Effect of acupuncture on experimentally induced itch
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1 British Journal of Dermatology (1987) 117, Effect of acupuncture on experimentally induced itch T.LUNDEBERG, L.BONDESSON* AND M.THOMAS Department of Physiology II, Karolinska Institutet and *Departmem of Dermatology, Karolinska Sjukhuset, Stockholm, Sweden Accepted for publication i June 1987 SUMMARY The effect of acupuncture on experimentally induced itch was studied in 10 healthy volunteers. Itching was induced by intradermal injections of histamine on the upper arm. 'Placeboacupuncture', acupuncture and electro-acupuncture at 2 Hz or 80 Hz were applied over the injection site, proximal to the injection site (in the same dermatome) or extrasegmentally (ipsilateral to the injected arm) for a period of 5 min following induction of itch. In addition, the effect of a 5 min period and a 20 min period of stimulation of the skin area prior to the induction of itch were studied. The same periods of stimulation were also applied to extrasegmental points prior to the induction of itch on the arm. and 2 Hz and 80 Hz electro-acupuncture significantly reduced subjective itch intensity when applied intrasegmentally. No significant effects were obtained when stimulation was applied extrasegmentally. The results suggest that acupuncture or electro-acupuncture could be tried in clinical conditions associated with pruritus. While several therapeutic procedures may relieve pain the possibilities of alleviating itch are fewer and often insufficient.^ It is a common experience that the perception of pain and itch may be changed by concurrent afferent input. This has been evaluated and confirmed in clinical experiments using transcutaneous electrical nerve stimulation (TENS) or vibratory stimulation.^'^ Furthermore, TENS and vibratory stimulation have also been observed to reduce experimentally induced pain and itch.*'^ An alternative method by which alleviation of pain may be obtained is electro-acupuncture.^ We have tested whether electro-acupuncture could reduce peripherally induced itch and compared the effect witb that obtained using acupuncture^ and 'placebo-acupuncture'. METHODS Subjects Ten healthy volunteers (seven males, three females), aged between 18 and 35 years took part in the study. Correspondence; Dr T.Lundeberg, Department of Physiology II, Karolinska Institutet, S Stockholm, Sweden. 771
2 772 T.Lundeberg, L.Bondesson and M.Thomas Experimental pruritus Itch was produced by histamine hydrochloride (ACO, Solna, Sweden) i /tg in a volume of ooi ml saline (0-9" o)) injected intradermally on the medial aspect of the upper arm.^ The size of the skin fiare was measured 5 min after injection. The fiare was outlined on the skin with a marking pen, traced onto a transparent plastic film, and the area measured planimetrically. Itch intensity as perceived by each subject was recorded continuously, for a maximum of 10 min, using a graphic rating scale. The scale consisted of a lever attached to a linear potentiometer which controlled the position of a pen on a chart recorder. The latter was not visible to the subject. The subjects were instructed to move the lever from the left, zero, position (o), indicating no itch, to a position indicating perceived itch intensity. The extreme right end of the scale (9) represented intolerable itch. Based on this continuous registration, the maximal itch intensity () and the itch duration () were measured. In order to obtain a cumulative measure of the total amount of itch perceived by each subject a total itch index (Til) was estimated. This index was calculated by measuring the area under the Experimental protocol Each of the 10 subjects was tested with 'placebo-acupuncture', acupuncture (with manual stimulation), 2 Hz electro-acupuncture and 80 Hz electro-acupuncture. The time interval between testing of the first three modes of acupuncture was about i week for all subjects. Between the third and the fourth mode there was an interval of approximately 4 weeks. At each session the subjects received eight intradermal histamine injections on the medial aspect