-sensitized’ state of acupoints under a specific pathological condition plays a crucial role in determining the points to be stimulated as part of treatment.
Based upon current theory, it is reasonable to propose that acupoint sensitization occurs widely in patients with cLBP; this may manifest as lower pressure pain threshold, changed temperature and skin conductivity, enlarged receptive field, and/or local tissue abnormality compared to healthy participants. In addition, sham acupuncture, especially needling at non-acupoints has been shown to be more effective than pharmacological and physical placebos, which means sham acupuncture is physiologically active, and is not inert enough to verify the specific effect of acupuncture treatment [7] (The glossary of related terminologies is presented in Supplementary Table 1). We aimed to explore these phenomena, by assessing markers of sensitization in designated acupoints and non-acupoints in people with cLBP, compared with healthy controls.
Methods
Study design
This study was designed as a matched-sample cross-sectional study, which included well controlled known confounding factors (age, sex, ethnicity) that may influence results [8, 9, 10]; patients diagnosed with cLBP and matched healthy controls were included. Controls were required to be individually matched with cLBP participants in respect of sex and ethnicity, and in terms of age within the range of
Location of BL 23, BL 25, BL 40 and non-acupoint.
Ethical approval for this study was granted by University of Otago Human Ethics Committee (reference no. H18/125), which was registered at Australian New Zealand Clinical Trials Registry (ANZCTR, registry no. ACTRN12619000614190p).
Participants were recruited from the University of Otago and Dunedin communities through leaflets, posters, or social media (Facebook, Twitter).
Eligibility criteria of patients with cLBP
Inclusion criteria
Adults, aged Met the diagnostic criteria of cLBP according to the NICE clinical guideline (No. 59), reporting pain duration of more than 3 months; Had intact sensation, and absence of altered sensation; Provided written informed consent.
Exclusion criteria
Had serious spinal disorders and history of spinal surgery; Took medications for LBP in the prior 1 week; Received acupuncture for LBP in the previous 4 weeks; Had co-morbid serious internal diseases; Had severe mental ill health; Unable to communicate in English or Chinese; Had severe disability and other pain; Were pregnant or in lactation period; Had skin damage or open wound on the points of interest; Had fever, or on anti-pyretic.
Healthy controls were recruited to match individual patients with cLBP in terms of sex, ethnicity, and age within the range of
Exclusion criteria (5), (6), (8), (9), (10) listed for patients were applicable for controls.
Points selection
Bilateral BL 23, BL 25, BL 40 were selected as routine acupoints of interest (i.e. for management of cLBP) based on clinical practice guideline [11], data mining results [12], our previous clinical trial, and expert experience. These points represent the main acupoints for cLBP regardless of the presence of radiating pain. In addition, we chose points at the same level with BL 25, and 2 cm lateral to the second side-line of bladder meridian, as designated non-acupoints [13] to assess whether acupoint sensitization was a specific phenomenon localized to routine acupuncture points of interest (Fig. 1). Detailed location of points are displayed in Supplementary Table 2.
Study procedure
A thermostat was set at 23 degrees Celsius and ambient humidity was maintained below 60% to ensure no moisture on the skin (this had been confirmed in our preliminary experiment); ventilation was also controlled to avoid direct airflow on participants. A total of 15 minutes rest was allowed prior to testing, to allow participants to adapt to the ambient environment. The indoor temperature and humidity were recorded by EasyLog (Lascar Electronics Ltd., Wiltshire, UK), to assess ambient conditions every 30 seconds throughout the study.
All measurements were conducted by the same practitioner (H.T.), to ensure consistency in approach. The practitioner was a registered acupuncturist in New Zealand with clinical experience of 5 years. The measurements followed the sequence: inspect skin surface of points; finger press to detect receptive fields and pathological tissues of points; 15-minute break; thermal camera used to detect the skin temperature of points; skin conductance meter used to measure skin electrical conductance of points; algometer used to measure the pressure pain threshold of the points. The points were measured in the order: Left BL 23, Right BL 23, Left BL 25, Right BL 25, Left BL 40, Right BL 40, Left Non-acupoint (NA), Right NA.
