{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:31:40Z","timestamp":1787243500170,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:00:00Z","timestamp":1717113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["NIH-AR047410"],"award-info":[{"award-number":["NIH-AR047410"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glutamate functions as the major excitatory neurotransmitter for primary sensory neurons and has a crucial role in sensitizing peripheral nociceptor terminals producing sensitization. Glutaminase (GLS) is the synthetic enzyme that converts glutamine to glutamate. GLS-immunoreactivity (-ir) and enzyme activity are elevated in dorsal root ganglion (DRG) neuronal cell bodies during chronic peripheral inflammation, but the mechanism for this GLS elevation is yet to be fully characterized. It has been well established that, after nerve growth factor (NGF) binds to its high-affinity receptor tropomyosin receptor kinase A (TrkA), a retrograde signaling endosome is formed. This endosome contains the late endosomal marker Rab7GTPase and is retrogradely transported via axons to the cell soma located in the DRG. This complex is responsible for regulating the transcription of several critical nociceptive genes. Here, we show that this retrograde NGF signaling mediates the expression of GLS in DRG neurons during the process of peripheral inflammation. We disrupted the normal NGF\/TrkA signaling in adjuvant-induced arthritic (AIA) Sprague Dawley rats by the pharmacological inhibition of TrkA or blockade of Rab7GTPase, which significantly attenuated the expression of GLS in DRG cell bodies. The results indicate that NGF\/TrkA signaling is crucial for the production of glutamate and has a vital role in the development of neurogenic inflammation. In addition, our pain behavioral data suggest that Rab7GTPase can be a potential target for attenuating peripheral inflammatory pain.<\/jats:p>","DOI":"10.3390\/ijms25116053","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T03:46:49Z","timestamp":1717127209000},"page":"6053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Nerve Growth Factor Signaling Modulates the Expression of Glutaminase in Dorsal Root Ganglion Neurons during Peripheral Inflammation"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0717-2054","authenticated-orcid":false,"given":"Vikramsingh","family":"Gujar","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, Oklahoma State University, Center for Health Sciences, Tulsa, OK 74107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhika D.","family":"Pande","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Oklahoma State University, Center for Health Sciences, Tulsa, OK 74107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3033-7811","authenticated-orcid":false,"given":"Bhalchandra M.","family":"Hardas","sequence":"additional","affiliation":[{"name":"Department of Electronics Engineering, Shri Ramdeobaba College of Engineering and Management, Nagpur 440013, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8829-926X","authenticated-orcid":false,"given":"Subhas","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Oklahoma State University, Center for Health Sciences, Tulsa, OK 74107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"key":"ref_1","first-page":"321","article-title":"Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo","volume":"116","author":"Hamburger","year":"1951","journal-title":"J. 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