of the upper arm, four in each arm. The first injection was not followed by any stimulation. The second was followed by 5 min of stimulation over the pruritic area. The third by stimulation approximately 10 cm proximal to the injection site (in the same dermatome, Lui and Lu2, Fig. i). The fourth injection was followed by 5 min of extrasegmental stimulation. The fifth injection was preceded by 5 min of stimulation over the site to be injected, and the sixth by 20 min stimulation over the site to be injected. The seventh and eight injections were preceeded by 5 min and 20 min of stimulation respectively at extrasegmental points Liv 5 and Liv 6 (Fig. i), ipsilateral to the injected arm. Stimulation techniques 'Placebo-acupuncture'. Two stainless steel acupuncture needles (38 cm long) were inserted superficially, one at Lu3 and one at Lu4 (Fig. i). None of the patients experienced any specific sensation on the insertion of the needles or during the experiments.. Theacupunctureneedles were inserted to a depth of cm after using skin sterilization procedures. The needles were then manipulated by rotating them back and forth through 180. This elicited sensations of local numbness and distension, heaviness, tingling or sensations radiating away from the site of needle insertion. These were generally uncomfortable but non-painful sensations, described as de Qi in traditional Chinese medicine. De Qi was further elicited by repeating the manoeuvre for approximately 10 s every minute during the course of acupuncture. Electro-acupuncture. The subjects received electrical stimulation of 2 Hz or 80 Hz continuously. The needles were connected to an acupuncture pulse stimulator (Delta Pro Med,
3 Effect of acupuncture on itch 773 (a) Lung 2 Lung Lung 3 Lung 4 FIGURE I. Location of the acupuncture points used. Lung (Lu) is the lung channel of hand-taiyin. Liver (Liv) is the liver channel of foot-jueying. (a) Pruritic area: Lu 3 is on the medial aspect of the upper arm, about 9 cm below the end of the axillary fold, on the radial side of m. biceps brachii. Lu 4 is on the medial aspect of the upper arm, about 3 cm below Lu 3, on the radial side of m. biceps brachii. Proximal: Lu i is below the acromial extremity of the clavicle. Lu 2 is in the depression below the acromial extremity of the clavicle. (b) Extrasegmental: Liv 6 is about 21 cm above the tip of the medial malleotus, on the medial aspect and near the medial border of the tibia. Liv 5 is about 15 cm above the tip of the medial malleolus, on the medial aspect and near the medial border of the tibia.
4 774 T.Lundeberg, L.Bondesson and M.Thomas TABLE 1. Effect of placebo-acupuncture, acupuncture and electro-acupuncture on maxima! itch intensity (), total itch index (), itch duration () and induced flare response (). The results are expressed as a percentage of unsiimulated controls. Values are means + SD Stimulation over injection site: Placebo-acupuncture 62 ± * Electro-acupuncture 2 Hz * 8a Hz 38 ±18** Stimulation proximal to injection site: Placebo-acupuncture ± 17* Electro-acupuncture 2 Hz 40 ± 16* 80 Hz 37± 11** Extrasegmental stimulation: Placebo-acupuncture ioi ± ± 24 Electro-acupuncture 2 Hz 76 ± Hz 112 ± 35 iio± ±34 74 ±30 48 ± 19* 98 ± ± ± ±29 99 ±39 83 ± ±36 78 ±29 91 ± ±30 IOI ± ± II2±27 93 ±26 98 ± ± 38 5 min pre-treatment stimulation applied over site to be injected: Placebo-acupuncture 71 ± ±27 76 ±27 92 ±24 Electro-acupuncture 2 Hz ±29 86 ±32 80 Hz 46 ± 22'' min pre-treatment stimulation applied extrasegmentally; MH TH Placebo-acupuncture 112 ± ± ±31 98 ±32 Electro-acupuncture 2 Hz 86 ±27 76 ± Hz 91 ±25 93 ± IOI ± ±27 20 min pre-treatment stimulation applied over site to be injected Placebo-acupuncture 79 ±27 93 ± ± ±33 88 ± ±32 Electro-acupuncture 2 Hz 112 ±30 93 ±30 94 ±29 80 Hz 98 ±26 79 ±23 78 ±34 20 min pre-treatment stimulation applied extrasegmentally Placebo-acupuncture Electro-acupuncture 2 Hz 80 Hz 130 ±39 93 ±27 86 ±30 79 ±27 99 ±29 89 ± ± 32 ii4±3i 97 ± IOI ± ± 37 IOI ± ±27 82 ± ±39 IOI ±26 93 ±34 79 ±29 99 ±34 79 ± ± ±37* 89 ±29 74 ± ± ±44* 157 ±52* ±30 92 ±36 P<0 05, ** P<o 01, compared with unstimulated controls.
