ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 papers.
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Who cites it
217 citing papers in PubMed, 416 citations in OpenAlex.
- Effect of a high-fat and high-calorie food on the pharmacokinetics of a novel, potent GABA analog HSK16149 in healthy subjects.Pharmacology research & perspectives · 2023Trial
- Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of Mirogabalin in Healthy Chinese Participants: A Randomized, Double-Blind, Placebo-Controlled Study.Advances in therapy · 2023Trial
- Trial
- Long-term safety and efficacy of mirogabalin in Asian patients with diabetic peripheral neuropathic pain.Journal of diabetes investigation · 2020Trial
- Trial
- Coadministration of probenecid and cimetidine with mirogabalin in healthy subjects: A phase 1, randomized, open-label, drug-drug interaction study.British journal of clinical pharmacology · 2018Trial
- Tolerability, pharmacokinetics, and pharmacodynamics of mirogabalin in healthy subjects: Results from phase 1 studies.Pharmacology research & perspectives · 2018Trial
- Sedative effects of oral pregabalin premedication on intravenous sedation using propofol target-controlled infusion.Journal of anesthesia · 2017Trial
- The CAGE Framework (Calcium-Gated Excitability): From Single Neurotransmitters to Calcium States in the Tumor Microenvironment.International journal of molecular sciences · 2026Review
- Comparative Effectiveness of Pregabalin With Duloxetine Versus Pregabalin With Amitriptyline in Chronic Low Back Pain With Radiculopathy: A Prospective Comparative Study.Health science reports · 2026Article
- Perioperative pregabalin does not alter behavioural or diffuse noxious inhibitory control responses in 2 rat models of chronic pain.Pain reports · 2026Article
- Safety and pharmacokinetics of a novel potent GABA analogue crisugabalin in Chinese subjects with various degrees of renal impairment.British journal of clinical pharmacology · 2026Article
- Long-Term Safety and Efficacy of Crisugabalin for Diabetic Peripheral Neuropathic Pain: A 52-Week, Multicenter, Single-Arm Trial.Journal of diabetes research · 2026Article
- Modulation of ion channels as emerging therapeutic targets in the treatment of diabetic neuropathy.EXCLI journal · 2026Review
- Calcium Channel αPain and therapy · 2025Review
- Review
- Therapeutic Potential of Calcium Channel Blockers in Neuropsychiatric, Endocrine and Pain Disorders.Cells · 2025Review
- Biochemistry and physiology of voltage-gated calcium channel trafficking: a target for gabapentinoid drugs.Open biology · 2025Review
- Mechanism-based nonopioid analgesic targets.The Journal of clinical investigation · 2025Review
- Voltage-Gated Ion Channels in Neuropathic Pain Signaling.Life (Basel, Switzerland) · 2025Review
157 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Neuropathic pain results from damage to the peripheral sensory nervous system, which may have a number of causes. The calcium channel subunit alpha(2)delta-1 is upregulated in dorsal root ganglion (DRG) neurons in several animal models of neuropathic pain, and this is causally related to the onset of allodynia, in which a non-noxious stimulus becomes painful. The therapeutic drugs gabapentin and pregabalin (PGB), which are both alpha(2)delta ligands, have antiallodynic effects, but their mechanism of action has remained elusive. To investigate this, we used an in vivo rat model of neuropathy, unilateral lumbar spinal nerve ligation (SNL), to characterize the distribution of alpha(2)delta-1 in DRG neurons, both at the light- and electron-microscopic level. We found that, on the side of the ligation, alpha(2)delta-1 was increased in the endoplasmic reticulum of DRG somata, in intracellular vesicular structures within their axons, and in the plasma membrane of their presynaptic terminals in superficial layers of the dorsal horn. Chronic PGB treatment of SNL animals, at a dose that alleviated allodynia, markedly reduced the elevation of alpha(2)delta-1 in the spinal cord and ascending axon tracts. In contrast, it had no effect on the upregulation of alpha(2)delta-1 mRNA and protein in DRGs. In vitro, PGB reduced plasma membrane expression of alpha(2)delta-1 without affecting endocytosis. We conclude that the antiallodynic effect of PGB in vivo is associated with impaired anterograde trafficking of alpha(2)delta-1, resulting in its decrease in presynaptic terminals, which would reduce neurotransmitter release and spinal sensitization, an important factor in the maintenance of neuropathic pain.
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Registered trials
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.