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Bullatine A stimulates spinal microglial dynorphin A expression to produce anti-hypersensitivity in a variety of rat pain models.
- Source :
-
Journal of Neuroinflammation . 8/30/2016, Vol. 13, p1-18. 18p. - Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao) has been prescribed to manage chronic pain, arthritis, and traumatic injuries. Bullatine A, a C20-diterpenoid alkaloid, is one of its principle effective compounds. This study aimed to investigate the anti-hypersensitivity of bullatine A in a variety of rat pain models and explore its mechanisms of action.<bold>Methods: </bold>Rat neuropathic pain, inflammatory pain, diabetic neuropathic pain, and bone cancer pain models were used. Dynorphin A and pro-inflammatory cytokines were measured in the spinal cord and cultured primary microglia. Double immunofluorescence staining of dynorphin A and glial and neuronal cellular markers was also measured in the spinal cord.<bold>Results: </bold>Subcutaneous and intrathecal injection of bullatine A dose-dependently attenuated spinal nerve ligation-, complete Freud's adjuvant-, diabetes-, and bone cancer-induced mechanical allodynia and thermal hyperalgesia, with the efficacies of 45-70 % inhibition, and half-effective doses of 0.9-1.9 mg/kg for subcutaneous injection. However, bullatine A was not effective in blocking acute nociceptive response in the normal condition. Bullatine A specifically stimulated dynorphin A expression in microglia in the spinal cord in vivo and cultured primary microglia in vitro; the stimulatory effects were completely inhibited by the microglial inhibitor minocycline. In contrast, bullatine A did not have an inhibitory effect on peripheral nerve injury- or lipopolysaccharide-induced pro-inflammatory cytokine expression. The spinal anti-allodynic effects of bullatine A were entirely blocked by intrathecal injection of minocycline, the specific dynorphin A antiserum, and the selective k-opioid receptor antagonist.<bold>Conclusions: </bold>We, for the first time, demonstrate that bullatine A specifically attenuates pain hypersensitivity, regardless of the pain models employed. The results also suggest that stimulation of spinal microglial dynorphin A expression mediates bullatine A anti-nociception in pain hypersensitivity conditions. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PHYSIOLOGICAL effects of alkaloids
*ANIMAL models in research
*PAIN
*BIOCHEMICAL mechanism of action
*DYNORPHINS
*CYTOKINES
*MICROGLIA
*SPINAL cord
*LABORATORY rats
*SUBCUTANEOUS injections
*ALKALOIDS
*ANALGESICS
*ANIMAL experimentation
*ANIMAL populations
*BIOLOGICAL models
*CELL culture
*DOSE-effect relationship in pharmacology
*GENE expression
*HYDROCARBONS
*HYPERALGESIA
*MOLECULAR structure
*NEURALGIA
*OPIOID peptides
*RATS
*PHARMACODYNAMICS
*THERAPEUTICS
THERAPEUTIC use of alkaloids
Subjects
Details
- Language :
- English
- ISSN :
- 17422094
- Volume :
- 13
- Database :
- Academic Search Index
- Journal :
- Journal of Neuroinflammation
- Publication Type :
- Academic Journal
- Accession number :
- 117796846
- Full Text :
- https://doi.org/10.1186/s12974-016-0696-2