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PUBBLICAZIONE PERIODICA BIMESTRALE - POSTE ITALIANE SPED. IN A. P. 45% ART. 2 COMMA 20/B LEGGE 662/96 AUT. 584/DC/DCI/CN - ISSN 0026-4806 TAXE PERÇUE Efficacy of wrists overnight compression
(HT7 point) on insomniacs:
possible role of melatonin?
Aim. Insomnia is a major problem which
Department of Medical Physiopathology decreases life quality. Many causes are involved
University of Rome “Sapienza”, Rome, Italy with it and anxiety is often associated. The
underlying mechanism is not completely
understood, even though different factors seem
to be associated. Among them melatonin and its
circadian rhythm is thought to have an impor-

insomniacs, at a higher extent than in the pla-
tant role. In addition, acupressure and acu-
cebo group. In addition, the 24 hours urinary
puncture are known to ameliorate insomnia
melatonin metabolite rhythm, obtained at the
and anxiety, when a specific wrist point is sti-
end of treatment, was considered as being nor-
mulated (HT7 Shenmen). With these bases, the
mal in a higher percentage of H7-treated
aim of the present study has been to evaluate
patients, with respect to the placebo group.
the efficacy of an acupressure device, “H7-
Conclusion. It is plausible to hypothesize that
insomnia control”, positioned on HT7 points,
the wrist acupressure device might be consi-
during the night, in terms of general health
dered a valid tool, without adverse effects sin-
and anxiety levels, together with the evalua-
ce it does not contain pharmaceutical products,
tion of sleep quality and the urinary melato-
that is able to naturally ameliorate sleep quality
nin metabolite 6-hydroxymelatonin sulphate
in insomniacs, acting through a not jet com-
determination, in a number of insomniacs.
pletely clarified mechanism, that may involve
Methods. Forty patients with insomnia were
melatonin.
divided into two groups and randomly received
Key words: Acupressure - Sleep Initiation and
either the H7 or placebo treatments, in a dou-
Maintenance Disorders - Anxiety - Melatonin -
ble-blind protocol, for 20 nights. Before and
after treatments every subject answered a series
of questionnaires (General Health Question-
naire 28 items; State-Trait Anxiety Inventory;
Pittsburgh Sleep Quality Index) and collected 24

Acute or chronic lack of sufficient sleep h urines, divided into two samples of 12 h each.
quality and quantity is defined as insom- Urinary melatonin metabolite was then deter-
nia and may induce loss of well being asso- mined using a RIA method.
ciated with a decreased quality of life.1 Many Results. Data obtained indicate that the device
H7-insomnia control is efficacious to ameliorate
aging, stress, chronic illnesses, with anxiety quality of sleep and reduce anxiety levels in
being associated most of the times, resultingin a more evident problem.2 Results from Received on September 25, 2008.
Accepted for publication on October 13, 2008.
the literature indicate a high frequency rateof insomnia in the older population, how-ever recent data indicate an increased insom- Corresponding author: M. Nordio, via Flaminia 29, 00196 Rome, Italy. E-mail: [email protected] nia rate in almost every age, and in fact pharmaceutical products for insomnia seem generally, acupressure) efficacy as a thera- to be the most used therapeutic agents. Data py for insomnia in general, and particularly from Italy indicate that roughly 34% of total when associated to anxiety.14, 15 In fact, elec- population has chronic insomnia problems, increased sleep quality, both subjective and sional insomnia.3 Mean age is usually around objective, and the decrease of anxiety levels, 55 years or older; however, it seems that it with the stimulation of a particular acupunc- is progressively decreasing, possibly due to ture point called HT7 Shenmen (the gate of an increased anxiety level in younger sub- the spirit), located on the outer side of the jects. From this point of view, most authors wrist, on the radial side of the flexor carpi ulnaris tendon, between the ulna and the strate a reduced ability to maintain sleep, pisiform bones.16-18 Acupuncture is used in the treatment of a variety of mental disor- ders, such as absent mindedness, insomnia, disturbing dreams, hysteria, depression, agi- mented, with respect to normal sleepers.
