ArticleNeuroscience2011
Activating transcription factor 4, a mediator of the integrated stress response, is increased in the dorsal root ganglia following painful facet joint distraction.
Article in Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- Subfailure capsule strain as the cause of cervical zygapophysial joint pain after whiplash: a scoping review.Pain medicine (Malden, Mass.) · 2026Article
- Unidirectional Crosstalk Between NTRK1 and IGF2 Drives ER Stress in Chronic Pain.Biomedicines · 2025Article
- SARS-CoV-2 airway infection results in the development of somatosensory abnormalities in a hamster model.Science signaling · 2023Article
- SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model.bioRxiv : the preprint server for biology · 2022Article
- ATF4 selectively regulates heat nociception and contributes to kinesin-mediated TRPM3 trafficking.Nature communications · 2021Article
- Physiologic facet capsule stretch can induce pain & upregulate matrix metalloproteinase-3 in the dorsal root ganglia when preceded by a physiological mechanical or nonpainful chemical exposure.Clinical biomechanics (Bristol, Avon) · 2019Article
- Repeated High Rate Facet Capsular Stretch at Strains That are Below the Pain Threshold Induces Pain and Spinal Inflammation With Decreased Ligament Strength in the Rat.Journal of biomechanical engineering · 2018Article
- Ablation of IB4 non-peptidergic afferents in the rat facet joint prevents injury-induced pain and thalamic hyperexcitability via supraspinal glutamate transporters.Neuroscience letters · 2017Article
- eIF2α phosphorylation controls thermal nociception.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Tissue Strain Reorganizes Collagen With a Switchlike Response That Regulates Neuronal Extracellular Signal-Regulated Kinase Phosphorylation In Vitro: Implications for Ligamentous Injury and Mechanotransduction.Journal of biomechanical engineering · 2016Article
- Pain from intra-articular NGF or joint injury in the rat requires contributions from peptidergic joint afferents.Neuroscience letters · 2015Article
- Involvement of endoplasmic reticulum stress response in orofacial inflammatory pain.Experimental neurobiology · 2014Article
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- Ketorolac reduces spinal astrocytic activation and PAR1 expression associated with attenuation of pain after facet joint injury.Journal of neurotrauma · 2013Article
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- Whiplash-like facet joint loading initiates glutamatergic responses in the DRG and spinal cord associated with behavioral hypersensitivity.Brain research · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Chronic neck pain is one of the most common musculoskeletal disorders in the US. Although biomechanical and clinical studies have implicated the facet joint as a primary source of neck pain, specific cellular mechanisms still remain speculative. The purpose of this study was to investigate whether a mediator (activating transcription factor; 4ATF4) of the integrated stress response (ISR) is involved in facet-mediated pain. Holtzman rats underwent C6/C7 facet joint loading that produces either painful (n=16) or nonpainful (n=8) responses. A sham group (n=9) was also included as surgical controls. Behavioral sensitivity was measured and the C6 dorsal root ganglia (DRGs) were harvested on day 7 to evaluate the total and neuronal ATF4 expression. In separate groups, an intra-articular ketorolac injection was administered either immediately (D0 ketorolac) or 1 day (D1 ketorolac) after painful facet joint loading. Allodynia was measured at days 1 and 7 after injury to assess the effects on behavioral responses. ATF4 and BiP (an indicator of ISR activation) were separately quantified at day 7. Facet joint loading sufficient to elicit behavioral hypersensitivity produced a threefold increase in total and neuronal ATF4 expression in the DRG. After ketorolac treatment at the time of injury, ATF4 expression was significantly (P<0.01) reduced despite not producing any attenuation of behavioral responses. Interestingly, ketorolac treatment at day 1 significantly (P<0.001) alleviated behavioral sensitivity at day 7, but did not modify ATF4 expression. BiP expression was unchanged after either intervention time. Results suggest that ATF4-dependent activation of the ISR does not directly contribute to persistent pain, but it may sensitize neurons responsible for pain initiation. These behavioral and immunohistochemical findings imply that facet-mediated pain may be sustained through other pathways of the ISR.
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