Phenylalanine, acupuncture, and pain control

An experimental study on the enhancing effects of phenylalanine on acupuncture analgesia. Kitade T, Minamikawa M, Nawata T, Shinohara S, Hyodo M, Hosoya E.

In this preliminary study we examined the enhancing effect of D-phenylalanine on acupuncture anesthesia. We made 4 different kinds of experiments with 3 volunteers. The results show that D-phenylalanine extends the analgesic effect of acupuncture analgesia remarkably, with no exception in 3 cases. According to these facts, we believe that these findings have an important meaning for those who are engaged in acupuncture treatment or research.

Am J Chin Med. 1981 Autumn;9(3):243-8.
PMID: 7053024 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/7053024

Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (2nd report)--schedule of administration and clinical effects in low back pain and tooth extraction.Kitade T, Odahara Y, Shinohara S, Ikeuchi T, Sakai T, Morikawa K, Minamikawa M, Toyota S, Kawachi A, Hyodo M, et al. Department of Oriental Medicine, Meiji College of Oriental Medicine, Kyoto, Japan.

D-phenylalanine (DPA) is known to block the activity of carboxypeptidase, an enzyme which degrades enkephalins, endogenous morphine-like substances. Therefore, it is considered that DPA administered as an inhibiting drug of this degrading enzyme might prolong analgesia induced by acupuncture. 1) Thirty patients suffering from chronic low back pain were treated with acupuncture 30 minutes after the oral administration of 4.0 grams of DPA. The results were: excellent in 7 cases, good in 11, fair in 6 and poor in 6. Cases graded excellent and good were then compared with a placebo group. The effect was increased 26% in the DPA-acupuncture group, which shows no statistically significant difference (P less than 0.1). 2) In 56 patients, tooth extraction was performed under acupuncture anesthesia: 18 had received 4.0 gram of DPA (P.O.) 30 minutes earlier. The results were excellent in 8, good in 6, fair in 3, and poor in 1. The excellent and good cases were compared with 38 placebo group cases. The effect in the DPA-acupuncture anesthesia group was significantly increased by 35% (P less than 0.01). 3) In order to determine the optimum time for the administration of DPA, two schedules of administration were compared. [1] DPA was given on the previous day in three 0.5 gram doses (26 cases). [2] A single 4 gram dose was administered 30 minutes before treatment (30 cases). The results from the "excellent", "good" and "fair" cases showed a 16% increase in effectiveness when DPA was administered the day before, not a statistically significant difference (P less than 0.1), but a clear tendency to increase was observed. The above findings show that DPA has an enhancing effect on acupuncture analgesia and anesthesia in clinical practice.

Acupunct Electrother Res. 1990;15(2):121-35.Links
PMID: 1978503 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/1978503?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=2&log$=relatedarticles&logdbfrom=pubmed

Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (first report)--effect on pain threshold and inhibition by naloxone. Kitade T, Odahara Y, Shinohara S, Ikeuchi T, Sakai T, Morikawa K, Minamikawa M, Toyota S, Kawachi A, Hyodo M, et al. Department of Oriental Medicine, Meiji College of Oriental Medicine, Kyoto, Japan.

It has been claimed that the mechanism of acupuncture analgesia can be explained in part by endogenous opioids. If so, it might be possible to enhance the analgesic effect of acupuncture by the administration of endorphins. If D-phenylalanine (DPA), an inhibitor of the endorphin degrading enzyme, is administered, the analgesic effect of acupuncture should be prolonged due to the increased level of endorphins. From the changes of the pain threshold (PT), we investigated whether or not the pre-administration of DPA can enhance the analgesic effect of acupuncture in humans. In addition, we examined the inhibitory effect of naloxone. 1) In all five subjects whose PT was raised after acupuncture anesthesia (respondents), the rise in PT was significantly prolonged by DPA. 2) Out of 10 subjects whose PT remained almost unchanged after acupuncture anesthesia (non-respondents), the PT was increased by DPA in 5 cases. 3) The rise in PT was most prominent when DPA was administered 30 minutes before the start of acupuncture anesthesia. 4) In all 4 respondents in whom the rise in PT persisted after DPA and acupuncture anesthesia, their raised PT dropped after the intravenous injection of naloxone (10 mg). 5) These findings show that DPA enhances the analgesic effect of acupuncture by the "endorphin mechanism."