tation, and mental illness. It is also used in Biochemical modifications include the rela- the treatment of heart disease and fatigue.
ergic systems, and melatonin rhythm alter- through acupuncture nails or, more easily, ations.4, 5 As far as the latter is concerned, it is well known that the secretion of this mol- pointed device (i.e. pen, pencil), for a suf- ecule, produced by the pineal gland main- ly during night-time, follows a circadian which the beneficial effects are obtained is rhythm and has also the strong ability to the external environment.6 Therefore, it is ever, recently insomniacs treated with clas- possible to state that any condition that may sic acupuncture demonstrated a significant increase in sleep quality, in association with secretion rhythm, is then capable to modi- the increase of nocturnal melatonin levels.17 In addition, it has been hypothesized that the included.7 Data obtained to date indicate effects of HT7 stimulation may be mediated through opioid peptides production, rein- pathological factors may be able to deter- forcing, once more, the known interaction which has a protective role during stressful process (melatonin levels physiologically On the basis of these considerations, the decrease), stress, jet-lag syndrome, light aim of the present study was to evaluate the exposure at night, shift workers, electro- efficacy, tolerability and “easy-to-use” level of an experimental acupressure device called drugs use (i.e. non-steroidal anti-inflamma- “H7-insomnia control” (roughly, a soft rubber tory drugs [NSAIDs], and beta-blockers).8-10 pin, kept in place by an adhesive plaque), Melatonin administration to these subjects is positioned on HT7 point, in insomniacs, using self-administered well-known questionnaires.
In addition, the urine melatonin metabolite 6- rate global subjective sleep quality, while hydroxymelatonin sulphate (aMT6s) has been reducing the number and length of noctur- measured in the same patients, at the end of the treatment period, in order to ascertain More recently, increasing data of the lit- the presence (or absence) of a definite mela- Materials and methods
position of the true HT7 point, and 20 indi-cating another site, different from HT7, for wrist application. The sequence of the 20+20(true HT7 and placebo) sites was random- ized and the randomization key was unknown to the principles stated by the “Helsinki de- to the study crew and to the patients.
claration” and the “Good Clinical Practice”, patients collected two urine samples: the first defined by the International Conference of between 08:00 h and 20:00 h of the last day of treatment, immediately before the last night; the second between 20:00 h and 08:00 mental design, H7 acupressure device vs h of the last night, till the next morning. The insomnia. In particular, the patients enrolled stored (-20° C) until the aMT6s melatonin wrist acupressure device “H7-insomnia con- munoassay method, as described further. In trol” (briefly, H7; Consulteam s.a.s., Como, addition, all patients were asked to give their Italy) which was positioned either on HT7 written impressions and personal evaluation point of both wrists (treated group), or on a concerning the use of the device (easiness of “non-HT7” point located in a different posi- use, clearness of written instructions, etc.).
tion of both wrists (placebo group), known Furthermore, they were submitted to the final as not to interfere with insomnia and/or anx- physical examination and fulfilled again the iety. Accordingly to previous data of the lit- three questionnaires described earlier. Data erature, which indicate in one to two weeks (aMT6s, day [D] and night [N] concentrations) improvement of sleep quality and melatonin and as night to day levels ratio (N/D) in order rhythm following acupressure of the appro- to identify patients with a conserved (N/D priate point, the treatment was prolonged ratio higher than 3) or altered melatonin rhythm (N/D lower than 3). Data, expressed At enrolment (T=0), after being informed of as mean ± SD, have been finally processed to the scope of the study and their role in it, and ascertain whether statistical differences among the “Informed Consent” being signed, each patient underwent physical examination in priate methods (Student’s t test).