Observed morphology change of points
Participants were required to maintain a prone position, with arms lying alongside body, and fully exposed their lower back and popliteal fossa. Following identification and marking of standard acupuncture points with a washable marker, inspection was carried out under sufficient natural light to check for any tissue abnormality. Visual inspection is a straightforward approach used in previous research to detect morphological changes in skin color or skin texture of acupoints or meridians [14, 15]. The following manifestations were recorded with dichotomous data (Yes/No): change of skin color, skin integrity (desquamation, damage), and skin texture (hardness, glossiness, humidity, roughness).
Detected receptive fields and pathological tissues of points
The tip of the thumb was used to press downward slowly and moved around clockwise within a circular area of 2 cm diameter, centered on the acupoint. Moderate and even force was applied to guarantee equal stimulation on each point. Pressure was applied for 1 second with enough force to make a slight indentation in the skin, or slight skin color change from pink to white [16, 17, 18]. The most painful point was indicated by patients and marked with washable marker. In addition, pathological presentations of tissues such as nodule, streak, papula, or dimpling were identified by palpation. Palpation is a physical examination widely used in clinical practice to find myofascial trigger points by detecting subcutaneous nodules in the taut bands of muscles, and pressing these for pain reactions. A dichotomous response (Yes/No) was used to record these findings.
Detected surface temperature of points
MobIR
Thermal camera and manipulation.
A Diode laser THOR LX2
Skin conduction detector and manipulation.
Wagner FPIX™ Digital Algometer (FPIX25, Wagner Instruments, Greenwich, CT, USA) was used to quantitatively detect the pressure pain threshold (PPT) on each point with accuracy of
Participants received standardized instruction regarding the description of pain and pain intensity prior to starting the PPT test, to ensure they were able to distinguish pain threshold to a similar standard. Apart from the instruction necessary to guide participants through the detection process, the examiner didn’t provide any additional information related to their health issue, thus limiting potential confounding from the interaction. Participants maintained a prone position. After calibrating the initial figure on the algometer screen to zero, the 1 cm
Algometer and manipulation.
Numeric Pain Rating Scale (NPRS) [26], Roland-Morris Disability Questionnaire (RMDQ) [27], Screening Questions and Patient Health Questionnaire for Depression (PHQ-9) [28], Pain Anxiety Symptom Scale Short Form 20 (PASS 20) [29] were administered to detect participants’ health characteristics. These questionnaires have been verified to be of high reliability and validity (Supplementary Table 3).
Outcomes
Primary outcome
The primary outcome was difference of PPT between groups. PPT was defined as the minimal intensity of stimulus to induce initial pain that could be perceived by the person.
Secondary outcomes
Secondary outcomes included between group difference at acupoints in: (1) Skin temperature; (2) Skin conductance; (3) Receptive field: The presence of sensitized point’s location deviation from the center of the standard acupoint was compared between groups; (4) Morphology: the number and percentage of participants who were found to have changes in morphology was compared.
Sample size
R (version 3.5.1, R Development Core Team, New Zealand, 2018) was used to calculate sample size. Assuming SD for the differences in the primary outcome PPT between controls and cases was 150 Kpa [30], a sample of 16 matched-pairs of control and case participants was needed to achieve 80% power to detect a minimal clinically important difference (MCID) of 114.74 Kpa [31], using a paired-t test with a two-sided significance level of 0.05. Since this study used a one-time detection, there was no need to consider drop-out rate. For each case patient, a matching sample of 1 control participant was obtained, so 32 participants were required in total.
Data analysis
Means (standard deviations) or medians (interquartile ranges) were used to describe continuous variables as appropriate; frequencies and percentages were used to describe dichotomous or categorical variables.
Descriptive statistics were used to describe demographics and patient characteristics. In addition, paired t-tests were used to compare baseline characteristics (age, height, weight, BMI, PHQ-9, PASS 20) for comparability between matched pairs, assuming normal distribution within each group. Otherwise, signed Wilcoxon’s rank tests were used.
For primary analysis, the difference of PPT between two groups was analyzed by paired
For secondary analysis, paired t-tests or signed Wilcoxon’s rank tests were performed to estimate between-group differences of local temperature and electrical conductance as appropriate. McNemar’s tests were used to compare the presence of change of points’ receptive fields between matched pairs; if some cell values in contingency tables were added to be 0, descriptive analyses were applied instead. Descriptive statistics were used to describe the presence of morphology change; Outlier values were defined by boxplot, and handled with multiple imputation method.