Acupunct Electrother Res. 1988;13(2-3):87-97.Links
PMID: 2904213 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/2904213

A summary of research on phenylalanine, acupuncture, and pain control

1: Dos Santos JG Jr, Kawano F, Nishida MM, Yamamura Y, Mello LE, Tabosa A.
 Antidepressive-like effects of electroacupuncture in rats.
Physiol Behav. 2008 Jan 28;93(1-2):155-9. Epub 2007 Aug 25.
PMID: 17884111 [PubMed - indexed for MEDLINE]

2: Chen XH, Li Y, Kui Y.
 [Clinical observation on abdominal acupuncture plus Madopa for treatment of
Parkinson's disease]
Zhongguo Zhen Jiu. 2007 Aug;27(8):562-4. Chinese.
PMID: 17853750 [PubMed - indexed for MEDLINE]

3: Chang SL, Tsai CC, Lin JG, Hsieh CL, Lin RT, Cheng JT.
 Involvement of serotonin in the hypoglycemic response to 2 Hz electroacupuncture
of zusanli acupoint (ST36) in rats.
Neurosci Lett. 2005 Apr 29;379(1):69-73. Epub 2005 Jan 20.
PMID: 15814202 [PubMed - indexed for MEDLINE]

4: Sugai GC, Freire Ade O, Tabosa A, Yamamura Y, Tufik S, Mello LE.
 Serotonin involvement in the electroacupuncture- and moxibustion-induced gastric
emptying in rats.
Physiol Behav. 2004 Oct 15;82(5):855-61.
PMID: 15451650 [PubMed - indexed for MEDLINE]

5: Karst M, Scheinichen D, Rueckert T, Wagner T, Wiese B, Piepenbrock S, Fink M.
 Effect of acupuncture on the neutrophil respiratory burst: a placebo-controlled
single-blinded study.
Complement Ther Med. 2003 Mar;11(1):4-10.
PMID: 12667969 [PubMed - indexed for MEDLINE]

6: Russell AL, McCarty MF.
 DL-phenylalanine markedly potentiates opiate analgesia - an example of
nutrient/pharmaceutical up-regulation of the endogenous analgesia system.
Med Hypotheses. 2000 Oct;55(4):283-8. Review.
PMID: 10998643 [PubMed - indexed for MEDLINE]

7: Ceccherelli F, Gagliardi G, Visentin R, Sandona F, Casale R, Giron G.
 The effects of parachlorophenylalanine and naloxone on acupuncture and
electroacupuncture modulation of capsaicin-induced neurogenic edema in the rat
hind paw. A controlled blind study.
Clin Exp Rheumatol. 1999 Nov-Dec;17(6):655-62.
PMID: 10609063 [PubMed - indexed for MEDLINE]

8: Chang CL, Lee JC, Tseng CC, Chang YH, Cheng JT.
 Decrease of anesthetics activity by electroacupuncture on Jen-Chung point in
rabbits.
Neurosci Lett. 1995 Dec 29;202(1-2):93-6.
PMID: 8787839 [PubMed - indexed for MEDLINE]

9: Li G.
 Clinical analysis of Parkinson's disease treated by integration of traditional
Chinese and western medicine.
J Tradit Chin Med. 1995 Sep;15(3):163-9.
PMID: 8569250 [PubMed - indexed for MEDLINE]

10: Kaliuzhnyĭ LV, Kozlov AIu.
 [Action of an enkephalinase blocker on the effect of acupuncture in acupuncture
sensitive and resistant rabbits]
Biull Eksp Biol Med. 1991 Dec;112(12):571-3. Russian.
PMID: 1777610 [PubMed - indexed for MEDLINE]