order to ascertain inclusion and exclusion cri-teria, as described in the next paragraph of this paper, and were administered three interna- tionally used questionnaires to evaluate thelevel of global life quality of the individual A patient was included in the study accord- (General Health Questionnaire, GHQ28), the level of sleep quality (Pittsburgh Sleep Quality Index, PSQI), and the level of anxiety (State — absence of important pathologies, par- numbered (1 to 40) envelope containing the ticularly renal and/or liver failure. In parti- cular, creatinine levels should be within the wrists, sufficient for the entire 20 nights peri- od, and was instructed to apply the device on both wrists at exactly 22:00 h each night.
the study, together with availability and Moreover, each envelope also contained writ- ten instructions on how to assemble and apply the device in the correct way: 20 indicating the ing to the method described by Arendt et al.21Briefly, each urine sample (or standard) was It was impossible to enroll a patient in the prepared by diluting the appropriate amount presence of only one of the following fac- in order to obtain a final dilution of 1:250. An amount of 500 μL was then added to assay — lack of any of the “inclusion criteria”; tubes, in duplicate. Then, 200 μL of a specific — subjects working as “shift workers”.
antiserum were added to the samples (or stan- — intercontinental flights flown less than dards, except total counts and non-specific binding tubes), vortexed and incubated at room temperature for 30 min. The sheep anti- serum used in the assay AB/S/06 was suffi- — psychiatric illnesses, seasonal affective ciently specific for clinical application, with- out pre-assay sample preparation. The coef- ficients of variation intra- and inter-assay were 6.8% and 10.2%, respectively, and the limit of sensitivity of the assay was 0.5 ng/mL. After incubation, all the tubes received 100 μL 131I- Patients treated with benzodiazepines for aMT6s, then vortexed and incubated for 18 insomnia were permitted to continue their hours at 4° C. The separation between the usual therapy, possibly reducing it, depend- antibody-bound aMT6s and the free fraction ing on doctor’s decision. Moreover, if a was obtained by incubation for 15 min at 4° patient resulted on therapy for a chronic ill- C on ice, with 500 μL activated dextran-coated ness, the relative drugs, when not interfering charcoal, stirred continuously on ice 30 min with the protocols, were also permitted.
before and during addition. After quick vor-tex, in order to reduce intra-assay variation, the tubes were centrifuged at 3 000 rpm for 15 min at 4° C. The supernatant was finally tions of the aMT6s melatonin metabolite in removed and each tube counted for 1 minute.
urines derives from three considerations.
The aMT6s concentration in the samples was Firstly, urine collection is far more easier for determined from the standard curve and the the patients than day and night (at 03:00 h) blood collection, therefore a higher compli-ance was expected. Secondly, data of the lit-erature indicate that urine melatonin metabo- lite excretion parallels melatonin bloodrhythm, and responds to pineal melatonin Total number of patients included into the production blockade.21 Thirdly, the aim of study was 40 individuals, aged 49-77 years the present study was not an accurate descrip- (mean 64.05 years), 24 females and 16 males.
tion of melatonin rhythm phases, but simply In addition, 7 subjects (2 females and 5 males) the evaluation of its presence (or absence) decided to abandon the study; therefore, by after treatment, in each subject. For this rea- the end the effective number of patients used son it was also decided to present the results for the final evaluation was 33, 22 females and also as night/day ratio and to identify the 11 males. The group treated with H7 was ini- value of “3” as a cut-off point to divide indi- tially of 20 patients (11 females and 9 males), as viduals with a sufficient melatonin rhythm it was the placebo group (20 patients: 13 from those with a lower value that, there- females and 7 males). In the same groups, after fore, may have an altered melatonin rhythm, dropouts, the numbers were respectively 11 females and 7 males (H7), and 11 females and 4 males (placebo). Taken together, the data indicate that it has been possible to evaluate a kit (Stockgrand Ltd., Guildford, UK), accord- group of 33 individuals, 18 treated with H7 (11 Figure 1.—Mean ± SD scores (arbitrary scale, see the text Figure 2.—Mean ± SD scores (arbitrary scale, see the text for values) from the STAI (“trait” arm) questionnaires, for values) from the STAI (“state” arm) questionnaires, before and after H7 or placebo treatments, in insomnia before and after H7 or placebo treatments, in insomnia patients. *: P=0.0005 (H7 before vs H7 after); NS: not sig- patients. *: P=0.0004 (H7 before vs. H7 after); **: P=0.0005 (placebo before vs placebo after).
females and 7 males) and 15 treated with place- bo (11 females and 4 males). It is interesting tounderline that most of the patients which decid-ed to abandon the study, were in the placebo group (5 out of 7), with respect to the H7-treat- ed group (2 out of 7) (Figure not shown).
