Gastrodin relieved complete Freund's adjuvant-induced spontaneous pain by inhibiting inflammatory response

Ting Sun; Jian Wang; Xiang Li; Yu-Jiao Li; Dan Feng; Wen-Long Shi; Ming-Gao Zhao; Jian-Bo Wang; Yu-Mei Wu

doi:10.1016/j.intimp.2016.10.020

Gastrodin relieved complete Freund's adjuvant-induced spontaneous pain by inhibiting inflammatory response

Int Immunopharmacol. 2016 Dec:41:66-73. doi: 10.1016/j.intimp.2016.10.020. Epub 2016 Nov 3.

Authors

Ting Sun¹, Jian Wang², Xiang Li², Yu-Jiao Li³, Dan Feng⁴, Wen-Long Shi², Ming-Gao Zhao³, Jian-Bo Wang⁵, Yu-Mei Wu⁶

Affiliations

¹ Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi Province 710032, P.R.China; Department of Natural Medicine, Institute of Materia Medica, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi Province 710032, P.R.China.
² Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi Province 710032, P.R.China; Student Brigade, The Fourth Military Medical University, Xi'an, Shaanxi Province 710032, P.R.China.
³ Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi Province 710032, P.R.China.
⁴ Department of Diagnostic Radiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi Province 710032, P.R.China.
⁵ Department of Natural Medicine, Institute of Materia Medica, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi Province 710032, P.R.China. Electronic address: [email protected].
⁶ Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi Province 710032, P.R.China. Electronic address: [email protected].

PMID: 27816787
DOI: 10.1016/j.intimp.2016.10.020

Abstract

The analgesic effects of gastrodin (GAS), an active component derived from the Chinese herb Tian ma (Gastrodia elata Blume), on chronic inflammatory pain of mice and the involved molecular mechanisms were investigated. GAS significantly attenuated mice chronic inflammatory pain induced by hindpaw injection of complete Freund's adjuvant (CFA) and the accompanying anxiety-like behaviors. GAS administration reduced CFA-induced up-regulation of GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, GluN2A- and GluN2B-containing N-methyl-d-aspartate (NMDA) receptors, and Ca²⁺/calmodulin-dependent protein kinase II-alpha (CaMKII-α) in the anterior cingulate cortex (ACC). The GluN2A and GluN2B subunits of NMDA receptors, the GluR1 type of AMPA receptor, and CaMKII-α are key molecules responsible for neuroplasticity involved in chronic pain and the accompanying anxiety. Moreover, GAS administration reduced the activation of astrocyte and microglia and the induction of TNF-α and IL-6 in the ACC of the CFA-injected mice. Therefore, GAS administration relieved chronic pain, exerted anxiolytic effects by regulating neuroplasticity molecules, and attenuated the inflammatory response by reducing the induction of TNF-α and IL-6 in the ACC of the CFA-injected mice.

Keywords: ACC; Anxiety; CFA; Chronic inflammatory pain; Gastrodin; IL-6; Neuroplasticity; TNF-α.

MeSH terms

Analgesics / pharmacology
Analgesics / therapeutic use*
Animals
Anti-Anxiety Agents / pharmacology
Anti-Anxiety Agents / therapeutic use*
Anti-Inflammatory Agents / pharmacology
Anti-Inflammatory Agents / therapeutic use*
Anxiety / drug therapy
Anxiety / metabolism
Astrocytes / drug effects
Astrocytes / metabolism
Benzyl Alcohols / pharmacology
Benzyl Alcohols / therapeutic use*
Calcium-Binding Proteins / metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
Freund's Adjuvant
Glial Fibrillary Acidic Protein / metabolism
Glucosides / pharmacology
Glucosides / therapeutic use*
Gyrus Cinguli / drug effects
Gyrus Cinguli / metabolism
Hot Temperature
Hyperalgesia / chemically induced
Hyperalgesia / drug therapy*
Hyperalgesia / metabolism
Interleukin-6 / metabolism
Male
Mice
Mice, Inbred C57BL
Microfilament Proteins / metabolism
Microglia / drug effects
Microglia / metabolism
Pain / chemically induced
Pain / drug therapy*
Pain / metabolism
Receptors, AMPA / metabolism
Receptors, N-Methyl-D-Aspartate / metabolism
Touch
Tumor Necrosis Factor-alpha / metabolism

Substances

Aif1 protein, mouse
Analgesics
Anti-Anxiety Agents
Anti-Inflammatory Agents
Benzyl Alcohols
Calcium-Binding Proteins
Glial Fibrillary Acidic Protein
Glucosides
Interleukin-6
Microfilament Proteins
NR2B NMDA receptor
Receptors, AMPA
Receptors, N-Methyl-D-Aspartate
Tumor Necrosis Factor-alpha
glial fibrillary astrocytic protein, mouse
interleukin-6, mouse
gastrodin
Freund's Adjuvant
Calcium-Calmodulin-Dependent Protein Kinase Type 2
glutamate receptor ionotropic, AMPA 1
N-methyl D-aspartate receptor subtype 2A