11: Takeshige C, Mera H, Hisamitsu T, Tanaka M, Hishida F.
 Inhibition of the analgesia inhibitory system by D-phenylalanine and proglumide.
Brain Res Bull. 1991 Mar;26(3):385-91.
PMID: 2049604 [PubMed - indexed for MEDLINE]

12: Sato T, Takeshige C, Shimizu S.
 Morphine analgesia mediated by activation of the acupuncture-analgesia-producing
system.
Acupunct Electrother Res. 1991;16(1-2):13-26.
PMID: 1674831 [PubMed - indexed for MEDLINE]

13: Kitade T, Odahara Y, Shinohara S, Ikeuchi T, Sakai T, Morikawa K, Minamikawa
M, Toyota S, Kawachi A, Hyodo M, et al.
 Studies on the enhanced effect of acupuncture analgesia and acupuncture
anesthesia by D-phenylalanine (2nd report)--schedule of administration and
clinical effects in low back pain and tooth extraction.
Acupunct Electrother Res. 1990;15(2):121-35.
PMID: 1978503 [PubMed - indexed for MEDLINE]

14: Cui R, Ma C, Wang X, Tian Y.
 [The influence of P-chlorophenylalanine on the analgesia of electro-acupuncture
and the level of SP in CNS of rats]
Zhen Ci Yan Jiu. 1990;15(2):109-11. Chinese.
PMID: 1703462 [PubMed - indexed for MEDLINE]

15: Emel'ianenko IV, Bragin EO.
 [The DOPA and dopamine content in the hypothalamus and brain stem of rats with an
experimental stomach ulcer against a background of a course of acupuncture]
Biull Eksp Biol Med. 1989 Mar;107(3):274-9. Russian.
PMID: 2496764 [PubMed - indexed for MEDLINE]

16: Bragin EO, Emel'ianenko IV.
 [Effect of acupuncture on the catecholamine content in the hypothalamus and brain
stem of rats with an experimental stomach ulcer]
Biull Eksp Biol Med. 1989 Feb;107(2):182-4. Russian.
PMID: 2493825 [PubMed - indexed for MEDLINE]

17: Hamba M, Toda K.
 Rat hypothalamic arcuate neuron response in electroacupuncture-induced analgesia.
Brain Res Bull. 1988 Jul;21(1):31-5.
PMID: 2975524 [PubMed - indexed for MEDLINE]

18: Kitade T, Odahara Y, Shinohara S, Ikeuchi T, Sakai T, Morikawa K, Minamikawa
M, Toyota S, Kawachi A, Hyodo M, et al.
 Studies on the enhanced effect of acupuncture analgesia and acupuncture
anesthesia by D-phenylalanine (first report)--effect on pain threshold and
inhibition by naloxone.
Acupunct Electrother Res. 1988;13(2-3):87-97.
PMID: 2904213 [PubMed - indexed for MEDLINE]

19: Markelova VF, Belitskaia RA, Mikhaĭlova AA, Shumova OV.
 [Serotoninergic and catecholaminergic indices in patients with neurotic and
depressive disorders and changes in them as a result of reflexotherapy]
Zh Nevropatol Psikhiatr Im S S Korsakova. 1986;86(11):1708-12. Russian.
PMID: 2433857 [PubMed - indexed for MEDLINE]

20: Yuan H, Han JS.
 [Electroacupuncture accelerates the biogenesis of central enkephalins in the rat]
Sheng Li Xue Bao. 1985 Jun;37(3):265-73. Chinese. No abstract available.
PMID: 3879647 [PubMed - indexed for MEDLINE]

21: Zhang M, Han JS.
 [5-hydroxytryptamine is an important mediator for both high and low frequency
electroacupuncture analgesia]
Zhen Ci Yan Jiu. 1985;10(3):212-5. Chinese. No abstract available.
PMID: 2936534 [PubMed - indexed for MEDLINE]

22: Ehrenpreis S.
 Analgesic properties of enkephalinase inhibitors: animal and human studies.
Prog Clin Biol Res. 1985;192:363-70.
PMID: 2934746 [PubMed - indexed for MEDLINE]

