Kawakita Kenji, et al.. Japanese Acupuncture and Moxibustion, 2010; Vol.6(1): 92-97

The 2 nd JSAM International Symposium on Evidence-based Acupuncture

Physiological basis of therapeutic effects ofsham acupuncture in recent clinical trials
KAWAKITA Kenji1), Adrian White2)
1) Department of Physiology, Meiji University of Integrative Medicine
2) Plymoth School of University of Exeter, UK.
Abstract
Recent well-designed large scale RCTs of acupuncture on osteoarthritis of the knee, chronic low back pain andother musculoskeletal pain symptoms have clearly demonstrated that real acupuncture intervention actually workand their meta-analysis also confirmed that acupuncture therapy are more effective than conventional and/or usualcare. But there were no significant difference between real and so-called sham acupuncture. These results tend tolead a conclusion that acupuncture has no specific effect but it has strong placebo or expectation effect, althoughboth acupuncture interventions produced much greater clinical effects than conventional cares.
From physiological view points, sham acupuncture interventions such as minimal acupuncture, Streitberger orPark sham needle used in the clinical trials seem to be not inert intervention. Several sensory receptors could beexcited by these interventions. It should be noted that the response characteristics of polymodal receptors, whichwere assumed to be a possible sensory candidate for both acupuncture and moxibustion, are in accordance with thecandidate which activated by such sham interventions. So the actual clinical effect of so-called sham acupunctureintervention should be clarified by comparison with another type of inert sham/placebo acupuncture.
A RCT conducted in Japan using press tack needle (PTN), thin and short (0.18 mm in diameter, 0.6 mm in length)
needle attached to a plastic plate and its placebo one (only small metal ball attached instead of fine short needle)
were used to clarify a specific effect of real PTN
The main outcome measure was pain in VAS scale before and after triathlon race. Blinding of two types of PTN
to the subjects was also performed and the subjects could not discriminate real and sham PTN. Analgesic effects ofreal PTN were significantly much higher than the sham PTN. Moreover, recently Korean group examined the skintemperature of the knee in OA patients and found that real PTN produced a significantly much higher skin temperature increase by real PTN than that of sham PTN, and masking to both PTN was sufficient.
These results clearly demonstrated that clinical benefits of acupuncture have been well established, but its specificeffects should be confirmed by further studies using more reasonable sham devices.
Ⅰ．Introduction
Recent clinical trials of acupuncture on osteoarthritisof the knee and other musculoskeletal pain symptoms
have clearly demonstrated that real acupuncture treatments are significantly more effective than conventional
and/or usual care1-5), and their meta-analysis also confirmed the efficacy of acupuncture treatment6-7). A seriesof large scale clinical trials with high quality were conducted in German, and minimal acupuncture was used assham intervention which characterized by shallow needing to non acupuncture points without de-qi sensation8).
Figure 1 shows two typical results of German trials, andthere were no statistical significant differences between
the real and sham acupuncture groups. The minimal
acupuncture was assumed as inert intervention, and these

Corresponding author: Kawakita KenjiDepartment of Physiology, Meiji University of Integrative Medicine, Hiyoshi, Kyoto 629-0392, Japan
E-mail: k_kawakita@meiji-u.ac.jp

93Kawakita Kenji, et al.. Japanese Acupuncture and Moxibustion, 2010; Vol.6(1): 92-97

results tend to lead a conclusion that acupuncture has nospecific effect but it has strong placebo or expectation
effect, although both real and sham acupuncture treatment produced statistically significant much stronger
effects than conventional/ standardized therapies.
There are several issues still remain to be clarified forconcluding the lack of specific effects of acupuncture. If
the sham interventions used in these acupuncture trials
had some physiological effects, the conclusion might bedifferent, and the results should be re-considered as theresults of comparison of two different acupuncture procedures.
From physiological points of view, minimal acupuncture which penetrates the skin is difficult to assume asinert intervention. Several other sham acupuncture devices have been developed. Typical ones were developedby Streitberger9), Park10) and Takakura11). The tip ofneedle was blunt and the needle shaft was withdrawn
into the needle grip. When the sham device was tried toinsert the needle tip presses the skin and the needle
seems to be inserted into the deep tissues visually. Thesesham devices seems to be more reasonable for shamacupuncture, and several clinical trials have been conducted using these sham device12). So it is important
issue to examine these sham devices are physiologicallyinert or not.

