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The Impact of Asynchronous Electroacupuncture Stimulation Duration on Cold Thermal Pain Threshold

Wang, Shu-Ming MD*; Lin, Eric C. BS†; Maranets, Inna MD*; Kain, Zeev N. MD, MBA‡

Section Editor(s): Liu, Spencer S.

doi: 10.1213/ane.0b013e3181ad9292
Analgesia: Pain Medicine: Brief Report

The durations of asynchronous electroacupuncture can affect the resultant hypoalgesia. Healthy volunteers were randomized to receive different durations (0 min, 20 min, 30 min, or 40 min) of asynchronous electroacupuncture stimulations (alternating low/high [2/100 Hz] frequency at 5 mA). Using a human experimental cold thermal pain threshold model, we found that 30 min of asynchronous 2/100 Hz stimulation resulted in the most significant hypoalgesic effect that was sustained for at least 60 min after stimulation compared with 0-, 20-, or 40-min stimulations (P < 0.05). We conclude that the most optimal duration for asynchronous electroacupuncture stimulation is 30 min.

From the *Department of Anesthesiology, Yale School of Medicine; †Department of Anesthesiology, The Yale Center for Advancement of Perioperative Health©, Yale School of Medicine, New Haven, Connecticut; and ‡Departments of Anesthesiology, Pediatrics, and Psychiatry and Human Behavior, University of California, Irvine School of Medicine, Irvine, California.

Accepted for publication March 27, 2009.

None of the authors have any relationships with any company or organization that has a potential or vested interest in the outcome of the study.

Partial data from this study were presented at the annual 2007 ASA meeting in San Francisco, California.

Address correspondence and reprint requests to Shu-Ming Wang, MD, Department of Anesthesiology, Yale School of Medicine, 333 Cedar St., New Haven, CT 06520. Address e-mail to

Acustimulations have been widely incorporated into a comprehensive clinical pain management program.1–9 Electroacupuncture stimulation (EAS) is a technique that applies a small electrical current to needles inserted into the acupuncture points.10 This technique is intended to achieve synergistic or additive analgesic benefits of traditional acupuncture and electrical stimulation.6,10 The advantages of EAS over traditional acupuncture manipulation include better quantification of the stimulation delivered and reproducibility.6 Asynchronous EAS was developed based on the findings that by alternating low and high frequency electrical stimuli (e.g., 2 Hz of electrical stimulation alternating with 100 Hz of electrical stimulation) through needles into acupuncture points enhances hypoalgesia more than either frequency alone.11,12 The duration of a single frequency of electroacupuncture affects the resultant hypoalgesia.3,4 We therefore conducted the following study to determine whether the duration of asynchronous EAS can also affect the resultant hypoalgesia using a human experimental pain model.

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After approval of the Human Investigation Committee of Yale School of Medicine, healthy volunteers (aged 18 yr and older) were recruited. Exclusion criteria included a history of any systemic medical or psychological illness, daily medication usage, illicit substance usage, prior experience in acupuncture, and pregnancy. All volunteers were informed that the purpose of the study was to test whether different durations of EAS can affect their ability to sense cold pain.

After obtaining informed consent and baseline demographic information, including State-Trait Anxiety Inventory, education and belief in acupuncture treatment, all participants were positioned on a stretcher comfortably in an experimental room with the temperature set at 70°F. To eliminate the possibility of bias by the subjects, no watch or clock was allowed in the study area. Using a Datex-Ohmeda portable patient monitor, the changes of hemodynamic variables, which included continuous heart rate monitoring and noninvasive arterial blood pressure measurements set at every 5 min, were recorded during the entire study period. The preselected sites were marked on the medial side of the right lower leg before the initiation of cold thermal pain threshold (CTPT). CTPT was delivered by PATHWAY (Medoc Medical, Israel) through a 3 × 3 cm Peltier thermal stimulation probe using advanced thermal stimulator version 2.4. The first research assistant assessed the baseline CTPT at these sites (Fig. 1) in a random order for a total of nine times (three times per site) as described in previous studies.3,13 All participants were instructed to press the “stop” button when they sensed the cold sensation turning into pain, and the corresponding temperatures were automatically recorded into the PATHWAY. The participants were randomized into one of the four durations based on a computer-generated randomization table. Only the acupuncturist knew that the number represented a selected duration of EAS. The acupuncturist then inserted the acupuncture needles (Siren, L type No 5 [0.25 × 40 mm], Shizuoka, Japan) into the selected acupuncture points on the left leg (Fig. 2). All participants were informed that they might or might not feel a “de qi”* sensation and/or a vibrating sensation during the intervention period. For participants assigned to the sham control group, i.e., 0 min group, the acupuncture needles were inserted superficially without eliciting any “de qi” sensation. For participants receiving 20-, 30-, or 40-min of EAS, the acupuncture needles were placed until the acupuncturist experienced a “de qi” sensation. The depth of needle insertion at that point was about 0.75–1.5 cm. Once the acupuncture needles were placed, the acupuncturist connected a pair of electrodes from a Han stimulator (Beijing, China) to the needles. Asynchronous EAS (2/100 Hz) was delivered via Han stimulator and the intensity gradually adjusted to 5 mA over a 3-min period. For participants assigned to receive 0 min of stimulation, the electrodes were connected to an inactive Han stimulator for 20 min. Only the acupuncturist had a timer, so the EAS would be terminated when the proper assigned duration of EAS was reached. None of the research assistants was present during the EAS period. Once the assigned EAS was completed, the State-Trait Anxiety Inventory-S was reassessed and the CTPT was immediately reassessed post-EAS, then subsequently every 5 min for a total of 60 min by the second research assistant at the same premarked sites. This procedure assured blindness of the research assistants to prevent bias.

