Changes in Blood Fluidity Caused by Electroacupuncture Stimulation

Tadashi Hisamitsu,Shintaro Ishikawa 사단법인약침학회 2014 Journal of Acupuncture & Meridian Studies Vol.7 No.4

In Oriental medicine, the state of blood stagnation is called “Oketsu,” meaning preceding state or symptomatic of sickness. Acupuncture stimulation is often used clinically for the treatment of “Oketsu.” The degree of “Oketsu” is indicated by tongue color and form, swelling, paroxysmal blushing, and dark circles under the eyes. The blood’s fluidity is generally thought to be a blood stagnation factor. “Oketsu” is now considered as physio- logical blood flow and is studied from the perspective of the blood’s fluidity and vascular resistance. In our preliminary research, acupuncture stimuli were very effective in treat- ing conditions associated with a decrease in the fluidity of the blood, such as “Oketsu.” In this review, we discuss recent progress in acupuncture therapy and report mechanisms of its action; we then focus on our original findings on these topics. Furthermore, we pro- pose new factors related to acupuncture stimuli, including the blood’s fluidity, and report our investigations, using the restraint stress method, on the mechanisms underlying acupuncture stimuli.

Influence of moxibustion on collagen-induced arthritis in mice

Tadashi Hisamitsu 대한약침학회 2000 Journal of pharmacopuncture Vol.3 No.2

The influence of moxibustion, a traditional Chinese medical treatment, on type II collagen-induced arthritis (CIA) was examined in DBA/1J mice in vivo. Mice were immunized intradermally twice at the 3-week interval with bovine type II collagen (C Il). The main incidence of arthritis started about on day 30 and lasted to day 60 after the first immunization. Moxibustion with three different regimens, was applied at the acupoint equivalent to GV 4 every other day. Moxibustion, from day 0 to day 30 after the first immunization, suppressed the onset and development of arthritis, as well as anti-collagen antibody level. Treatment with moxibustion, from the day 31 to day 60, also resulted in a significant inhibition of progression of arthritis and production of anti-C II antibody. Thirdly we examined the influence of moxibustion on the established arthritis. Moxibustion given from day 61 to day 120, significantly but mildly decreased the anti-C II antibody level in diseased mice, while the bone erosion and joint destruction were not affected. These results indicate that moxibustion could prevent the incidence and attenuates the development of murine CIA

Inhibitory Effect of Electroacupuncture on Murine Collagen Arthritis and its Possible Mechanisms

Tadashi Hisamitsu 대한약침학회 2001 Journal of pharmacopuncture Vol.4 No.1

The influence of electroacupuncture (EA), a traditional Chinese medical treatment, on type Ⅱ collagen-induced arthritis (CIA) was examined in DBA/1J mice in vivo. Mice were immunized intradermally twice at the 3-week interval with bovine type Ⅱ collagen(C Ⅱ). EA stimulation, begun on the 21 simultaneously with the second immunization, was applied at the acupoint equivalent to GV4 three times a week for 3 weeks. The results showed that EA delayed the onset, attenuated the severity of arthritis, and reduced the anti-collagen antibody level. Furthermore, we investigated the impact of EA on the productions of endogenous interleukin-1 β (IL-1 beta) and prostaglandin E2 (PGE2), and the levels of IL-1 beta mRNA in splenocytes and synovial tissues from C Ⅱ immunized mice on the 45 and cyclooxygenase-2 (COX-2) mRNA in lipopolysaccharide (LPS)-stimulated macrophages of normal mice by using reverse transcriptase-polymerase chain reaction (RT-PCR). EA stimulation significant inhibited the concentrations of splenic endogenous IL-1 beta and serum PGE2. The expression of IL-1 beta mRNA in spleen cells was obviously down-regulated and that in synovial tissues was modestly affected by EA. COX-2 mRNA was highly expressed in cultured peritoneal macrophages when stimulated with LPS. Previous treatment with EA also reduced LPS-stimulated induction of COX-2 mRNA. These data suggest that EA has an inhibitory effect on murine CIA, and the partial mechanism of its therapeutic result may be attributed to inhibiting the productions of IL-1 beta and PGE2 by suppression the IL-1 beta and COX-2 gene activations.

