Kampo Formulae for the Treatment of Neuropathic Pain ∼ Especially the Mechanism of Action of Yokukansan ∼

Sunagawa, Makoto; Takayama, Yasunori; Kato, Mami; Tanaka, Midori; Okumo, Takayuki; Fukuoka, Seiya; Yamaguchi, Kojiro; Tsukada, M.

doi:10.3389/fnmol.2021.705023

Cited by 12 publications

(10 citation statements)

References 133 publications

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“…In clinical practice, traditional Japanese medicines (called Kampo medicines) composed of crude chemicals isolated from plants are prescribed for various purposes such as analgesia along with Western medicines in Japan [320][321][322][323][324][325]. Daikenchuto is one of most frequently prescribed Kampo medicines and is used to treat cold sensation and dysmotility in the abdomen.…”

Section: Actions Of Plant-derived Compounds On Nerve Ap Conductionmentioning

confidence: 99%

Inhibitory Actions of Clinical Analgesics, Analgesic Adjuvants, and Plant-Derived Analgesics on Nerve Action Potential Conduction

Kumamoto

2022

Encyclopedia

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The action potential (AP) conduction in nerve fibers plays a crucial role in transmitting nociceptive information from the periphery to the cerebral cortex. Nerve AP conduction inhibition possibly results in analgesia. It is well-known that many analgesics suppress nerve AP conduction and voltage-dependent sodium and potassium channels that are involved in producing APs. The compound action potential (CAP) recorded from a bundle of nerve fibers is a guide for knowing if analgesics affect nerve AP conduction. This entry mentions the inhibitory effects of clinically used analgesics, analgesic adjuvants, and plant-derived analgesics on fast-conducting CAPs and voltage-dependent sodium and potassium channels. The efficacies of their effects were compared among the compounds, and it was revealed that some of the compounds have similar efficacies in suppressing CAPs. It is suggested that analgesics-induced nerve AP conduction inhibition may contribute to at least a part of their analgesic effects.

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Section: Actions Of Plant-derived Compounds On Nerve Ap Conductionmentioning

confidence: 99%

Inhibitory Actions of Clinical Analgesics, Analgesic Adjuvants, and Plant-Derived Analgesics on Nerve Action Potential Conduction

Kumamoto

2022

Encyclopedia

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“…A recent clinical study on acute postoperative pain after breast cancer surgery also demonstrated the perioperative anxiolytic effects of YKS [ 12 ]. Furthermore, although reviews have described the mechanism of action of YKS in neuropathic and chronic pain [ 13 ], no reports on its action on acute postoperative pain have been presented. However, since YKS has 5-HT 1A receptor agonist activity, we speculated that YKS would also exert an analgesic effect on acute pain, such as postoperative pain.…”

Section: Introductionmentioning

confidence: 99%

Analgesic effects of oral Yokukansan on acute postoperative pain and involvement of the serotonin nervous system: a mouse model study

Kurita,

Sasaki,

Tanaka

et al. 2024

BMC Complement Med Ther

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Background Yokukansan, a traditional Japanese medicine (Kampo), has been widely used to treat neurosis, dementia, and chronic pain. Previous in vitro studies have suggested that Yokukansan acts as a partial agonist of the 5-HT1A receptor, resulting in amelioration of chronic pain through inhibition of nociceptive neuronal activity. However, its effectiveness for treating postoperative pain remains unknown, although its analgesic mechanism of action has been suggested to involve serotonin and glutamatergic neurotransmission. This study aimed to investigate the effect of Yokukansan on postoperative pain in an animal model. Methods A mouse model of postoperative pain was created by plantar incision, and Yokukansan was administered orally the day after paw incision. Pain thresholds for mechanical and heat stimuli were examined in a behavioral experiment. In addition, to clarify the involvement of the serotonergic nervous system, we examined the analgesic effects of Yokukansan in mice that were serotonin-depleted by para-chlorophenylalanine (PCPA) treatment and intrathecal administration of NAN-190, 5-HT1A receptor antagonist. Results Orally administered Yokukansan increased the pain threshold dose-dependent in postoperative pain model mice. Pretreatment of para-chlorophenylalanine dramatically suppressed serotonin immunoreactivity in the spinal dorsal horn without changing the pain threshold after the paw incision. The analgesic effect of Yokukansan tended to be attenuated by para-chlorophenylalanine pretreatment and significantly attenuated by intrathecal administration of 2.5 µg of NAN-190 compared to that in postoperative pain model mice without para-chlorophenylalanine treatment and NAN-190 administration. Conclusion This study demonstrated that oral administration of Yokukansan has acute analgesic effects in postoperative pain model mice. Behavioral experiments using serotonin-depleted mice and mice intrathecally administered with a 5-HT1A receptor antagonist suggested that Yokukansan acts as an agonist at the 5-HT1A receptor, one of the serotonin receptors, to produce analgesia.

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“…Kampo medicine, used in traditional Japanese medicine, has been used to treat a variety of pains, with or without Western medicine ( Arai et al, 2020 ; Sunagawa et al, 2021 ). Yokukansan (YKS; Yi-Gan San in Chinese), which was firstly described in the Bao-ying jin-jing-lu written in 1,550, is a traditional Kampo medicine consisting of seven herbs.…”

Section: Introductionmentioning

confidence: 99%

Yokukansan Inhibits the Development of Morphine Tolerance by Regulating Presynaptic Proteins in DRG Neurons

et al. 2022

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Opioids, such as morphine, are used in clinical settings for the management of acute and chronic pain. However, long-term use of morphine leads to antinociceptive tolerance and hypersensitivity. The cellular and molecular mechanisms of morphine tolerance seem to be quite complex, with suggestions including internalization of the μ-opioid receptor (MOR), neuroinflammation with activation of microglia and astrocytes, and changes in synaptic function in the central nervous system. Yokukansan (YKS), a traditional Kampo medicine consisting of seven herbs, has been used to treat emotional instability, neurosis, and insomnia. Interestingly, recent studies have begun to reveal the inhibitory effect of YKS on the development of morphine tolerance. In the present study, we determined the effect of YKS on morphine tolerance formation and its mechanisms in a rat model, focusing on the synapses between primary sensory neurons and spinal dorsal horn secondary neurons. We found that morphine tolerance formation was significantly inhibited by YKS (0.3 or 1.0 g/kg/day) preadministration for 7 days. Repeated administration of morphine (10 mg/kg/day) increased the expression of presynaptic proteins, including synaptotagmin I, in the spinal cord, which was suppressed by YKS. Furthermore, these changes in presynaptic protein expression were more pronounced at isolectin B4 (IB4)-positive excitatory synapses around the lamina II of the dorsal horn. These results suggest that YKS suppresses the development of morphine tolerance by inhibiting the enhancement of presynaptic function of dorsal root ganglia neurons projecting to spinal dorsal horn neurons caused by continuous morphine administration.

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Kampo Formulae for the Treatment of Neuropathic Pain ∼ Especially the Mechanism of Action of Yokukansan ∼

Cited by 12 publications

References 133 publications

Inhibitory Actions of Clinical Analgesics, Analgesic Adjuvants, and Plant-Derived Analgesics on Nerve Action Potential Conduction

Inhibitory Actions of Clinical Analgesics, Analgesic Adjuvants, and Plant-Derived Analgesics on Nerve Action Potential Conduction

Analgesic effects of oral Yokukansan on acute postoperative pain and involvement of the serotonin nervous system: a mouse model study

Yokukansan Inhibits the Development of Morphine Tolerance by Regulating Presynaptic Proteins in DRG Neurons

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