As stated in the protocol, at the beginning and the end of the study, the patients wereasked to answer a series of internationally val- idated questionnaires, in order to evaluatetheir subjective response to both treatments (H7 and placebo). The use of the GHQ28 indi- Figure 3.—Mean ± SD scores (arbitrary scale, see the text cates that the patients treated with the H7 for values) from the STAI (“trait” arm) questionnaires, device, after 20 days obtained a statistically before and after H7 or placebo treatments, in insomniapatients. *: P=0.001 (H7 before vs H7 after); **: P=0.003 significant better score, with respect to the (placebo before vs placebo after).
placebo group, indicating a more evident gen-eral well being sensation (H7: from 7.72±2.97to 4.72±2.74, P=0.0005; placebo: from from the “State” arm of the questionnaire 7.00±2.47 to 6.13±2.13, P=0.07 NS) (Figure 1).
indicate a reduction of anxiety level in both As far as the second questionnaire is con- considered groups. In particular, the reduc- cerned, the STAI, its purpose was to evaluate tion was highly significant in H7-treated the anxiety level of each subject, before and patients (before: 49.27±8.00; after: 40.11±7.06; after treatment. In addition, it has been possi- P=0.0004). Nonetheless, a significant reduc- ble to identify either the level of the so called tion, whilst of a lesser degree, was also pre- “State anxiety” (defined as non-habitual emo- sent in the placebo-treated group (before: tional stress), and the “Trait anxiety” (intend- 46.80±9.83; after: 42.80±10.19; P=0.0005). The ed as a more “fixed” characteristic of the per- results from the “Trait” arm indicate a similar son, or anxious character). Results obtained response in terms of anxiety level reduction Figure 4.—Mean ± SD scores (arbitrary scale, see the text Figure 5.—Day and night mean ± SD urinary melatonin for values) from the PSQI questionnaires, before and after metabolite aMT6s concentrations (ng/mL) in the H7 and H7 or placebo treatments, in insomnia patients. *: placebo groups. *: P=0.004 H7 day vs H7 night; **: P=0.01 P=0.00003 (H7 before vs H7 after); **: P=0.0006 (placebo before vs placebo after); ***: P=0.016 (H7 after vs placeboafter).
in both groups, however of a lesser extent (H7; before: 53.39±10.16; after: 50.72±10.75; bo group subjects. The difference was sta-tistically significant (H7: 3.83±1.29, placebo: P=0.001) (Placebo; before: 48.40±10.39; after: 2.53±1.64; P=0.008) (Figure not shown).
46.40±10.77; P=0.003) (Figures 2, 3).
xiety level scores, after treatment, was more Urinary sulphate-melatonin evaluation evident in patients treated with the H7 device, with respect to those treated with placebo, but the difference was not statistically signi- above, using a radioimmunoassay procedure on the 24 hours urine samples (divided into questionnaire demonstrated that sleep qual- Therefore, aMT6s concentrations have been ity was significantly higher at the end of the measured in 33 patients, with a total of 66 study, both in H7 and placebo patients (the samples. Results are expressed as mean ± lower the score, the highest the quality of SD of ng/mL urines. In addition, due to the sleep) (H7: from 11.44±2.57 to 6.61±2.97, wide physiological interindividual variability of aMT6s concentrations, and in the effort to 8.86±2.82, P=0.0006). However, the score reduce these differences, results are also reduction in H7 patients was significantly expressed as a ratio between night (N) and more evident than the reduction obtained in day (D) values. This N/D ratio has been con- the placebo group (P=0.016) (Figure 4).
