ArticleJournal of neuroinflammation2020
The analgesic action of larixyl acetate, a potent TRPC6 inhibitor, in rat neuropathic pain model induced by spared nerve injury.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Phenotypic Subacute Toxicity Assessment of Intranasally Administered Larixyl Acetate: Implications for Potential Airway Applications.Journal of xenobiotics · 2026Article
- TRPC6-Mediated CaCells · 2026Article
- Breaking Through Cancer Pain: From Single-Drug Management to Multimodal Analgesia.Pain research & management · 2026Review
- Anacyphrethines A and B as potent analgesics: Multiple ion channel inhibitors with an unprecedented chemical architecture.Acta pharmaceutica Sinica. B · 2025Article
- Article
- Spinal TRPC3 promotes neuropathic pain and coordinates phospholipase C-induced mechanical hypersensitivity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Anesthetic- and Analgesic-Related Drugs Modulating Both Voltage-Gated NaBiomolecules · 2024Review
- Transcranial Magneto-Acoustic Stimulation Protects Synaptic Rehabilitation from Amyloid-Beta Plaques via Regulation of Microglial Functions.International journal of molecular sciences · 2024Article
- Effects of NADPH Oxidase Isoform-2 (NOX2) Inhibition on Behavioral Responses and Neuroinflammation in a Mouse Model of Neuropathic Pain.Biomedicines · 2023Article
- Neurodynamic Treatment Promotes Mechanical Pain Modulation in Sensory Neurons and Nerve Regeneration in Rats.Biomedicines · 2022Article
- Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats.Journal of pain research · 2022Article
- Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials.Archives of pharmacal research · 2021Review
- Validation of an LC-MS/MS Method to Quantify the New TRPC6 Inhibitor SH045 (LarixylPharmaceuticals (Basel, Switzerland) · 2021Article
- Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury.Frontiers in cell and developmental biology · 2021Article
- Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications.Frontiers in neuroscience · 2020Review
- TRPC6 Attenuates Cortical Astrocytic Apoptosis and Inflammation in Cerebral Ischemic/Reperfusion Injury.Frontiers in cell and developmental biology · 2020Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNeuropathic pain is a debilitating status that is insusceptible to the existing analgesics. It is important to explore the underlying pathophysiological changes and search for new pharmacological approaches. Transient receptor potential canonical 6 (TRPC6) is a mechanosensitive channel that is expressed by dorsal root ganglia and glial cells. It has been demonstrated that this channel in dorsal root ganglia plays essential roles in the formation of mechanical hyperalgesia in neuropathic pain. Recent pharmacological screening suggests that larixyl acetate (LA), a main constituent of larch resin, is able to selectively inhibit TRPC6 function. But whether LA is effective in treating neuropathic pain remains unknown. We investigated the efficacy of LA in rat neuropathic pain model, examined its effects on central neuroinflammation, and explored the possible molecular mechanisms by targeting the spinal dorsal horn.
methodsSpared nerve injury (SNI) was conducted in Sprague-Dawley rats. Mechanical hypersensitivity and cold allodynia before and after single and multiple i.t. applications of LA at the dose of 3, 10, and 30 μM were evaluated by von Frey filament and acetone tests, respectively. Western blot, immunohistochemical, and immunocytochemical stainings were employed to examine the level and expression feature of ionized calcium-binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), TRPC6, and phosphorylated p38 kinase. The changes of cytokine concentrations, including that of TNF-α, IL-1β, IL-6, and IL-10, were also assessed by multiplex analysis. TRPC6 antisense strategy was finally adopted to investigate the action mechanisms of LA.
resultsSingle application of LA on day 5 post injury caused dose-dependent inhibition of mechanical allodynia with the ED
conclusionsThese data demonstrate that i.t. applied LA exhibits analgesic and anti-inflammatory action in neuropathic pain. The action of LA involves the suppression of TRPC6 and p38 signaling in the microglia. LA may be thus a promising pharmacological candidate for the treatment of intractable chronic pain.
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