Influence of moxibustion on collagen-induced arthritis in mice

Fang, Jian-Qiao,Aoki, Eri,Seto, Akira,Yu, Ying,Kasahara, Takako,Hisamitsu, Tadashi KOREAN PHARMACOPUNCTURE INSTITUTE 2000 Journal of pharmacopuncture Vol.3 No.2

The influence of moxibustion, a traditional Chinese medical treatment, on type II collagen-induced arthritis (CIA) was examined in DBA/1J mice in vivo. Mice were immunized intradermally twice at the 3-week interval with bovine type II collagen (C Il). The main incidence of arthritis started about on day 30 and lasted to day 60 after the first immunization. Moxibustion with three different regimens, was applied at the acupoint equivalent to GV 4 every other day. Moxibustion, from day 0 to day 30 after the first immunization, suppressed the onset and development of arthritis, as well as anti-collagen antibody level. Treatment with moxibustion, from the day 31 to day 60, also resulted in a significant inhibition of progression of arthritis and production of anti-C II antibody. Thirdly we examined the influence of moxibustion on the established arthritis. Moxibustion given from day 61 to day 120, significantly but mildly decreased the anti-C II antibody level in diseased mice, while the bone erosion and joint destruction were not affected. These results indicate that moxibustion could prevent the incidence and attenuates the development of murine CIA.

Inhibitory Effect of Electroacupuncture on Murine Collagen Arthritis and its Possible Mechanisms

Fang, Jian-Qiao,Aoki, Eri,Yu, Ying,Sohma, Toshimitsu,Kasahara, Takako,Hisamitsu, Tadashi KOREAN PHARMACOPUNCTURE INSTITUTE 2001 Journal of pharmacopuncture Vol.4 No.1

The influence of electroacupuncture (EA), a traditional Chinese medical treatment, on type Ⅱ collagen-induced arthritis (CIA) was examined in DBA/1J mice in vivo. Mice were immunized intradermally twice at the 3-week interval with bovine type Ⅱ collagen(C Ⅱ). EA stimulation, begun on the 21 simultaneously with the second immunization, was applied at the acupoint equivalent to GV4 three times a week for 3 weeks. The results showed that EA delayed the onset, attenuated the severity of arthritis, and reduced the anti-collagen antibody level. Furthermore, we investigated the impact of EA on the productions of endogenous $interleukin-1{\Beta}$ (IL-1 beta) and prostaglandin E2 (PGE2), and the levels of IL-1 beta mRNA in splenocytes and synovial tissues from C Ⅱ immunized mice on the 45 and cyclooxygenase-2 (COX-2) mRNA in lipopolysaccharide (LPS)-stimulated macrophages of normal mice by using reverse transcriptase-polymerase chain reaction (RT-PCR). EA stimulation significant inhibited the concentrations of splenic endogenous IL-1 beta and serum PGE2. The expression of IL-1 beta mRNA in spleen cells was obviously down-regulated and that in synovial tissues was modestly affected by EA. COX-2 mRNA was highly expressed in cultured peritoneal macrophages when stimulated with LPS. Previous treatment with EA also reduced LPS-stimulated induction of COX-2 mRNA. These data suggest that EA has an inhibitory effect on murine CIA, and the partial mechanism of its therapeutic result may be attributed to inhibiting the productions of IL-1 beta and PGE2 by suppression the IL-1 beta and COX-2 gene activations.

