ArticleProceedings of the National Academy of Sciences of the United States of America2013
Alleviation of chronic pain following rat spinal cord compression injury with multimodal actions of huperzine A.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 66 citations in OpenAlex.
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- Efficient generation of human dorsal spinal GABAergic progenitors for the treatment of spinal cord injury.Experimental & molecular medicine · 2026Article
- Nociceptor α7nAChR activation blunts neuronal HMGB1 release and attenuates inflammation and nociceptive behavior.Molecular medicine (Cambridge, Mass.) · 2025Article
- AMPA receptors play an important role in the biological consequences of spinal cord injury: Implications for AMPA receptor modulators for therapeutic benefit.Biochemical pharmacology · 2024Review
- Natural products in osteoarthritis treatment: bridging basic research to clinical applications.Chinese medicine · 2024Review
- Article
- Transplanting Human Neural Stem Cells with ≈50% Reduction of SOX9 Gene Dosage Promotes Tissue Repair and Functional Recovery from Severe Spinal Cord Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Coexistence of chronic hyperalgesia and multilevel neuroinflammatory responses after experimental SCI: a systematic approach to profiling neuropathic pain.Journal of neuroinflammation · 2022Article
- Spinal Cord Injury Provoked Neuropathic Pain and Spasticity, and Their GABAergic Connection.Neurospine · 2022Article
- Modulation of KIF17/NR2B crosstalk by tozasertib attenuates inflammatory pain in rats.Inflammopharmacology · 2022Article
- Mechanisms of cancer pain.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Emerging Evidence for Intrathecal Management of Neuropathic Pain Following Spinal Cord Injury.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Glial-Neuronal Interactions in Pathogenesis and Treatment of Spinal Cord Injury.International journal of molecular sciences · 2021Review
- Article
- Red-Light (670 nm) Therapy Reduces Mechanical Sensitivity and Neuronal Cell Death, and Alters Glial Responses after Spinal Cord Injury in Rats.Journal of neurotrauma · 2020Article
- Elevated TRPV4 Levels Contribute to Endothelial Damage and Scarring in Experimental Spinal Cord Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Functional Multipotency of Stem Cells and Recovery Neurobiology of Injured Spinal Cords.Cell transplantation · 2019Article
- Alterations in the Timing of Huperzine A Cerebral Pharmacodynamics in the Acute Traumatic Brain Injury Setting.Journal of neurotrauma · 2018Article
- Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Time Course, Behavioral Safety, and Protective Efficacy of Centrally Active Reversible Acetylcholinesterase Inhibitors in Cynomolgus Macaques.Neurochemical research · 2017Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diverse mechanisms including activation of NMDA receptors, microglial activation, reactive astrogliosis, loss of descending inhibition, and spasticity are responsible for ∼40% of cases of intractable neuropathic pain after spinal cord injury (SCI). Because conventional treatments blocking individual mechanisms elicit only short-term effectiveness, a multimodal approach with simultaneous actions against major pain-related pathways may have value for clinical management of chronic pain. We hypothesize that [-]-huperzine A (HUP-A), an alkaloid isolated from the club moss Huperzia serrata, that is a potent reversible inhibitor of acetylcholinesterase and NMDA receptors, could mitigate pain without invoking drug tolerance or dependence by stimulating cholinergic interneurons to impede pain signaling, inhibiting inflammation via microglial cholinergic activation, and blocking NMDA-mediated central hypersensitization. We tested our hypothesis by administering HUP-A i.p. or intrathecally to female Sprague-Dawley rats (200-235 g body weight) after moderate static compression (35 g for 5 min) of T10 spinal cord. Compared with controls, HUP-A treatment demonstrates significant analgesic effects in both regimens. SCI rats manifested no drug tolerance following repeated bolus i.p. or chronic intrathecal HUP-A dosing. The pain-ameliorating effect of HUP-A is cholinergic dependent. Relative to vehicle treatment, HUP-A administration also reduced neural inflammation, retained higher numbers of calcium-impermeable GluR2-containing AMPA receptors, and prevented Homer1a up-regulation in dorsal horn sensory neurons. Therefore, HUP-A may provide safe and effective management for chronic postneurotrauma pain by reestablishing homeostasis of sensory circuits.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.