ArticleKorean journal of anesthesiology2019
Amitriptyline inhibits the MAPK/ERK and CREB pathways and proinflammatory cytokines through A3AR activation in rat neuropathic pain models.
Article in Korean journal of anesthesiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Neuropathic pain in traumatic brain injury: consequences, mechanisms, and therapeutic avenues.Inflammopharmacology · 2026Review
- Modulation of Spinal Mu-Opioid Receptor Expression by Selective Adenosine A1 and A3 Receptor Agonists and Allopurinol in a Rat Model of Neuropathic Pain.Medicina (Kaunas, Lithuania) · 2026Article
- What do ultrasound vocalizations really mean in rats with different origins of pain?Pain reports · 2025Article
- Monoamine-Uptake Inhibitors and Pain: Antidepressant Drugs Among First-Line Treatments Against Neuropathic Pain and Fibromyalgia.Advances in neurobiology · 2025Review
- Unlocking New Therapeutic Options for Vincristine-Induced Neuropathic Pain: The Impact of Preclinical Research.Life (Basel, Switzerland) · 2024Review
- Neuropathic pain, antidepressant drugs, and inflammation: a narrative review.Journal of anesthesia, analgesia and critical care · 2024Review
- Amitriptyline nanoparticle repositioning prolongs the anti-allodynic effect of enhanced microglia targeting.Nanomedicine (London, England) · 2024Article
- Exploring the Biomarkers and Potential Mechanisms of Botulinum Toxin Type A in the Treatment of Microglial Inflammatory Activation through P2X7 Receptors based on Transcriptome Sequencing.Current pharmaceutical design · 2024Article
- In vivo phenotypic validation of adenosine receptor-dependent activity of non-adenosine drugs.Purinergic signalling · 2023Article
- Adenosine signaling mediate pain transmission in the central nervous system.Purinergic signalling · 2023Review
- Characterization of Acetylation of Histone H3 at Lysine 9 in the Trigeminal Ganglion of a Rat Trigeminal Neuralgia Model.Oxidative medicine and cellular longevity · 2022Article
- T lymphocyte and monocyte subsets are dysregulated in type 1 diabetes patients with peripheral neuropathic pain.Brain, behavior, & immunity - health · 2021Article
- Uncovering the Mechanisms of Adenosine Receptor-Mediated Pain Control: Focus on the AInternational journal of molecular sciences · 2021Review
- Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain.International journal of molecular sciences · 2021Article
- Modulation of nociception by amitriptyline hydrochloride in the Speke's hinge-back tortoise (Kiniskys spekii).Veterinary medicine and science · 2021Article
- The neuropsychiatric manifestations of COVID-19: Interactions with psychiatric illness and pharmacological treatment.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Examination and characterisation of the effect of amitriptyline therapy for chronic neuropathic pain on neuropeptide and proteomic constituents of human cerebrospinal fluid.Brain, behavior, & immunity - health · 2021Article
- Adenosine Metabotropic Receptors in Chronic Pain Management.Frontiers in pharmacology · 2021Article
- Targeting Adenosine Receptors: A Potential Pharmacological Avenue for Acute and Chronic Pain.International journal of molecular sciences · 2020Review
- Effect of two-week continuous epidural administration of 2% lidocaine on mechanical allodynia induced by spinal nerve ligation in rats.Anesthesia and pain medicine · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline.
methodsSpinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction.
resultsAmitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline.
conclusionsThe results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.
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