Blood Fluidity Enhancement by Electrical Acupuncture Stimulation is Related to an Adrenergic Mechanism

Shintaro Ishikawa,Hiroki Suga,Masaya Fukushima,Atsuhiro Yoshida,Yuri Yoshida,Masataka Sunagawa,Tadashi Hisamitsu 사단법인약침학회 2012 Journal of Acupuncture & Meridian Studies Vol.5 No.1

We have reported that electrical acupuncture stimulation (ACU) increases blood fluidity by decreasing platelet aggregation. In this study, we investigated the mechanism causing the increase of blood fluidity. The effects of ACU on blood fluidity and platelet adhesion were examined using a Micro Channel Array Flow Analyzer (MC-FAN) and a laser scattering platelet aggregometer (PA-20). Male Wistar rats (7e8 weeks old) were used in the study. ACU (1 or 100 Hz, 3e5 V),which causes slight muscle twitching, was applied to the ZuSanli (ST-36) acupoint for 15 or 60 minutes once/day. Blood samples were collected from the inferior vena cava. ACU applied to ST-36 revealed significant increases in blood fluidity, while platelet adhesion activity decreased, regardless of the difference of stimulus time. The acupuncture had an immediate effect. Even if naloxone was administered during acupuncture stimulus, the blood flow time shortened in a similar way, as in the only acupuncture stimulus group. In addition, the effect of acupuncture on blood fluidity was inhibited by a b-antagonist. The results indicate that ACU affects blood fluidity depending on the acupoints, and that the effect of ACU might involve an endogenous adrenergic mechanism.

Promotion of Blood Fluidity by Inhibition of Platelet Adhesion Using Electroacupuncture Stimulation

Shintaro Ishikawa,Makoto Murai,Takao Sato,Masataka Sunagawa,Erika Tokita,Steven K.H. Aung,Kazuhito Asano,Tadashi Hisamitsu 사단법인약침학회 2011 Journal of Acupuncture & Meridian Studies Vol.4 No.1

Stress applied to rats is known to result in a quick decrease in blood fluidity. Although electrical acupuncture stimulation (ACU) attenuates stress responses,the influence of ACU on blood fluidity has not been well examined. In the present study, the effect of ACU on blood fluidity and platelet adhesion was examined using a Micro Channel Array Flow Analyzer and a laser scattering platelet aggregometer (PA-20), respectively. Male Wistar rats (7−8 weeks old) were used. ACU (1 Hz, 3−5 V),which causes slight muscle twitching, was applied to acupoints for 60 minutes/day once or on 2 consecutive days. Stimulated acupoints were as follows: ZuSanli (ST-36), Sanyinjiao (SP-6), Hegu (L-I4), Neiguan (P-6), and Shenshu (BL-23). ACU applied to ST-36, SP-6, and L-14 revealed significant increases in blood fluidity while platelet adhesion activity decreased. No significant changes were observed when ACU was applied to P-6 and BL-23. Results indicate that ACU affects blood fluidity depending on the acupoints. Blood fluidity changed with ACU within 1 day. In other words, the effect of acupuncture has an immediate effect. In addition, platelet aggregation decreased with ACU, suggesting that an increase in blood fluidity is associated with platelet aggregation ability.

Yokukansan (Kampo medicinal formula) prevents the development of morphine tolerance by inhibiting the secretion of orexin A

Ayami Katayama,Yasuaki Kanada,Mana Tsukada,Yuko Akanuma,Haruka Takemura,Takahiro Ono,Hiroki Suga,Hitoshi Mera,Tadashi Hisamitsu,Masataka Sunagawa 한국한의학연구원 2018 Integrative Medicine Research Vol.7 No.2

Background: Yokukansan (YKS), a traditional herbal (Kampo) medicine consisting of seven herbs, is effective in the treatment of pain disorders, such as headache, postherpetic neuralgia, fibromyalgia, and trigeminal neuralgia, and we have previously shown it to be effective against morphine analgesic tolerance in rats. It has been reported that orexin receptor antagonists prevent the development of morphine tolerance and that YKS inhibits the secretion of orexin A in the hypothalamus. This study examined whether the inhibition of the secretion of orexin A by YKS is one mechanism underlying its effect against morphine analgesic tolerance. Methods: Male Wistar rats were administered a subcutaneous injection of morphine hydrochloride (10 mg/kg/day) for 5 days. One group was preadministered YKS, starting 3 days before the morphine. The withdrawal latency following thermal stimulation was measured daily using a hot plate test. On day 5, the levels of orexin A in the plasma and the midbrain were measured, and the appearance of activated astrocytes in the midbrain was examined by immunofluorescence staining. Results: The preadministration of YKS prevented the development of morphine tolerance. The repeated administration of morphine significantly increased the plasma and midbrain levels of orexin A and the activation of astrocytes. These increases were significantly inhibited by the preadministration of YKS. Conclusion: These results suggest that the preadministration of YKS attenuated the development of antinociceptive morphine tolerance and that the inhibition of orexin A secretion may be one mechanism underlying this phenomenon.