5 Effect of acupuncture on itch TABLE 2. Time after start of treatment needed to obtain first sign of relief and maximal relief of perceived itch intensity 775 Time s (mean ± SD) Partial relief Maximal relief Mode of treatment Direct Intra Extra* Direct Intra Extra* Placebo acupuncture 43 ± ± 31 37±i ili±-i-] Hz Electro-acupuncture 39 ± ' Hz Electro-acupuncture " Treatment was applied for 5 min after itch had been elicited, either directly over the injection site (Direct), intrasegmentally, 10 cm proximal to the injection site (Intra) or extrasegmentally at Liv 5 and Liv 6, ipsilaterai to the injected arm (Extra). London, U.K.)> producing bipolar square wave pulses with a duration of 02 ms. The stimulus intensity was adjusted to about twice the perception threshold level. Statistical analysis Results obtained with acupuncture were compared with results at the unstimulated control site using Wilcoxon's matched pairs signed ranks test. RESULTS The results at the control sites show that following intradermal injection of 001 ml histamine, itch was elicited in every subject. The itch sensation increased rapidly, reaching maximal intensity within i min and thereafter slowly levelling off within 10 min. Following the histamine injection a wheal and flare reaction developed. In cases where the injection was accidentally given subcutaneously the wheal and flare always developed but without pruritus. The results are presented in Table i. Maximal itch intensity was reduced signiflcantly by electro-acupuncture at 80 Hz over or proximal to the injection site (P < 001). and electro-acupuncture at 2 Hz also reduced the itch intensity significantly (P<OO5). 'Placeboacupuncture' and extrasegmentally applied treatment also reduced itch intensity but less effectively than acupuncture and electro-acupuncture at 2 Hz. The shortest time needed to obtain partial and maximal depression of perceived itch (mean ± SD; 28 ± 11 s and 93 ± 41 s respectively) was obtained using 80 Hz electro-acupuncture over the injected area (Table 2). None of the stimulation techniques had any signiflcant effect on the total itch index. The duration of itch was also unaffected. However, the fiare responses accompanying the histamine injections were as a rule increased with most types of stimulation, without a relationship with itch reduction. The largest increases were obtained using 80 Hz electro-acupuncture. DISCUSSION The sensation of itch as well as of pain has been related to activity in thin, unmyelinated, polymodal C-flbre units. Also, certain substances released in the vicinity of the C-flbres can
6 776 T.Lundeberg, L.Bondesson and M. Thomas initiate the stimulus notably histamine and prostaglandins.'"" Hovfever, an increased stimulus frequency during direct intraneural electrical stimulation of C-fibres in humans does not transform the sensation of itch into pain.'" This finding, and the fact that electrical stimulation ofthe skin may produce itch in healthy subjects irrespective of stimulus frequency suggests that the activation of one population of C-fibres signals itch, while others signal pain. Also the participation in activity of A-delta fibres in peripherally induced itch has been suggested.'"^ Our study was designed to clarify the effect of acupuncture on induced itch with particular reference to site, timing and nature of stimulation. The results indicate that electro-acupuncture at 80 Hz applied within the same dermatomal segment as the pruritic area for a period of 5 min after the induction of itch produced the greatest reduction in itch intensity. No significant reduction of itch duration was seen. These results differ from those of Belgrade et al.