ArticleThe journal of headache and pain2023
PACAP6-38 improves nitroglycerin-induced central sensitization by modulating synaptic plasticity at the trigeminal nucleus caudalis in a male rat model of chronic migraine.
Article in The journal of headache and pain, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- TRPV1‑mediated central sensitisation: Core mechanisms of migraine chronification and novel targeted therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- The effects of physical exercise on inflammation-induced maladaptive neuroplasticity in post-traumatic headache.Neuroscience · 2026Review
- New Directions in Migraine Pathophysiology: The Glymphatic System and PACAP.Life (Basel, Switzerland) · 2026Review
- Review
- A pharmacological rat model of recurrent pelvic pain exhibiting hyperalgesia and depression-like behaviors.iScience · 2026Article
- Breaking the medication overuse headache cycle: from nociplastic pain mechanisms to patient-centered interventions - the Junior Editorial Board vision.The journal of headache and pain · 2026Review
- SP1 recruits TET1 to mediate Kif1a demethylation and synaptic remodeling in a mouse model of chronic migraine.The journal of headache and pain · 2026Article
- Dysregulated autophagy, neural signaling pathways and gut-brain axis in a novel vestibular migraine-like rat model: implications for pathogenesis.The journal of headache and pain · 2025Article
- A novel finding on the sex-dependent role of BDNF and GSK-3beta in the medial prefrontal cortex in pain threshold changes in a rat model of fear conditioning with respect to the effect of extinction and the time period after conditioning.Experimental brain research · 2025Article
- Truncated TrkB: The predominant TrkB isoform in nociceptors.The journal of pain · 2025Article
- Antimicrobial Neuropeptides and Their Receptors: Immunoregulator and Therapeutic Targets for Immune Disorders.Molecules (Basel, Switzerland) · 2025Review
- Deciphering the Pharmacological Mechanisms of Wen-Jing-Zhi-Tong Decoction in Treating Primary Dysmenorrhea by UPLC-Q-Exactive- Orbitrap-MS/MS with GC-MS and Network Pharmacology.Combinatorial chemistry & high throughput screening · 2025Article
- Exploring the efficacy of acupuncture for tension-type headache: a literature review and insights from traditional Chinese medicine.Journal of oral & facial pain and headache · 2024Review
- Pituitary adenylate cyclase-activating polypeptide signalling as a therapeutic target in migraine.Nature reviews. Neurology · 2024Review
- Intranasal administration of recombinant human BDNF as a potential therapy for some primary headaches.The journal of headache and pain · 2024Article
- The role of m6A modification in the risk prediction and Notch1 pathway of Alzheimer's disease.iScience · 2024Article
- Brain-Derived Neurotrophic Factor, Nociception, and Pain.Biomolecules · 2024Review
- From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment.Cells · 2023Review
- Role of Neurotrophins in Orofacial Pain Modulation: A Review of the Latest Discoveries.International journal of molecular sciences · 2023Review
- Retinal connections to migraine.Frontiers in neurologyReview
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
aimsChronic migraine (CM) is a common neurological disorder with complex pathogenesis. Evidence suggests that pituitary adenylate cyclase-activating peptide (PACAP) induces migraine-like attacks and may be potential a new target for migraine treatment, but the therapeutic results of targeting PACAP and its receptors are not uniform. Therefore, the aim of this study was to investigate the regulatory effect of PACAP type I receptor (PAC1R) antagonist, PACAP6-38, on nitroglycerin (NTG)-induced central sensitization in a CM model.
methodsSprague-Dawley (SD) rats received repeated injections of NTG to construct a CM model. Mechanical and thermal thresholds were measured using Von Frey filaments and hot plate tests. C-Fos expression was measured by western blotting and immunofluorescence staining to assess the central sensitization. PACAP6-38 was intracerebrally injected into the trigeminal nucleus caudalis (TNC), and then the changes in c-Fos, the synaptic-associated proteins, phospho-ERK1/2 (p-ERK1/2), phosphorylation of cyclic adenosine monophosphate response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were detected. Transmission electron microscopy (TEM) and Golgi-Cox staining were used to observe the ultrastructure of synapses and dendritic structures of TNC neurons.
resultsThe results showed that PACAP and PAC1R expression were significantly raised in the TNC after repeated NTG injections. Additionally, PACAP6-38 treatment alleviated nociceptive sensitization, inhibited NTG-induced overexpression of c-Fos and synaptic-associated proteins in the TNC of CM rat, restored aberrant synaptic structures. Furthermore, the expression of ERK/CREB/BDNF pathway was depressed by PACAP6-38.
conclusionsOur results demonstrated that abnormal synaptic structure in the TNC of CM, which could be reversed by inhibition of PAC1R via down-regulating the ERK/CREB/BDNF signaling pathway. PACAP6-38 improves NTG-induced central sensitization by regulating synaptic plasticity in the TNC of CM rat, which may provide new insights into the treatments targeting PACAP/PAC1R in migraine.
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