Comparison of PPT between groups
Comparison of PPT between groups
All statistical analyses were performed using R (version 3.5.1, R Development Core Team, New Zealand, 2018); two-sided P value of less than 0.05 was regarded as statistically significant.
Recruitment and baseline analysis
32 participants (16 cLBP participants, 16 healthy controls) were recruited from 12
Results suggested that there was no statistically significant difference between groups in age, gender, ethnicity, height, weight, BMI, smoking status, alcohol consumption, or caffeine consumption. The cLBP group had higher PHQ-9 score with median (IQR) of 0 (6) versus 0 (0) in the control group, lower indoor temperature (22.13
Health characteristics
In the cLBP group, the maximum score of NPRS was 6/10, and the maximum score of RMDQ was 11/24. The mean (SD) of NPRS and RMDQ were 3.76 (1.75) and 5.25 (3.32), respectively. Consequently, the average state of disease severity of cLBP participants was moderate pain intensity and slight functional impairment [26]. In addition, 5 cLBP cases (31.3%) reported combination of sciatica radiating from lumbar to lower extremity.
In the control group, participants were all in general good health and had no low back pain. The median score of participants’ self-rated health condition was 9 (out of 10).
Primary outcome
Results indicated there were between-group differences in PPT of eight points, and PPT of all detected points was lower in cLBP group compared with healthy controls (
Secondary outcomes
Skin temperature
Skin temperature at detected points was variable compared to controls: the average temperature at L BL 23 (36.11 (1.62)) and R NA (33.65 (1.72)) were higher in the cLBP group, while the other six points were shown to have lower temperature. However, none of these differences were found to be significant (Supplementary Table 4).
Skin conductance
The median values of skin conductance on eight detected points seemed to be consistently higher in cLBP group. However, there are variances in data, and signed Wilcoxon’s rank tests suggested such differences were not statistically significant (
Acupoint’s receptive field
Out of 16 participants in each group, change of receptive field on L BL 23 was found in 8 (50.0%) of cLBP cases, and 2 (12.5%) healthy people. McNemar’s test indicated there was statistically significant differences in receptive fields in L BL 23 between groups (
Change of morphology
As the numbers of participants who presented positive results in changes of morphology were very low, only descriptive analyses were considered appropriate for these data.
There were 3 (18.8%) cLBP participants who exhibited change of skin color; by contrast, there was no change of skin color found in any participant in the control group. Two (12.5%) cLBP participants exhibited desquamation (skin was dry and flaking) on the lower back; no such changes were seen in the control group. Four cLBP participants (25.0%) displayed evidence of hardened tissues upon palpation of acupoint BL 40, in the shape of a streak or nodule. Only one participant in the control group was found to have subcutaneous nodules on bilateral BL 40.
Safety analysis
There was no adverse event in this study, so the study was regarded as safe.
Discussion
This study found significantly lower PPT at all detected points in participants with cLBP, compared with points on healthy controls. As the primary outcome of this study, findings supported the hypothesis that points of interest were in a sensitized state in the presence of low back pain.
There is evidence for a range of potential mechanisms underlying sensitization of acupoints, including alteration of sodium-gating [32, 33], purine-mediated hypersensivity of dorsal horn neurons [34], activation of DRG via increased currents in C-fibres [35], and elevated level of inflammatory transmitters [36].
The reduced PPT at non-acupoints in our study suggested central sensitization (CS) as a mechanism in the context of cLBP. CS refers to amplification of central neural signals that results in a wide spread of pain sensitivity across areas controlled by peripheral nerves, which is recognized as extraterritorial pain [37, 38].
This is important, as effectiveness studies frequently use non-acupoints as ‘sham acupoints’ in control groups, i.e. needles are inserted into supposedly inert points, which is called sham acupuncture. However, many studies have reported that acupuncture at sham acupoints was more effective than other physical placebos and no treatment [7, 39]. According to our results, this may be explained in that non-acupoints also become more sensitive to stimulation. This shows that using non-acupoints as sham controls might not be appropriate in clinical studies, as it might underestimate the true effect of experimental therapy.