In the present study, physiological potential of socalled sham acupuncture intervention was examined by
microneurogram technique focusing on the neural activity of polymodal receptors. Another type of acupuncture
and its sham/placebo called press tuck needle (PTN) wasintroduced and several results of basic and clinical studies were briefly introduced as a possible device of future
acupuncture research.
Responses of the polymodal receptors to sham acupuncture stimulation
Two young healthy subjects who gave written informed consent were used. The subject sat on the on bed
with side down position, and single unit discharges wererecorded from the peroneal nerve at the low leg withmicroneurography technique with a fine insulated needle(Frederick Hair 10 um, 180 μm, tungsten). The responsecharacteristics of the recorded unitary discharges to mechanical and thermal stimulation applied to the receptive
field, and its conduction velocity were measured andidentified as C polymodal-type receptor. The responsiveness of CMH (C mechano-heat) units to real PTN,
sham PTN and pressure with blunt needle (sham acupuncture) were examined.
Figure 2 demonstrates that a CMH unit responded toreal PTN transiently and no discharges were elicited by

94
Kawakita Kenji, et al.. Japanese Acupuncture and Moxibustion, 2010; Vol.6(1): 92-97

sham PTN application, however a phasic weak response
was observed when the attached tape was removed. On
the other hand, application of pressure with a blunt needle tip also activated the CMH, but this unit did not respond to tactile stimulation.
The majority of CMH units of the skin are considered

as polymodal receptor. The response characteristics ofthe polymodal receptors, which were assumed to be apossible candidate for both acupuncture and moxibustion,
are in accordance with the candidate, so it should bepointed out the fact that non-penetration sham acupuncture can activate the polymodal receptors of the skin.

95
Kawakita Kenji, et al.. Japanese Acupuncture and Moxibustion, 2010; Vol.6(1): 92-97

Effects of press tuck needle on the muscle sorenessafter the triathlon race.
The first RCT of PTN was conducted on the athletesof triathlon race13). The subjects were participants of atriathlon race (n=62), they were randomly allocated toreal and sham PTN. Ten PTNs were attached on the lowback skin bilaterally. Subjects were asked to answer thequestionnaire before, immediately after and 24 hours
after the race. Figure 3 indicates the results of PTN orsham PTN attached groups at 24 h after the race. A significantly higher pain relief was obtained by real shamthan those of sham control. And a survey on the maskingof real and sham PTN was also conducted. The results
clearly demonstrated that the subjects could not discriminate the real and sham PTN precisely (p<0.05)
Effects of real and sham PTN on skin temperature
Physiological effects of PTN were also examined using healthy volunteers (n=12). Real PTN and sham PTN
were attached to the skin around the knee joint and thechanges of skin temperature around the joints weremeasured by themography before and after the PTN
attachment. It is demonstrated that the real PTN produced a significantly higher skin temperature than sham

PTN. Masking of the real and sham PTN was also successfully performed. (unpublished data by Kim YS).
Increase of the skin temperature by real PTN suggestthat it induces axon reflex which medicated by C afferent fiber receptors.
Discussion
Various control interventions such as minimal acupuncture or sham acupunctures have been used in recent
clinical trials of acupuncture, and they induced similar
efficacy to those obtained by real Chinese style acupuncture treatment, which requires "de-qi" sensation by manipulation of needle, and no significant difference between real and sham acupuncture groups were detected.
In the present electrophysiological study, it is clearly
demonstrated that the sham interventions such as minimal acupuncture and non-penetrate sham acupuncture
could activate the polymodal-type C fiber receptors inthe skin ， The polymodal-type receptors have been
proposed as a candidate of acupuncture and moxibustion
stimulation14). Other somatosensory receptors such as
touch and pressure receptors were also excited by nonpenetrating sham acupuncture15), but they have no sensi-