Finally, at completion of the treatment peri- the contrary, a result lower than 3 indicated od, all subjects were asked to fill a specific an alteration of the normal melatonin rhythm.
questionnaire designed to give a global sub- Similarly to the questionnaires processing, jective evaluation of the wrist acupressure results obtained have been statistically ana- device they used in the study. A score accord- lyzed using the Student’s t test, when appro- ing to an arbitrary scale (0=insufficient; priate. Therefore, the evaluation of data obtained first of all confirmed the physiologi- cal difference between nocturnal and diurnal aMT6s in most subjects. In particular, patients Figure 6.—Night and day mean ± SD urinary melatonin Figure 7.—Percentage of subjects treated either with H7 or metabolite aMT6s ratio in the H7 and placebo groups. *: placebo having an aMT6s N/D higher than 3. Numbers in parentheses express the amount of patients with N/D ratiohigher than 3, with respect to the total number of indi-viduals in each group.
treated with the H7 device demonstrated aday/night melatonin rhythm that seems to be centrations were determined only at the end more pronounced, with respect to the place- of the treatment period, therefore impeding a bo group, and this difference was statistically significant (H7: day 5.25±5.79 ng/mL, night after treatment. However, it is authors’ opi- 20.50±16.18 ng/mL; placebo: day 4.52±2.56 nion that having only one melatonin metabo- ng/mL, night 9.68±5.62 ng/mL; P=0.01) (Figure lite rhythm (D and N values) determination at 5). Data evaluation as N/D ratio confirms and the end of the study, the comparison between amplifies these differences (H7: N/D 5.24±3.32, the number of patients with a correct mela- placebo: N/D 2.56±1.42; P=0.004) (Figure 6).
tonin rhythm in the H7 and placebo groups Data from the questionnaires indicate that melatonin rhythm is concerned (aMT6s equal most parameters were positively modified by H7 of higher than 3), the results indicate a per- treatment, and, in particular, a higher general centage of 54.5 (18/33). However, when the wellness level, a reduction of the anxiety level, an increase of the subjective sleep quality, with patients showing a normal melatonin rhythm respect to the placebo group. However, in con- was significantly higher, with respect to those junction with the ameliorating action of H7, a similar positive effect, on a smaller number of parameters, was also noted in the placebo-treat- ed patients. In particular, data obtained using the adverse reactions that could be associated to STAI and the PSQI questionnaires indicate that, besides the significant reduction of the anxietylevels and increase in sleep quality in the H7group, a similar reduction and increase, whilst Discussion
of a lesser extent, were documented also in the The overall efficacy evaluation of the wrist placebo group. Therefore the H7 effects on acupressure device “H7-insomnia control” on these parameters could be interpreted as “place- insomnia seems to be positive, even though bo effects”. However, this seems not the case, some limitations apply. The first concerning due to the fact that, first of all, the device was the small number of patients, and the second identical for all patients of the two groups and derived from the design of the study itself. In they were instructed in the same way on how fact, due to organizing, timing, and compli- the device should be correctly assembled before ance reasons, the melatonin metabolite con- positioning it on both wrists for the night. The great importance given to the preparation and insomnia control demonstrated to be able to the correct positioning of the device was cho- sen to contribute to the creation of a sort of effi- cacy expectation in both groups. Therefore, in increased subjective well being, sleep quality, this view it is possible to explain the signifi- cantly positive effect of the placebo treatment in — the fact that the same device, diffe- ameliorating the score of some aspects of STAI and PSQI questionnaires. However, it is impor- demonstrated an effect on some subjective tant to underline that the positive effect of H7 parameters, similar to the HT7 location (even treatment, especially when sleep quality is con- though to a lesser extent), indicates that pre- cerned, was significantly amplified, with respect liminary activities to its use, as assembling to the results obtained in the placebo-treated and attention to its placement may have a subjects. In this view, the subjective global eva- luation of easiness of use and efficacy of the device was considered significantly higher in increase of sleep quality after treatment was significantly more evident in H7 patients, As far as melatonin metabolite results are concerned, data obtained indicate that a phy- — the use of H7-insomnia control device siological day-night difference in melatonin is associated to a higher possibility to obtain concentrations was present in a significantly higher percentage of H7 patients, with respect with our data it is impossible to adscertain a to the placebo group. In addition, the mean val- ue of N/D ratios in the H7 patients reached a — the acupressure device, its assembling higher level, therefore indicating the presence and the instructions included were positively of a normal melatonin rhythm in this group. On evaluated by the majority of patients, mostly the contrary, when the placebo group is con- from the H7 group, with respect to the placebo; sidered, the mean value of night/day ratios was significantly lower than in the H7 group treatment to be stopped, nor adverse local and did not reach the cut-off point of 3, indi- reactions connected to the use of the device cating an insufficient melatonin rhythm.
