{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T02:19:02Z","timestamp":1781835542488,"version":"3.54.5"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nerve injury can lead to ectopic activation of injured nociceptorsand central sensitization characterized by allodynia and hyperalgesia. Reduction in the activity of primary afferent neurons has been shown to be sufficient in alleviating peripherally generated pain. The cell bodies of such trigeminal nociceptors are located in the trigeminal ganglia (TG) with central processes that terminate in the brainstem trigeminal nucleus caudalis (TNC). The TG is therefore a strategic locus where afferent input can be manipulated. We hypothesized that chemogenetic inhibition of TG would suppress TNC neuronal activity and attenuate pain behaviour in a rat model of painful traumatic trigeminal neuropathy (PTTN).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Trigeminal neuropathic pain was induced in adult male Sprague\u2013Dawley rats (n\u00a0=\u00a024) via chronic constriction injury to the infraorbital nerve (ION\u2010CCI). Na\u00efve and sham rats were used as controls (n\u00a0=\u00a020\/group). Rats within each group received TG\u2010directed microinjections of AAV virus containing either the inhibitory hM4Di\u2010DREADD construct or EGFP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the ION\u2010CCI group, systemic administration of the DREADD agonist clozapine N\u2010oxide (CNO) reversed the hypersensitivity phenotype in animals expressing hM4Di but not EGFP. CNO\u2010mediated activation of hM4Di DREADD in ION\u2010CCI animals was also associated with reduced Fos expression in the TNC elicited by repeated mechanical stimulation of the dermatome ipsilateral to the injury. There was no effect of CNO on pain behaviour or TNC Fos expression in eGFP animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate that DREADDs may offer an effective therapeutic approach for treatment of trigeminal neuropathic pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Trigeminal neuropathic pain is highly resistant to therapy and we are in dire need of novel approaches. This study provides further evidence for the successful application of DREADDs as an effective tool for modulating central nervous system function. CNO mediated activation of hM4Di\u2010DREADDs in the trigeminal ganglion (TG) attenuates nerve injury induced neuropathic pain by acting on hyperactive TG cells. It also establishes the TG as an effective target to manage pain in the face and head. Accessing the TG in clinical populations is a relatively simple and safe procedure, making this approach highly significant. Moreover, the methodology described here has applications in trigeminal neuropathic pain from traumatic other etiologies and in spinal neuropathic pain. Chronic pain syndromes are characterized by a progressive failure of brain centers to adequately inhibit pain and as these are identified, we may be able to target them for therapy. Therefore, our findings might have wide application in chronic pain syndromes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1887","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T16:34:45Z","timestamp":1636734885000},"page":"634-647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Chemogenetic inhibition of trigeminal ganglion neurons attenuates behavioural and neural pain responses in a model of trigeminal neuropathic pain"],"prefix":"10.1002","volume":"26","author":[{"given":"Olga A.","family":"Korczeniewska","sequence":"first","affiliation":[{"name":"Center for Orofacial Pain and Temporomandibular Disorders Department of Diagnostic Sciences Rutgers School of Dental Medicine Rutgers University Newark New Jersey USA"},{"name":"Brain Health Institute Rutgers University Piscataway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan 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