ArticleJournal of neuroinflammation2016
Bullatine A stimulates spinal microglial dynorphin A expression to produce anti-hypersensitivity in a variety of rat pain models.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 56 citations in OpenAlex.
- Article
- Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic pain.Frontiers in immunology · 2025Review
- When the cure turns toxic: a case report on toxic alkaloids identified by public mass spectral databases.Frontiers in medicine · 2025Article
- Analgesic effects of bulleyaconitine A: new advances in research from ion channel targets to clinical translation.Frontiers in pharmacology · 2025Review
- Advancements in Non-Addictive Analgesic Diterpenoid Alkaloid Lappaconitine: A Review.International journal of molecular sciences · 2024Review
- Neuropharmacological Potential of Diterpenoid Alkaloids.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Bullatine A exerts anti-inflammatory effects by inhibiting the ROS/JNK/NF-κB pathway and attenuating systemic inflammatory responses in mice.Pharmaceutical biology · 2022Article
- Upregulation of TLR9 may contribute to activation of microglia and painful diabetic neuropathy via the p38 MAPK pathway in rats.Histology and histopathology · 2022Article
- Curcumin Exerts Antinociceptive Effects in Cancer-Induced Bone Pain via an Endogenous Opioid Mechanism.Frontiers in neuroscience · 2021Article
- Bulleyaconitine A Inhibits Morphine-Induced Withdrawal Symptoms, Conditioned Place Preference, and Locomotor Sensitization Via Microglial Dynorphin A Expression.Frontiers in pharmacology · 2021Article
- The spinal microglial IL-10/β-endorphin pathway accounts for cinobufagin-induced mechanical antiallodynia in bone cancer pain following activation of α7-nicotinic acetylcholine receptors.Journal of neuroinflammation · 2020Article
- Cynandione A Alleviates Neuropathic Pain Through α7-nAChR-Dependent IL-10/β-Endorphin Signaling Complexes.Frontiers in pharmacology · 2020Article
- Bulleyaconitine A Exerts Antianxiety and Antivisceral Hypersensitivity Effects.Frontiers in pharmacology · 2020Article
- Bulleyaconitine A Inhibits Visceral Nociception and Spinal Synaptic Plasticity through Stimulation of Microglial Release of Dynorphin A.Neural plasticity · 2020Article
- Effects of alkaloids on peripheral neuropathic pain: a review.Chinese medicine · 2020Review
- Involvement of d-amino acid oxidase in cerebral ischaemia induced by transient occlusion of the middle cerebral artery in mice.British journal of pharmacology · 2019Article
- Activation of GPR40 produces mechanical antiallodynia via the spinal glial interleukin-10/β-endorphin pathway.Journal of neuroinflammation · 2019Article
- Lappaconitine, a C18-diterpenoid alkaloid, exhibits antihypersensitivity in chronic pain through stimulation of spinal dynorphin A expression.Psychopharmacology · 2018Article
- Recent development in antihyperalgesic effect of phytochemicals: anti-inflammatory and neuro-modulatory actions.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Review
- Autocrine Interleukin-10 Mediates Glucagon-Like Peptide-1 Receptor-Induced Spinal Microglial β-Endorphin Expression.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAconiti 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.
methodsRat 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.
resultsSubcutaneous 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.
conclusionsWe, 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.
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