23: Ehrenpreis S.
 Pharmacology of enkephalinase inhibitors: animal and human studies.
Acupunct Electrother Res. 1985;10(3):203-8.
PMID: 2866674 [PubMed - indexed for MEDLINE]

24: Takeshige C.
 Differentiation between acupuncture and non-acupuncture points by association
with analgesia inhibitory system.
Acupunct Electrother Res. 1985;10(3):195-202.
PMID: 2866673 [PubMed - indexed for MEDLINE]

25: Bragin EO, Batueva NN, Durinian RA.
 [Role of the somatic monoaminergic systems in the mechanisms of regulation of
pain sensitivity during reflex stimulation]
Biull Eksp Biol Med. 1983 Oct;96(10):9-12. Russian.
PMID: 6313093 [PubMed - indexed for MEDLINE]

26: Markelova VF, Osipova NN, Belitskaia RA, Gul'iants ER.
 [Effect of reflexotherapy on the functional state of the sympathoadrenal system
in patients with bronchial asthma]
Vopr Med Khim. 1983 Jul-Aug;29(4):106-9. Russian.
PMID: 6623987 [PubMed - indexed for MEDLINE]

27: Iasnetsov VV.
 [Neuropharmacological analysis of electroacupuncture analgesia]
Farmakol Toksikol. 1982 Mar-Apr;45(2):44-8. Russian.
PMID: 6122599 [PubMed - indexed for MEDLINE]

28: Ehrenpreis S.
 D-phenylalanine and other enkephalinase inhibitors as pharmacological agents:
implications for some important therapeutic application.
Subst Alcohol Actions Misuse. 1982;3(4):231-9. No abstract available.
PMID: 6301083 [PubMed - indexed for MEDLINE]

29: Ehrenpreis S.
 D-phenylalanine and other enkephalinase inhibitors as pharmacological agents:
implications for some important therapeutic application.
Acupunct Electrother Res. 1982;7(2-3):157-72.
PMID: 6128872 [PubMed - indexed for MEDLINE]

30: Cheng RS, Pomeranz B.
 Monoaminergic mechanism of electroacupuncture analgesia.
Brain Res. 1981 Jun 29;215(1-2):77-92.
PMID: 6114781 [PubMed - indexed for MEDLINE]

31: Kitade T, Minamikawa M, Nawata T, Shinohara S, Hyodo M, Hosoya E.
 An experimental study on the enhancing effects of phenylalanine on acupuncture
analgesia.
Am J Chin Med. 1981 Autumn;9(3):243-8.
PMID: 7053024 [PubMed - indexed for MEDLINE]

32: Markelova VF, Belitskaia RA, Rudnev SG.
 [Certain mechanisms of the effect of acupuncture on the sympatho-adrenal system
of tobacco smokers]
Zh Nevropatol Psikhiatr Im S S Korsakova. 1981;81(2):117-22. Russian.
PMID: 6785948 [PubMed - indexed for MEDLINE]

33: Cheng RS, Pomeranz B.
 A combined treatment with D-amino acids and electroacupuncture produces a greater
analgesia than either treatment alone; naloxone reverses these effects.
Pain. 1980 Apr;8(2):231-6.
PMID: 7402686 [PubMed - indexed for MEDLINE]

34: Han JS, Tang J, Ren MF, Zhou ZF, Fan SG, Qiu XC.
 Central neurotransmitters and acupuncture analgesia.
Am J Chin Med. 1980 Winter;8(4):331-48.
PMID: 6113756 [PubMed - indexed for MEDLINE]

35: Cheng RS, Pomeranz B.
 Electroacupuncture analgesia could be mediated by at least two pain-relieving
mechanisms; endorphin and non-endorphin systems.
Life Sci. 1979 Dec 3;25(23):1957-62. No abstract available.
PMID: 160969 [PubMed - indexed for MEDLINE]

36: McLennan H, Gilfillan K, Heap Y.
 Some pharmacological observations on the analgesia induced by acupuncture in
rabbits.
Pain. 1977 Jun;3(3):229-38.
PMID: 141645 [PubMed - indexed for MEDLINE]