Moxibustion at Mingmen Reduces Inflammation and Decreases IL-6 in a Collagen-Induced Arthritis Mouse Model

Morihiro Kogure,Naomi Mimura,Hideshi Ikemoto,Shintaro Ishikawa,Takako Nakanishi-Ueda,Masataka Sunagawa,Tadashi Hisamitsu 사단법인약침학회 2012 Journal of Acupuncture & Meridian Studies Vol.5 No.1

The purpose of this study was to compare the effectiveness of moxibustion (MOX) treatment at the GV4 and CV12 acupoints, and to determine the correlations between MOX treatment and interleukin (IL)-6 and corticosterone levels in a collagen-induced arthritis (CIA) mouse model. CIA mice were immunized twice intradermally over a 3-week interval with bovine type II collagen. After the second immunization (day 21), MOX was applied to the mouse equivalent of the GV4 and CV12 acupoints with a 1 mg moxa cone five times/day. Clinical symptoms of CIA were observed three times/week until day 35. The concentrations of IL-6 and corticosterone in the blood samples were measured by immunoassay kits. At day 35, the incidence of CIA was significantly decreased in mice treated with MOX at the GV4 acupoint (78%, nZ23, p < 0.05), compared to untreated CIA mice (100%) and mice treated with MOX at the CV12 acupoint (100%). IL-6 and corticosterone levels were significantly increased by immunization. IL-6 levels significantly decreased in mice treated with MOX at the GV4 acupoint. These results suggest that MOX treatment suppressed CIA at the GV4 acupoint, not at the CV12 acupoint, possibly through inhibition of IL-6 production.

Yokukansan, a Kampo medicine, prevents the development of morphine tolerance through the inhibition of spinal glial cell activation in rats

Mariko Takemoto,Masataka Sunagawa,Mayumi Okada,Hideshi Ikemoto,Hiroki Suga,Ayami Katayama,Hiroshi Otake,Tadashi Hisamitsu 한국한의학연구원 2016 Integrative Medicine Research Vol.5 No.1

Background Animal models have shown that glial cells (microglia and astrocytes) in the spinal cord undergo activation following peripheral injury associated with chronic pain, suggesting the involvement of these cells in pain diseases. We have previously reported that Yokukansan (YKS), a Japanese traditional herbal (Kampo) medicine, is effective against chronic pain through the suppression of spinal glial cell activation. Morphine is a widely-used opioid analgesic for relieving severe pain, but its repeated administration leads to the development of antinociceptive tolerance. The development of morphine tolerance is also reported to be caused by spinal glial cells activation. In the present study, we investigated the inhibitory effects of YKS on the development of morphine tolerance and the activation of the spinal microglia and astrocytes using a rat model. Methods Male Wistar rats received a subcutaneous injection of morphine hydrochloride (10 mg/kg/d) for 7 days, and the withdrawal latency to thermal stimulation was measured daily using a hot plate test. Thereafter, the appearance of activated microglia and astrocyte in the spinal cord (L5) was examined by immunofluorescence staining. Ionized calcium binding adapter molecule-1 (Iba-1) staining was used to label microglia and glial fibrillary acidic protein (GFAP) staining was performed to label astrocytes. YKS was administered mixed with powdered rodent chow at a concentration of 3%. Results The preadministration of YKS (started 3 d before the morphine injection) prevented the development of morphine tolerance. The repeated administration of morphine increased Iba-1 and GFAP immune reactivities in the spinal cord; however, these activations were inhibited by the preadministration of YKS. Conclusion These results suggest that the preadministration of YKS attenuates the development of antinociceptive morphine tolerance, and the suppression of spinal glial cell activation may be one mechanism underlying this phenomenon.