ArticleBiological psychiatry2017
Parabrachial Pituitary Adenylate Cyclase-Activating Polypeptide Activation of Amygdala Endosomal Extracellular Signal-Regulated Kinase Signaling Regulates the Emotional Component of Pain.
Article in Biological psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 85 citations in OpenAlex.
- Bed Nucleus of the Stria Terminalis PACAP Signaling in the Dorsal Medial Habenula Mediates Depression-Related Behavioral Responses After Chronic Stress.Biological psychiatry · 2026Article
- Amygdalar calcitonin gene-related peptide driven effects of cold sensitivity induced by peripheral neuropathy in mice.The journal of pain · 2026Article
- β-arrestin1 orchestrates endosomal signaling to regulate translational control of circadian light entrainment.Communications biology · 2026Article
- Parabrachial CGRP Neurons Regulate Opioid Reinforcement.bioRxiv : the preprint server for biology · 2026Article
- Genetic subtraction reveals divergent pathways and targets in anxiety-related and anxiety-independent TMD.The journal of headache and pain · 2026Article
- Brain-cancer interactions outside the CNS.Oncogene · 2026Review
- Mechanisms of the trigeminal-lateral parabrachial-rostroventral medullary circuits involved in experimental occlusal interference induced chronic orofacial pain.The journal of headache and pain · 2026Article
- Effects of electroacupuncture at Zusanli on pain-perception-related brain nuclei in KOA mice: a study on cortical and subcortical c-fos expression.Behavioral and brain functions : BBF · 2026Article
- Recent progress in chronic pain-related negative emotions and cognitive dysfunction: insights into the mechanisms underlying neural circuitry.Frontiers in cellular neuroscience · 2026Review
- Chemogenetic modulation of PAC1-expressing neurons in the bed nucleus of the stria terminalis (BNST) alters anxiety-related behaviors in male mice.Behavioral neuroscience · 2025Article
- Kölliker-Fuse/Parabrachial Complex PACAP-Glutamate Pathway to the Extended Amygdala Couples Rapid Autonomic and Delayed Endocrine Responses to Acute Hypotension.International journal of molecular sciences · 2025Article
- Associations between PACAP levels and psychophysiological indicators of fear and arousal in adults with posttraumatic stress symptoms.Journal of mood and anxiety disorders · 2025Article
- PACAP/PAC1-R activation contributes to hyperalgesia in 6-OHDA-induced Parkinson's disease model rats via promoting excitatory synaptic transmission of spinal dorsal horn neurons.Acta pharmacologica Sinica · 2023Article
- Article
- Pax6 affects Ras-Raf-ERK1/2 in mouse aging brain.Biogerontology · 2023Article
- PACAP Controls Endocrine and Behavioral Stress Responses via Separate Brain Circuits.Biological psychiatry global open science · 2023Article
- Exosome-sheathed ROS-responsive nanogel to improve targeted therapy in perimenopausal depression.Journal of nanobiotechnology · 2023Article
- Young adult and aged female rats are vulnerable to amygdala-dependent, but not hippocampus-dependent, memory impairment following short-term high-fat diet.Brain research bulletin · 2023Review
- Novel Fluorescently Labeled PACAP and VIP Highlight Differences between Peptide Internalization and Receptor Pharmacology.ACS pharmacology & translational science · 2023Article
- Neuropeptides and small-molecule amine transmitters: cooperative signaling in the nervous system.Cellular and molecular life sciences : CMLS · 2022Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundChronic pain and stress-related psychopathologies, such as depression and anxiety-associated abnormalities, are mutually reinforcing; however, the neuronal circuits and mechanisms that underlie this reinforcement are still not well understood. Pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1) and its cognate PAC1 receptor (Adcyap1r1) are expressed in peripheral nociceptive pathways, participate in anxiety-related responses and have been have been linked to posttraumatic stress disorder and other mental health afflictions.
methodsUsing immunocytochemistry, pharmacological treatments and behavioral testing techniques, we have used a rodent partial sciatic nerve chronic constriction injury model (n = 5-8 per group per experiment) to evaluate PACAP plasticity and signaling in nociceptive and stress-related behaviors.
resultsWe show that chronic neuropathic pain increases PACAP expression at multiple tiers along the spinoparabrachioamygdaloid tract. Furthermore, chronic constriction injury bilaterally augments nociceptive amygdala (in the central nucleus of the amygdala [CeA]) PACAP immunoreactivity, extracellular signal-regulated kinase phosphorylation, and c-Fos activation, in parallel with heightened anxiety-like behavior and nociceptive hypersensitivity. Acute CeA infusions with the PACAP receptor antagonist PACAP(6-38) blocked chronic constriction injury-induced behavioral responses. Additionally, pretreatments with inhibitors of mitogen-activated protein kinase enzymes or endocytosis to block endosomal PACAP receptor extracellular signal-regulated kinase signaling attenuated PACAP-induced CeA neuronal activation and nociceptive responses.
conclusionsOur data suggest that chronic pain-induced PACAP neuroplasticity and signaling in spinoparabrachioamygdaloid projections have an impact on CeA stress- and nociception-associated maladaptive responses, which can be ameliorated upon receptor antagonism even during injury progression. Thus, the PACAP pathway provides for an important mechanism underlying the intersection of stress and chronic pain pathways via the amygdala.
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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.