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Statistical Analysis

The sample size was calculated based on a previous study14 in which the difference in mean visual analog scale scores for pain between volunteers who received real EAS versus those who received sham EAS was 0.65 with a standard deviation of 0.5. Based on our calculation, 14 subjects per group were needed to achieve a power of 90% in detecting 10% hypoalgesic differences between the treatment groups with an α value of 0.05. All hemodynamic and CTPT data were directly recorded into PATHWAY and exported into SPSS 16 for Mac (SPSS, Chicago, IL) and analyzed using repeated measure analysis with post hoc least significant difference and P < 0.05 considered to be statistically significant. Baseline demographic data and an anxiety questionnaire were analyzed using one-way analysis of variance.

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Fifty-six subjects participated in this randomized, controlled trial, and no subject withdrew from the trial. There was no difference in age, education, gender, anxiety, and level of belief in acupuncture among the groups (Table 1). There were no differences in the arterial blood pressure or heart rate among the groups before, during, or after EAS.

Because the durations of EAS were different, we only compared the differences in temperature at which volunteers sensed cold pain among groups between 40 and 80 min after the onset of intervention. As illustrated in Figure 3, participants receiving 30 min of EAS had significant hypoalgesia as compared with those receiving 0 min (P = 0.008), 20 min (P = 0.005), and 40 min (P = 0.024). The asynchronous EAS-induced hypoalgesia did not differ significantly between participants receiving 0 min vs 20 min (P = 0.59), 0 min vs 40 min (P = 0.57), and 20 min EAS vs 40 min of EAS (P = 0.69).

At 0 min post-EAS, participants in the 30-min group sensed cold pain at a significantly lower temperature than those who received 0 min (P = 0.01) and 20 min (P = 0.013) but not lower than those who received 40 min of EAS (P = 0.93). However, at 5 min post-EAS, the participants who received 30 minutes of asynchronous EAS reported sensing cold pain at a much lower temperature than those who received 0 min (P = 0.006), 20 min (P = 0.005), and 40 min (P = 0.03). The above phenomenon persisted for 60 min post-EAS (Fig. 3).

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Under the conditions of this study, we found that 30 min of asynchronous 2/100 Hz (5 mA) EAS at ST36 and SP6 resulted in significant hypoalgesia compared with 0 min, 20 min, or 40 min. The hypoalgesic effect was sustained for 60 min post-EAS. Similar to previous electrical stimulation studies,3,14 the asynchronous EAS-induced hypoalgesia is not restricted to segmental pain inhibition. As illustrated in Figures 1 and 2, EAS at left ST36 and SP6 (L4, L5, and S2 dermatomal distribution) and the hypoalgesia was tested at the right premarked sites (L3, L4, and S2 dermatomal distribution). A previous manual acupuncture study demonstrated that the peak of hypoalgesia was between 20 and 40 min sustained up to 60 min,15 and the peak hypoalgesia of single frequency EAS also occurred at about 30 min and was sustained up to 75 min during stimulation.4,16 We were not able to demonstrate the similar phenomena as described in these previous studies.4,15,16 In our study, the temperatures at which subjects perceived cold pain after receiving 40 min of asynchronous EAS were significantly higher than the temperatures in those who received 30 min of the same EAS. Future studies should explore the potential mechanism(s) contributing to the development of this phenomenon. Interestingly, the optimal duration for alternating frequencies of EAS as demonstrated in our study is the same as the time setting used in other electrical nerve stimulators that are commercially available to deliver alternating electrical frequency stimulations to the target nerves.5,9 Therefore, we speculate that the analgesia resulting from alternating frequencies of EAS, transcutaneous nerve stimulation, or percutaneous nerve stimulation may share a similar underlying mechanism.

The limitations of this study are as follows: 1) we did not assess the level of hypoalgesia while the stimulation was ongoing, thus we could not establish how the hypoalgesia developed over time, and 2) we did not have an “adequate” duration of CTPT assessment after stimulation. Based on a previous single frequency EAS study, the resulting hypoalgesic effects gradually return to control values within 35 min after termination of stimulation.16 As a result, we decided a priori to assess the CTPTs up to 60 min after EAS was terminated. In addition, the temperatures at which subjects sensed a CTPT were directly recorded into PATHWAY. Thus we did not discover that there was any fading even at 60 min post-EAS until after the study was completed and at the time of data analysis.

In conclusion, the duration of asynchronous 2/100 Hz EAS indeed affects the resultant hypoalgesia, and 30 min of stimulation seems to be the optimal duration.

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*A subjective sensation, described by subjects who received acupuncture treatment, as numbness, aching, soreness, or distension. From the acupuncturist’s perspective, this subjective sensation coincides with the sensation of the needle getting caught during application of acupuncture needle. Cited Here...

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