Our study found an enlarged receptive field at Left BL 23 in cLBP participants. BL 23 is the Back-Shu point of kidney, therefore, it’s more sensitive in corresponding to back pain. Receptive field refers to the skin area associated with a specific neuron, with signals transmitted by peripheral afferent nerves [40]. In this study, the center of acupoints was found movable, which means the selection of acupoints might not be accurate when stimulating acupoints at fixed original location. Since this neglects the dynamic nature of acupoints, so it might not be an optimal scheme to perform acupuncture: Zhang, et al., indicated that stimulating receptive field significantly inhibited neuronal responses to nociceptive visceral pain, and was more effective than stimulating routine acupoint [41].
Given this, palpation plays an important role in accurately locating the acupoint. Firstly, due to the expansion of receptive field, the acupoint might deviate from the original location; secondly, locating acupoints on the back mainly depends on the accurate identification of bony landmarks, which is usually determined by physical palpation. However, a systematic review suggested that most spinal palpatory procedures are unreliable, including accurate identification of the lumbar spinal segment [42]. This might result in inaccurate locating of standard acupuncture points; in contrast, palpation around designated acupoints enables the practitioner to better identify the sensitive and correct points to stimulate. Applying manual palpation to guide the selection of acupuncture points is not only proposed from the perspective of Traditional Chinese Medicine, but is also recommended by physiotherapists [43].
The negative results for skin temperature, skin conductance, and morphology suggested that the change of these outcomes was not as sensitive as PPT in the context of cLBP, and that small sample size was not adequate to detect potential differences. The potential clinical utility of these measures is limited given effect sizes are likely to be small. By comparison, PPT has shown superiority in detecting sensitized points with great sensitivity. The reading of skin temperature and conductance might also be influenced by ambient temperature and humidity, we took measures to control ambient temperature. Despite this, a statistically significant difference was found between the two groups. However, the absolute difference of ambient environment was considered small (1.33 degrees Celsius of average temperature difference and 7.81% of average humidity difference). These differences were not considered material nor physically relevant to the outcome measures.
On the basis of these findings, PPT may be recommended as a useful means for detecting and locating sensitized acupoints in routine clinical practice, and for future research. It is simple and straightforward to perform, and does not require special equipment or training. These findings do not support alternative means of assessment and detection of points (such as skin conductance, temperature), however further studies are required as we didn’t power the current study for these secondary measures.
This study had some limitations. First of all, not all points on the back pain related meridian were investigated. This study focused on the most commonly used and verified points, particularly as the results aimed to inform selection of (and feasibility of accurately locating) points in a future acupuncture clinical study It therefore does not definitively confirm the potential distribution pattern of acupoint sensitization Secondly, this was a single-center study in a teaching clinic with a relatively small sample size, so the generalizability of these findings should be treated with caution. Thirdly, while we tried to limit bias by using standardized criteria, subjective measurements were applied for outcome ‘morphology change’ and ‘receptive field’.
The PPT at acupoints and non-acupoints were significantly reduced in participants with cLBP however, their differences remained unclear as this study was not powered to detect significant differences in sub-groups. To address the differences between acupoints and non-acupoints requires another specific study design to include different parameters, with adequate statistical power. This can be considered for future research.
Conclusion
This study indicated that PPT at back-pain related acupoints were significantly lower in cLBP participants compared with matched healthy controls. In addition, it was found that the receptive field became larger at the left BL 23 acupoint in cLBP patients. These two features will inform selection and location of acupoints in future clinical studies. Larger sample size studies are required to further investigate any changes of electrical conductance, skin temperature, and morphology in the context of acupoint sensitization.
Authors’ contributions
H.T. was involved in study conception, design, administration, drafting, and revising manuscript; S.T., C.C., L.L., and G.D.B were involved in improving study design, supervising the study, and reviewing manuscript critically; R.O. was involved in assisting with research. All authors have read and approved final manuscript to be submitted.
Funding
This study was supported by a Ph.D. budget from the School of Physiotherapy, and H.T. was supported by a Ph.D. scholarship from University of Otago.
Supplementary materials
The supplementary files are available from https://dx. doi.org/10.3233/BMR-210297.
Footnotes
Acknowledgments
The authors sincerely thank Dr. Rajesh Katare, Department of Physiology, University of Otago, who provided a thermal camera for this study.
Conflict of interest
The authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article.
