{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:02:19Z","timestamp":1781848939684,"version":"3.54.5"},"reference-count":90,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Veterans Affairs BLRD Merit Review Award","award":["1I01 BX002695-06"],"award-info":[{"award-number":["1I01 BX002695-06"]}]},{"name":"VA Drug Discovery","award":["BX005937-01A1"],"award-info":[{"award-number":["BX005937-01A1"]}]},{"name":"Department of Defense Chronic Pain Management Research Program, Investigator-Initiated Research Award","award":["CPMRP W81XWH-20-1-0930"],"award-info":[{"award-number":["CPMRP W81XWH-20-1-0930"]}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"crossref","award":["HT94252310330"],"award-info":[{"award-number":["HT94252310330"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"crossref","award":["PR220457P1"],"award-info":[{"award-number":["PR220457P1"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Department of Anesthesiology & Critical Care Medicine, University of New Mexico School of Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Central to the linkage of pain circuitry with the limbic system is its initial NA\u03b12-mediated antinociceptive effect in acute pain models, followed by contradictory pronociceptive activation by the locus coeruleus seen in chronic pain models. Rats with a stable, long-term (&gt;10 weeks) inflammatory compression of the trigeminal infraorbital nerve (FRICT-ION) preclinical model were given daily doxazosin, a slow-release NA\u03b11 receptor antagonist, in weeks 8\u201310. Facial hypersensitivity was reversed back to baseline in male and female rats, but anxiety was only reduced in male animals. Doxazosin-decreased astrocytic activation was indicated by a decrease in both intracranial cathepsin B imaging in vivo and GFAP immunostaining in the somatosensory cortex and hippocampus. Doxazosin reduction in NA\u03b11 receptor activation diminished glial-neuronal interactions, resulting in downstream reduction in pain-related behaviors. Other significant differences by sex included improved elevated zero maze anxiety measures only in males, and improved novel recognition scores only in females. Elevated thymus chemokine CXCL7 levels were reduced by doxazosin but only in male rats. These sexually dimorphic contradictions further complicate the understanding of the noradrenergic system\u2019s involvement in nociception. The findings indicate that by reducing NA\u03b11 receptor drive with doxazosin, the role of the locus coeruleus can be shifted back to NA\u03b12-receptor-mediated pain inhibition.<\/jats:p>","DOI":"10.3390\/ijms27052142","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:35:17Z","timestamp":1772022917000},"page":"2142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Doxazosin Alleviates Chronic Orofacial Pain"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7388-4834","authenticated-orcid":false,"given":"Karin N.","family":"Westlund","sequence":"first","affiliation":[{"name":"Research Service, New Mexico VA Health Care System, Albuquerque, NM 87108, USA"},{"name":"Department of Anesthesiology & Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-0170","authenticated-orcid":false,"given":"Bingye","family":"Xue","sequence":"additional","affiliation":[{"name":"Research Service, New Mexico VA Health Care System, Albuquerque, NM 87108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina L.","family":"McIlwrath","sequence":"additional","affiliation":[{"name":"Research Service, New Mexico VA Health Care System, Albuquerque, NM 87108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1111\/joor.13058","article-title":"Signs and symptoms, quality of life and psychosocial data in 1331 post-traumatic trigeminal neuropathy patients seen in two tertiary referral centres in two countries","volume":"47","author":"Peeters","year":"2020","journal-title":"J. Oral Rehabil."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1016\/j.mayocp.2022.01.006","article-title":"Etiologies and Utility of Diagnostic Tests in Trigeminal Neuropathy","volume":"97","author":"Ghislain","year":"2022","journal-title":"Mayo Clin. Proc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.tripleo.2004.10.014","article-title":"Neurosensory changes in the infraorbital nerve following zygomatic fractures","volume":"99","author":"Benoliel","year":"2005","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1097\/j.pain.0000000000000265","article-title":"Altered pain modulation in patients with persistent postendodontic pain","volume":"156","author":"Khan","year":"2015","journal-title":"Pain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s12663-015-0843-9","article-title":"Neuropathy of Trigeminal Nerve Branches After Oral and Maxillofacial Treatment","volume":"15","author":"Agbaje","year":"2016","journal-title":"J. Maxillofac. Oral Surg."},{"key":"ref_6","first-page":"414","article-title":"Painful Post-traumatic Trigeminal Neuropathy Occurs After Third Molar Extraction","volume":"73","author":"Busch","year":"2020","journal-title":"S. D. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1111\/jop.13078","article-title":"Molecular mechanisms of painful traumatic trigeminal neuropathy-Evidence from animal research and clinical correlates","volume":"49","author":"Korczeniewska","year":"2020","journal-title":"J. Oral Pathol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1212\/WNL.53.1.213","article-title":"Trigeminal neuropathy secondary to perineural invasion of head and neck carcinomas","volume":"53","author":"Boerman","year":"1999","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1002\/cncr.24396","article-title":"Perineural invasion in cancer: A review of the literature","volume":"115","author":"Liebig","year":"2009","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"(2020). International Classification of Orofacial Pain, 1st edition (ICOP). Cephalalgia, 40, 129\u2013221.","DOI":"10.1177\/0333102419893823"},{"key":"ref_11","unstructured":"Veerapaneni, K.D., Kapoor, N., Veerapaneni, P., Lui, F., and Nalleballe, K. (2025). Trigeminal Neuropathy. StatPearls, StatPearls Publishing."