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Analgesic Effects of Danggui-Shaoyao-San on Various “Phenotypes” of Nociception and Inflammation in a Formalin Pain Model

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Abstract

Danggui-Shaoyao-San (DSS) is a traditional Chinese medicine, which has long been used for pain treatment and has been demonstrated to possess anti-oxidative, cognitive enhancement, and anti-depressant effects. In the present study, the effects of aqueous extracts of DSS on spontaneous pain behaviors and long-term hyperalgesia were examined to investigate the anti-nociceptive effects and underlying mechanisms. Single pretreatment of DSS dose-dependently reduced spontaneous flinches/licking time in the second, rather than the first, phase after subcutaneous injection of 5 % formalin into one hindpaw, in doses of 2.4 and 9.6 g/kg. DSS also dose-dependently inhibited FOS and cyclooxygenase-2 (COX-2) expression in both superficial and deep layers within the spinal dorsal horn. Further, DSS reduced hypoalgesia in the injected paw from 1 to 3 days and produced anti-hyperalgesic actions in both the injected paw after 3 days and non-injected paw. These data suggest involvement of enhancement of descending pain inhibition by suppression of 5-HTT levels in the spinal dorsal horn and reduction of peripheral long-term inflammation, including paw edema and ulcers. These findings suggest that DSS may be a useful therapeutic agent for short- and long-term inflammation induced pain, through both anti-inflammatory and suppression of central sensitization mechanisms.

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    Authors and Affiliations

    1. Department of Radiology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, 710038, China

      Jun-Bin Yin & Wen Wang

    2. Department of Human Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

      Jun-Bin Yin, Wei Hu, Tan Ding, Ting Zhang, Li-Ying Wang & Wen Wang

    3. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China

      Ke-Cheng Zhou & Jun-Ping Kou

    4. Department of Anesthesiology, Fuzhou General Hospital Affiliated to Fujian Medical University, Fuzhou, 350025, People’s Republic of China

      Huang-Hui Wu

    5. Institute of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

      Tan Ding

    6. Departments of Anesthesiology and Pharmacology, Louisiana State University School of Medicine, New Orleans, LA, 70112, USA

      Alan David Kaye

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    Correspondence to Jun-Ping Kou, Alan David Kaye or Wen Wang.

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    This work was supported by the Natural Science Foundation of China (NO. 81271230), the intramural grant of form Open Project of the State Key Laboratory of Natural Medicines, China Pharmaceutical University (SKLNMKF201214) and the Natural Science Foundation of Shaanxi Province (NO. 2012JM4040).

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    All the authors have viewed and agreed with this submission. The authors declare that they have no competing interests.

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    All experimental procedures received prior approval from the Animal Use and Care Committee for Research and Education of the Fourth Military Medical University (Xi’an, China) and the ethical guidelines to investigate experimental pain in conscious animals.

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    Jun-Bin Yin, Ke-Cheng Zhou, Huang-Hui Wu and Wei Hu contributed equally to this work.

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    Supplementary Figure 1

    Fluorescent photomicrographs show neuron could express FOS, but astrocyte or microglia. (A-A2) Colocalization of NeuN (green) and FOS (red), NeuN can be seen the marker for neurons. (B-B2) Expression of GFAP (green) and FOS (red), GFAP can be seen the marker for astrocytes. (C-C2) Expression of Iba1 (green) and FOS (red), Iba1 can be seen the marker for microglias. Scale bar = 20 μm in C2 (applies A-A2, B-B2, C-C1). (GIF 207 kb)

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    Yin, JB., Zhou, KC., Wu, HH. et al. Analgesic Effects of Danggui-Shaoyao-San on Various “Phenotypes” of Nociception and Inflammation in a Formalin Pain Model. Mol Neurobiol 53, 6835–6848 (2016). https://doi.org/10.1007/s12035-015-9606-3

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