Therefore, it is plausible to hypothesize that nary data obtained in the present study it is the wrist acupressure device H7-insomnia con- impossible to state that the wrist acupressure trol, although not a pharmaceutical product, might be considered an efficacious tool, with- out adverse effects, that is able to naturally (melatonin metabolite determination before ameliorate sleep quality in insomniacs, at least treatment is lacking), presumably altered in those in which “traditional” pharmacological insomniacs, nevertheless it is possible to therapies (i.e. benzodiazepines) are con- hypothesize that the amelioration of well traindicated. In addition, the hypothesis that being, anxiety level and sleep quality in these the positive effects on insomnia might be medi- ated through an action on melatonin rhythm is nected, at least in part, to the presence of a not jet completely confirmed and therefore Conclusions
Riassunto
Efficacia dell’acupressione esercitata sui polsi duran-te la notte (sul punto HT7) su soggetti con insonnia: obtained in the present study it is possible to Obiettivo. L’insonnia è un problema di vastissima rilevanza che riduce la qualità della vita. Nella sua genesi sono coinvolti molti fattori, associati frequen- L, Parrino L. Studio Morfeo 2: survey on the manage-ment of insomnia by Italian general practitioners. Sleep temente all’ansia, sebbene il meccanismo patogene- tico non sia ancora completamente chiarito. Fra tali fat- 4. Golombek DA, Pevet P, Cardinali DP. Melatonin effects tori, la melatonina e la ritmicità circadiana sembrano on behavior: possibile mediation by the central avere un ruolo importante. Inoltre, è ormai ben noto GABAergic system. Neurosci Biobehav Rev 1996;20:403- che l’acupressione e l’agopuntura sono in grado di migliorare insonnia e ansia, quando applicate su un 5. Shieh KR, Chu YS, Pan JT. Circadian change of dopaminergic neuron activity: effects of constant light punto specifico denominato HT7 Shenmen, localizzato and melatonin. Neurorep 1997;8:2283-7.
a livello del polso. Con tali brevi premesse, scopo 6. Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali del presente studio è stato quello di valutare l’effica- DP, Poeggeler B, Harderland R. Melatonin: Nature’s cia di un sistema per acupressione (H7-insomnia con- most versatile biological signal? Febs J 2006;273:2813- trol), posizionato contemporaneamente sul punto 7. Vandewalle G, Middleton B, Rajaratnam SM, Stone BM, HT7 di entrambi i polsi durante la notte, in termini di Thorleifsdottir B, Arendt J et al. Robust circadian rhythm benessere generale, livello di ansia, qualità del son- in heart rate and its variability: influence of exogenous no e concentrazione urinaria del principale metabo- melatonin and photoperiod. J Sleep Res 2007;16:148- lita della melatonina (6-idrossimelatonina solfato), in 8. Benedetti M, Comba P, Nordio M. Melatonin levels and Metodi. Quaranta pazienti con insonnia sono sta- exposure to electromagnetic fields: biologic back-ground and epidemiological implications. Eur J Oncol ti divisi in due gruppi e ciascun gruppo ha ricevuto il trattamento con H7 o il placebo, secondo una chia- 9. Perras B, Meier M, Dodt C. Light and darkness fail to ve di randomizzazione precedentemente impostata, regulate melatonin release in critically ill humans.
in doppio cieco, per un periodo di 20 notti consecu- tive. Prima e dopo i trattamenti i pazienti hanno rispo- 10. Navara KJ, Nelson RJ. The dark side of light at night: physiological, epidemiological, and ecological conse- sto ad una serie di questionari (General Health quences. J Pineal Res 2007;43:215-24.