96
Kawakita Kenji, et al.. Japanese Acupuncture and Moxibustion, 2010; Vol.6(1): 92-97

tivity to heat stimulus and their roles in acupuncture
action mechanism might be less important than thepolymodal-type receptors.
Polymodal receptors are responsive to mechanical,
thermal and chemical stimuli, which respond to pain
substances and sensitizing chemicals such as bradykinin
and prostaglandins. It is well known that they are activated by both acupuncture and moxibustion, The response characteristics of the polymodal receptors andtheir functional and morphological similarities to acupuncture/tender points were summarized in Table 1.
They offer a rational explanation to the issues of mysterious acupuncture points. In the long history of acupuncture and moxibustion, it is now clearly demonstrated thatmoxibustion therapy was older than acupuncture, and theconcept of meridians might be borne from the clinicalexperiences by moxibustion not by acupuncture.16) So,
touch and pressure receptors, which did not respond tothermal stimuli, could be excluded in the peripheral
action mechanism of acupuncture and moxibustion theoretically.
In comparison with sham PTN, the real PTN could activate the polymodal type receptor, and produces significantly stronger clinical efficacy on pain relief and skintemperature increment. The masking of real and sham
PTN were succeeded in both studies. Moreover, the PTN
seems to be much safer than those of penetration-type
real acupuncture as its shaft of needle is only 0.6 mm.
These results strongly suggest the usefulness of the real and sham PTN in future clinical trials to clarify thespecific effects of acupuncture therapy.
References
1) Berman BM, Lao L, Langenberg P, Lee WL, Gilpin
AM, Hochberg MC. Effectiveness of acupuncture as
adjunctive therapy in osteoarthritis of the knee: arandomized, controlled trial. Ann Intern Med. 2004;
141 (12): 901-10.
2) Witt C, Brinkhaus B, Jena S, Linde K, Streng A,
Wagenpfeil S et al. Acupuncture in patients with osteoarthritis of the knee: a randomised trial. Lancet
2005; 366(9480): 136-43.
3) Scharf HP, Mansmann U, Streitberger K, Witte S,Kramer J, Maier C et al. Acupuncture and knee osteoarthritis - a three-armed randomized trial. Ann Intern Med 2006; 145(1): 12-20.
4) Brinkhaus B, Witt CM, Jena S, Linde K, Streng A,
Wagenpfeil S et al. Acupuncture in patients withchronic low back pain: a randomized controlled trial.
Arch Intern Med 2006; 166(4): 450-7.
5) Haake M, Muller HH, Schade-Brittinger C, BaslerHD, Schafer H, Maier C et al. German AcupunctureTrials (GERAC) for chronic low back pain: randomized, multicenter, blinded, parallel-group trial with 3groups. Arch Intern Med 2007; 167(17): 1892-8.
6) White A, Foster NE, Cummings M, Barlas P. Acupuncture treatment for chronic knee pain: a systematic review. Rheumatology (Oxford) 2007; 46(3):384-90.
7) Manheimer E, White A, Berman B, Forys K, Ernst E.
Meta-analysis: acupuncture for low back pain. Ann
Intern Med. 2005; 142(8): 651-63.
8) Vincent CA. A controlled trial of the treatment ofmigraine by acupuncture. Clin J Pain. 1989; 5(4):305-12.
9) Streitberger K, Kleinhenz J. Introducing a placebo
needle into acupuncture research. Lancet 1998; 352:364-5.
10) Park J, White A, Stevinson C, Ernst E, James M.
Validating a new non-penetrating sham acupuncturedevice: two randomised controlled trials. AcupunctMed 2002; 20(4): 168-74.
11) Takakura N, Yajima H. A double-blind placebo
needle for acupuncture research. BMC Complement
Altern Med 2007; 7: 31.
12) Vas J, Mendez C, Perea-Milla E, Vega E, Panadero
MD, Leon JM, Borge MA, Gaspar O, SanchezRodriguez F, Aguilar I, Jurado R. Acupuncture as acomplementary therapy to the pharmacologicaltreatment of osteoarthritis of the knee: randomised
controlled trial. Br Med J. 2004; 329 (7476): 1216.
13) Kaneko Y, Furuya E, Akamoto A. The effects ofpress tack needle treatment on muscle soreness after
triathlon race -sham-controlled study JAM 2009; 6:22-30.
14) Kawakita K. and Gotoh K. Role of polymodal receptors in the acupuncture-mediated endogenous pain
inhibitory systems. In: Kumazawa et al. eds., Progress in Brain Research Vol.113, The polymodal receptor, Elsevier Science BV, 1996, pp 507-523.
15) Kagitani F, Uchida S, Hotta H, Aikawa Y. Manualacupuncture needle stimulation of the rat hindlimb
activates groups I, II, III and IV single afferent nerve
fibers in the dorsal spinal roots. Jpn J Physiol. 2005;
55(3): 149-55.

97
Kawakita Kenji, et al.. Japanese Acupuncture and Moxibustion, 2010; Vol.6(1): 92-97

16) Harper D. Early Chinese Medical Literature. The
Mawangdui medical manuscripts. 1 st ed. London:Kegan Paul International, 1998.