ArticleACS chemical neuroscience2023
Duloxetine and Amitriptyline Reduce Neuropathic Pain by Inhibiting Primary Sensory Input to Spinal Dorsal Horn Neurons via α1- and α2-Adrenergic Receptors.
Article in ACS chemical neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- RETRACTED: Duloxetine, an SNRI, Targets pSTAT3 Signaling:International journal of molecular sciences · 2025Article
- Effects and Mechanisms of Paeoniflorin in Relieving Neuropathic Pain: Network Pharmacological Analysis and Experimental Validation.Neurochemical research · 2025Article
- Monoamine-Uptake Inhibitors and Pain: Antidepressant Drugs Among First-Line Treatments Against Neuropathic Pain and Fibromyalgia.Advances in neurobiology · 2025Review
- Machine learning model for predicting neuropathic pain following thoracic oncology surgery.Frontiers in oncology · 2025Article
- Cryo-EM structure of small-molecule agonist bound delta opioid receptor-GNature communications · 2024Article
- Analgesic Effect of Auricular Vagus Nerve Stimulation on Oxaliplatin-induced Peripheral Neuropathic Pain in a Rodent Model.Experimental neurobiology · 2024Article
- Neuropathic pain in cats: Mechanisms and multimodal management.Journal of feline medicine and surgery · 2024Review
- Constitutive KCC2 Cell- and Synapse-Specifically Regulates NMDA Receptor Activity in the Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Progress in treatment of pathological neuropathic pain after spinal cord injury.Frontiers in neurology · 2024Review
- The analgesic effect of paeoniflorin: A focused review.Open life sciences · 2024Review
- Global Research Trends and Hotspots Analysis of the Scientific Production of Amitriptyline: A Bibliometric Approach.Pharmaceuticals (Basel, Switzerland) · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Antidepressants, such as duloxetine and amitriptyline, are effective for treating patients with chronic neuropathic pain. Inhibiting norepinephrine and serotonin transporters at presynaptic terminals raises extracellular concentrations of norepinephrine. The α1- and α2-adrenergic receptor agonists inhibit glutamatergic input from primary afferent nerves to the spinal dorsal horn. However, the contribution of spinal α1- and α2-adrenergic receptors to the analgesic effect of antidepressants and associated synaptic plasticity remains uncertain. In this study, we showed that systemic administration of duloxetine or amitriptyline acutely reduced tactile allodynia and mechanical and thermal hyperalgesia caused by spinal nerve ligation in rats. In contrast, duloxetine or amitriptyline had no effect on nociception in sham rats. Blocking α1-adrenergic receptors with WB-4101 or α2-adrenergic receptors with yohimbine at the spinal level diminished the analgesic effect of systemically administered duloxetine and amitriptyline. Furthermore, intrathecal injection of duloxetine or amitriptyline similarly attenuated pain hypersensitivity in nerve-injured rats; the analgesic effect was abolished by intrathecal pretreatment with both WB-4101 and yohimbine. In addition, whole-cell patch-clamp recordings in spinal cord slices showed that duloxetine or amitriptyline rapidly inhibited dorsal root-evoked excitatory postsynaptic currents in dorsal horn neurons in nerve-injured rats but had no such effect in sham rats. The inhibitory effect of duloxetine and amitriptyline was abolished by the WB-4101 and yohimbine combination. Therefore, antidepressants attenuate neuropathic pain predominantly by inhibiting primary afferent input to the spinal cord via activating both α1- and α2-adrenergic receptors. This information helps the design of new strategies to improve the treatment of neuropathic pain.
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