Questionnaire 28 items, State Trait Anxiety Inventory, 11. Wyatt JK, Dijk DJ, Ritz-de Cecco A, Ronda JM, Czeisler Pittsburgh Sleep Quality Index) e hanno raccolto i CA. Sleep-facilitating effect of exogenous melatonin campioni di urine, suddivisi in 2 raccolte di 12 ore cia- in healthy young men and women is circadian-phase scuna, per la determinazione del metabolita della 12. Doghramji K. Melatonin and its receptors: a new class of sleep-promoting agents. J Clin Sleep Med 2007;3(5 Risultati. I dati ottenuti indicano che il prodotto H7- insomnia control è maggiormente efficace nel miglio- 13. Wade AG, Ford I, Crawford G, McMahon AD, Nir T, rare la qualità del sonno e ridurre i livelli di ansia nei Laudon M et al. Efficacy of prolonged release melatonin pazienti insonni, rispetto al placebo. Inoltre, il ritmo in insomnia patients aged 55-80 years: quality of sleep del metabolita urinario della melatonina misurato al and next-day alertness outcomes. Curr Med Res Opin2007;23:2597-605. termine del trattamento è risultato essere normale in 14. Sok SR, Erlen JA, Kim KB. Effects of acupuncture ther- un maggior numero di soggetti trattati con H7, rispet- apy on insomnia. J Adv Nurs 2003;44:375-84.
15. Cheuk DKL, Yeung WF, Chung KF, Wong V.
Conclusioni. Sulla base di tali dati è possibile ipo- Acupuncture for insomnia. Cochrane Database of tizzare che il sistema per acupressione H7-insomnia control possa essere considerato uno strumento assai 16. Chan J, Briscomb D, Waterhouse E, Cannaby AM. An uncontrolled pilot study of HT7 for “stress”. Acupunct valido per migliorare in modo naturale la qualità del sonno negli insonni, ancorché privo di effetti indesi- 17. Warren Spence D, Kayumov L, Chen A, Jain U, Katzman derati dal momento che non contiene sostanze far- MA, Shen J et al. Acupuncture increases nocturnal macologiche, il quale agisce tramite un meccanismo melatonin secretion and reduces insomnia and anxiety: non ancora completamente chiarito, ma che potreb- a preliminary report. J Neuropsychiatry Clin Neurosci 18. Park HJ, Chae Y, Jang J, Shim I, Lee H, Lim S. The Parole chiave: Acupressione - Disturbi del sonno - effect of acupuncture on anxiety and neuropeptide Y expression in the basolateral amygdala of maternallyseparated rats. Neurosci Lett 2005;377:179-84.
19. Ebadi M, Govitrapong P, Phansuwan-Pujito P, Nelson F, Reiter RJ. Pineal opioid receptors and analgesic References
action of melatonin. J Pineal Res 1998;24:193-200.
20. Spielberg CD. Anxiety: current trends in theory and 1. Lack LC, Wright HR. Chronobiology of sleep in humans.
research. New York: Academic Press; 1972.
21. Arendt J, Bojkowski C, Franey C, Wright J, Marks V.
2. Wolkove N, Elkholy O, Baltzan M, Palayew M. Sleep Immunoassay of 6-hydroxymelatonin sulphate in and aging:2. Management of sleep disorders in older human plasma and urine: abolition of the urinary 24- hour rhythm with atenolol. J Clin Endocrinol Metab 3. Terzano MG, Cirignotta F, Mondini S, Ferini-Strambi

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