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Pharmacopuncture With Scolopendra subspinipes Suppresses Mechanical Allodynia in Oxaliplatin-Induced Neuropathic Mice and Potentiates Clonidine-induced Anti-allodynia Without Hypotension or Motor Impairment

  • Seo-Yeon Yoon
    Affiliations
    Dental Research Institute and Department of Neurobiology and Physiology School of Dentistry
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  • Jeong-Yun Lee
    Affiliations
    Department of Brain and Cognitive Sciences College of Natural Sciences, Seoul National University, Seoul, Republic of Korea
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  • Dae-Hyun Roh
    Affiliations
    Department of Oral Physiology, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
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  • Seog Bae Oh
    Correspondence
    Address reprint requests to Seog Bae Oh, Dental Research Institute and Department of Neurobiology and Physiology School of Dentistry, Department of Brain and Cognitive Sciences College of Natural Sciences, Seoul National University, 28-2 Yeongeon-Dong Chongno-Ku, Seoul 110-749, Republic of Korea.
    Affiliations
    Dental Research Institute and Department of Neurobiology and Physiology School of Dentistry

    Department of Brain and Cognitive Sciences College of Natural Sciences, Seoul National University, Seoul, Republic of Korea
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      Highlights

      • SSP reduces mechanical allodynia in oxaliplatin-induced neuropathic mice
      • SSP-induced anti-allodynic effect is mediated by peripheral nerves at the acupoint.
      • SSP-induced anti-allodynia is mediated by activation of spinal α2-adrenoceptor
      • SSP enhances clonidine-induced anti-allodynia without side effects

      Abstract

      Chemotherapy-induced neuropathic pain is a common dose-limiting side effect of anticancer drugs but lacks an effective treatment strategy. Scolopendra subspinipes has been used in traditional medicine to treat chronic neuronal diseases. Moreover, pharmacopuncture with S subspinipes (SSP) produces potent analgesia in humans and experimental animals. In this study, we examined the effect of SSP into the ST36 acupoint on oxaliplatin-induced mechanical allodynia in mice. Acupoint treatment with SSP (0.5%/20 μL) significantly decreased mechanical allodynia produced by a single oxaliplatin injection (10 mg/ kg i.p.), which was completely prevented by acupoint preinjection of lidocaine. Intrathecal treatment with yohimbine (25 μg/5 μL), an α2-adrenoceptor antagonist, prevented the anti-allodynic effect of SSP. In contrast, a high dose (0.1 mg/ kg i.p.) of clonidine, an α2-adrenoceptor agonist, suppressed oxaliplatin-induced mechanical allodynia but produced severe side effects including hypotension, bradycardia, and motor impairment. The combination of SSP with a lower dose of clonidine (0.03 mg/kg) produced a comparable analgesic effect without side effects. Collectively, our findings demonstrate that SSP produces an analgesic effect in oxaliplatin-induced pain via neuronal conduction at the acupoint and activation of spinal α2-adrenoceptors. Moreover, a combination of low-dose clonidine with SSP represents a novel and safe therapeutic strategy for chemotherapy-induced chronic pain.

      Perspective

      SSP can relieve oxaliplatin-induced mechanical allodynia. Moreover, SSP potentiates clonidine-induced anti-allodynia, allowing a lower dose of clonidine with no significant side effects. The combination of SSP and low-dose clonidine might provide a novel strategy for the management of chemotherapy-induced peripheral neuropathy.

      Key words

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