ArticleJournal of pain research2019
Melatonin MT2 receptor agonist IIK-7 produces antinociception by modulation of ROS and suppression of spinal microglial activation in neuropathic pain rats.
Article in Journal of pain research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Targeting Oxidative Stress and Mitochondrial Dysfunction in Diabetic Neuropathy: Mechanisms and Therapeutic Opportunities.Antioxidants (Basel, Switzerland) · 2026Review
- Exploring the Active Ingredients and Core Targets of Erxia Decoction in the Treatment of Sleep Disorder by Integration of Network Pharmacology and Proteomics.Combinatorial chemistry & high throughput screening · 2026Article
- Daflon Enhances Morphine Analgesia and Mitigates Tolerance in a Rat Neuropathic Pain Model.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Comparative Analysis of Melatonin and Polydeoxyribonucleotide: Possible Benefits of Co-Treatment Effects and Potential Synergistic Applicability.International journal of molecular sciences · 2025Review
- Review
- The Melatonin Type 2 Receptor Agonist IIK7 Attenuates and Reverses Morphine Tolerance in Neuropathic Pain Rats Through the Suppression of Neuroinflammation in the Spinal Cord.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Identification of Key Genes and Pathways in Oxaliplatin-Induced Neuropathic Pain Through Bioinformatic Analysis.Journal of pain research · 2024Article
- Teneligliptin Co-Infusion Alleviates Morphine Tolerance by Inhibition of Spinal Microglial Cell Activation in Streptozotocin-Induced Diabetic Rats.Antioxidants (Basel, Switzerland) · 2023Article
- The relationship between anesthesia and melatonin: a review.Frontiers in pharmacology · 2023Review
- Psycho-Neuro-Endocrine-Immunology: A Role for Melatonin in This New Paradigm.Molecules (Basel, Switzerland) · 2022Review
- Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain.Antioxidants (Basel, Switzerland) · 2021Article
- Therapeutic effects of peripherally administrated neural crest stem cells on pain and spinal cord changes after sciatic nerve transection.Stem cell research & therapy · 2021Article
- Inhibition of Different Pain Pathways Attenuates Oxidative Stress in Glial Cells: A Mechanistic View on Neuroprotective Effects of Different Types of Analgesics.Iranian journal of pharmaceutical research : IJPR · 2021Article
- Claudin-5 Affects Endothelial Autophagy in Response to Early Hypoxia.Frontiers in physiology · 2021Article
- Role of Melatonin in the Regulation of Pain.Journal of pain research · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn recent years, several melatonin (MLT) receptor agonists have been approved by FDA for the treatment of sleep disorders and depression. Very few studies have shed light on their efficacy against neuropathic pain (NP). IIK-7 is an MT-2 agonist known to promote sleep. Whether IIK-7 suppresses NP has not been reported, and the signaling profile is unknown.
objectiveTo investigate the effect of melatonin type 2 receptor agonist IIK-7 on partial sciatic nerve transection-induced NP in rats and elucidate the underlying molecular mechanisms.
methodsNP was induced by the PSNT in the left leg of adult male Wistar rats. On post-transection day 7, rats were implanted with intrathecal (i.t) catheter connected to an infusion pump and divided in to four groups: sham-operated/vehicle, PSNT/vehicle, PSNT/0.5 μg/hr IIK-7 and PSNT/0.5 μg IIK-7/1 μg 4-p/hr. To test the MT-2 dependence on IIK-7 activity, the animals were implanted with a single i.t catheter and injected MT-2 antagonist 4-Phenyl-2-propionamidotetralin (4-p) 20 mins prior to IIK-7 injection on day 7 after PSNT. The antinociceptive response was measured using a mechanical paw withdrawal threshold. Activation of microglial cells and the expression of NP-associated proteins in the spinal cord dorsal horn was assessed by immunofluorescence assay (IFA) and Western blotting (WB). Reactive oxygen species (ROS) scavenging ability of IIK-7 was evaluated by using bone marrow-derived macrophages (BMDM).
resultsTreatment with the MT-2 agonist IIK-7 significantly alleviated PSNT-induced mechanical allodynia and glial activation along with the inhibition of P44/42 MAPK, HMGB-1, STAT3, iNOS and casp-3 proteins.
conclusionIIK-7 attenuates NP through the suppression of glial activation and suppression of proteins involved in inflammation and apoptosis. MT-2 receptor agonists may establish a promising and unique therapeutic approach for the treatment of NP.
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