^ whose experimental protocol involved the consistent use of three acupuncture points, one intrasegmental and two extrasegmental, with stimulation always 15 min prior to the induction of itch (the period of stimulation was not indicated). The difference in the results may be partly the result of differing experimental protocols in the two studies. However, the procedure which may have been nearest to these authors' design, 20 min of treatment prior to itch induction, did not significantly reduce itch duration in our study. Our results may perhaps be explained by the proposal that electro-acupuncture at 80 Hz activates large afferents more effectively (giving a higher firing rate) creating an inhibitory input that reduces experimentally induced itch.'"*^ The subjective nature of itch makes a placebo effect very possible. However, thefindingof an optimal treatment mode argues for a placebo independent mechanism. The results of the present study indicate that electro-acupuncture at 80 Hz may have a genuine effect at least in healthy subjects without underlying pathology. It is also of interest that a significant increase in the flare response was found when acupuncture stimulation was applied over the injection site. This might have been due to the additional effect of the local axon refiex often seen as a result of stimulation. The importance of the anti-pruritic effects of acupuncture on induced itch remain to be evaluated in clinical conditions. ACKNOWLEDGEMENTS This work was supported by grants from The Royal Swedish Academy of Sciences and Stiftelsen Clas Groschinskys minnesfond. REFERENCES 1 Winkelman RK. Pharmacological control of pruritus. Med Clin North Am 1982; 66: FjeUnerB,HagennarkO. Transcutaneous nerve stimulation and itching. Acta Dermato Venereol {Stockh) 1978; 58: Lundeberg T. Vibratory stimulation for the alleviation of chronic pain. Acta physiol i'carid (Suppl) 1984; 523: Ekblom A. Influence of electrical and mechanical stimulation in acute pain and in itch. Thesis, Stockholm Murray FS, Weaver M.M. Effects of ipsilateral and contralateral counterirritation of experimentally induced itch in human beings. J Comp Phys Psych I975; 89: Lundeberg T. A comparative study of the pain alleviating effea of vibratory stimulation, transcutaneous electrical nerve stimulation, electro-acupuncture and placebo. AmJ Chin Med 1984; XII: 72-9, 7 Belgrade MI, Solomon LM, Lichier EA. Effect of acupuncture on experimentally induced itch. Acta Dermato Venereol (Stockh) 1984; 64:
7 Effect of acupuncture on itch Fjellner B. Experimental and clinical pruritus. Studies on some peripheral mediators. The influence of ultraviolet light and transcutaneous nerve stimulation. Acta Dermato Venereot (Stoekh) 1981; 97 (Suppl): Ekblom A, Fjellner B, Hansson P. The influence of mechanical vibratory stimulation and transcutaneous electrical nerve stimulation on experimental pruritus induced by histamine. Aeta Physiot Scand 1984; 122: Hagermark 0, Strandberg K, Hamberg M. Potentiation of itch andflareresponse in human skin by prostaglandins E2 and H2 and a prostaglandin endoperoxide analog. J. Invest Dermatol 1977; 69: Hagermark 0, Strandberg K. Pruritogenic activity of prostaglandin E2. Acta Dermato Venereot {Stockh) 1977; 57: Torebjork HE. Afferent C-units responding to mechanical, thermal and chemical stimuli in human non-glabrous skin. Acta Physiot Scand 1974; 92: Shelly WB, Arthur RP. The neurohistology and neurophysiology of the itch sensation in man. Arch Dermatol 1957; 79: Wall PD. The gate control theory of pain mechanisms. A re-examination and re-statement. Brain 1978; 101: 1-18.
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Tetsuji WAKUDA, Masanao SHIBASAKI,Tadashi TANITSU* National University Corporation, Tsukuba University of Technology *Cooperation with research
NTUT Education of Disabilities, 2009 Vol. 7 Effects of Acupuncture on Control of Pruritus Associated with Atopic Dermatitis Course in Acupuncture and Moxibustion, Department of Health, Tsukuba University
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