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Lemairamin, isolated from the Zanthoxylum plants, alleviates pain hypersensitivity via spinal α7 nicotinic acetylcholine receptors
- Source :
- Biochemical and Biophysical Research Communications. 525:1087-1094
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Lemairamin (also known as wgx-50), is isolated from the pericarps of the Zanthoxylum plants. As an agonist of α7 nicotinic acetylcholine receptors (α7nAChRs), it can reduce neuroinflammation in Alzheimer's disease. This study evaluated its antinociceptive effects in pain hypersensitivity and explored the underlying mechanisms. The data showed that subcutaneous lemairamin injection dose-dependently inhibited formalin-induced tonic pain but not acute nociception in mice and rats, while intrathecal lemairamin injection also dose-dependently produced mechanical antiallodynia in the ipsilateral hindpaws of neuropathic and bone cancer pain rats without affecting mechanical thresholds in the contralateral hindpaws. Multiple bi-daily lemairamin injections for 7 days did not induce mechanical antiallodynic tolerance in neuropathic rats. Moreover, the antinociceptive effects of lemairamin in formalin-induced tonic pain and mechanical antiallodynia in neuropathic pain were suppressed by the α7nAChR antagonist methyllycaconitine. In an α7nAChR antagonist-reversible manner, intrathecal lemairamin also stimulated spinal expression of IL-10 and β-endorphin, while lemairamin treatment induced IL-10 and β-endorphin expression in primary spinal microglial cells. In addition, intrathecal injection of a microglial activation inhibitor minocycline, anti-IL-10 antibody, anti-β-endorphin antiserum or μ-opioid receptor-preferred antagonist naloxone was all able to block lemairamin-induced mechanical antiallodynia in neuropathic pain. These data demonstrated that lemairamin could produce antinociception in pain hypersensitivity through the spinal IL-10/β-endorphin pathway following α7nAChR activation.
- Subjects :
- Male
Zanthoxylum
0301 basic medicine
Agonist
alpha7 Nicotinic Acetylcholine Receptor
medicine.drug_class
Aconitine
Biophysics
Minocycline
Pharmacology
Biochemistry
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Formaldehyde
Animals
Medicine
Rats, Wistar
Molecular Biology
Injections, Spinal
Neuroinflammation
Methyllycaconitine
Acrylamides
Analgesics
Naloxone
business.industry
beta-Endorphin
Antagonist
Cancer Pain
Cell Biology
Interleukin-10
Rats
Interleukin 10
030104 developmental biology
Nociception
Spinal Cord
chemistry
Hyperalgesia
030220 oncology & carcinogenesis
Neuropathic pain
Neuralgia
Female
Microglia
business
medicine.drug
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 525
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....f9913b7296eeba5a7ebb57fd26ad00f0