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1093\/brain\/awt211","article-title":"Shape shifting pain: Chronification of back pain shifts brain representation from nociceptive to emotional circuits","volume":"136","author":"Hashmi","year":"2013","journal-title":"Brain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.neuron.2019.03.042","article-title":"Microcircuit Mechanisms through which Mediodorsal Thalamic Input to Anterior Cingulate Cortex Exacerbates Pain-Related Aversion","volume":"102","author":"Meda","year":"2019","journal-title":"Neuron"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.neuroimage.2009.05.068","article-title":"MRI structural brain changes associated with sensory and emotional function in a rat model of long-term neuropathic pain","volume":"47","author":"Seminowicz","year":"2009","journal-title":"Neuroimage"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.neubiorev.2016.05.033","article-title":"Reward deficiency and anti-reward in pain chronification","volume":"68","author":"Borsook","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"52","DOI":"10.11607\/jop.1154","article-title":"Painful traumatic trigeminal neuropathy: An open study on the pharmacotherapeutic response to stepped treatment","volume":"28","author":"Haviv","year":"2014","journal-title":"J. Oral Facial Pain Headache"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.adaj.2015.04.001","article-title":"Prevalence of pain in the orofacial regions in patients visiting general dentists in the Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry research network","volume":"146","author":"Horst","year":"2015","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1177\/0333102417706310","article-title":"Neuropathic orofacial pain: Facts and fiction","volume":"37","author":"Benoliel","year":"2017","journal-title":"Cephalalgia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0304-3959(01)00349-9","article-title":"Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale","volume":"94","author":"Farrar","year":"2001","journal-title":"Pain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.pain.2007.08.033","article-title":"Pharmacologic management of neuropathic pain: Evidence-based recommendations","volume":"132","author":"Dworkin","year":"2007","journal-title":"Pain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/pme.12034","article-title":"Determinants of chronic pain 3 years after moderate or serious injury","volume":"14","author":"Holmes","year":"2013","journal-title":"Pain Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.jpain.2008.06.006","article-title":"Partial infraorbital nerve ligation as a model of trigeminal nerve injury in the mouse: Behavioral, neural, and glial reactions","volume":"9","author":"Xu","year":"2008","journal-title":"J. Pain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1146\/annurev.ne.14.030191.001251","article-title":"Neurotransmitters in nociceptive modulatory circuits","volume":"14","author":"Fields","year":"1991","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ejphar.2013.01.067","article-title":"The noradrenergic pain regulation system: A potential target for pain therapy","volume":"716","author":"Pertovaara","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.neuroscience.2016.05.057","article-title":"Noradrenergic Locus Coeruleus pathways in pain modulation","volume":"338","author":"Borges","year":"2016","journal-title":"Neuroscience"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/jnr.23956","article-title":"The noradrenergic locus coeruleus as a chronic pain generator","volume":"95","author":"Taylor","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0306-4522(80)90068-8","article-title":"The locus coeruleus in the rat: An immunohistochemical delineation","volume":"5","author":"Grzanna","year":"1980","journal-title":"Neuroscience"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/BF00228547","article-title":"Association of spinal lamina I projections with brainstem catecholamine neurons in the monkey","volume":"110","author":"Westlund","year":"1996","journal-title":"Exp. Brain Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"R1051","DOI":"10.1016\/j.cub.2015.09.039","article-title":"Organization of the locus coeruleus-norepinephrine system","volume":"25","author":"Schwarz","year":"2015","journal-title":"Curr. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0165-0173(80)90009-0","article-title":"Descending projections of the locus coeruleus and subcoeruleus\/medial parabrachial nuclei in monkey: Axonal transport studies and dopamine-beta-hydroxylase immunocytochemistry","volume":"2","author":"Westlund","year":"1980","journal-title":"Brain Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3109\/08990229209144768","article-title":"The origin of brainstem noradrenergic and serotonergic projections to the spinal cord dorsal horn in the rat","volume":"9","author":"Kwiat","year":"1992","journal-title":"Somatosens. Mot. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/00000542-200002000-00030","article-title":"Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 1): Effects on axon terminals of GABAergic and glycinergic neurons","volume":"92","author":"Baba","year":"2000","journal-title":"Anesthesiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.pneurobio.2006.08.001","article-title":"Noradrenergic pain modulation","volume":"80","author":"Pertovaara","year":"2006","journal-title":"Prog. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0304-3959(98)00194-8","article-title":"Differential effects of neurotoxic destruction of descending noradrenergic pathways on acute and persistent nociceptive processing","volume":"80","author":"Martin","year":"1999","journal-title":"Pain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.neuroscience.2009.02.023","article-title":"Noradrenergic neurons in the locus coeruleus contribute to neuropathic pain","volume":"160","author":"Brightwell","year":"2009","journal-title":"Neuroscience"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.neuroscience.2016.08.005","article-title":"GABA-A receptor activity in the noradrenergic locus coeruleus drives trigeminal neuropathic pain in the rat; contribution of NA\u03b11 receptors in the medial prefrontal cortex","volume":"334","author":"Kaushal","year":"2016","journal-title":"Neuroscience"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1016\/j.pain.2013.05.010","article-title":"Endogenous analgesic action of the pontospinal noradrenergic system spatially restricts and temporally delays the progression of neuropathic pain following tibial nerve injury","volume":"154","author":"Hughes","year":"2013","journal-title":"Pain"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1161\/01.RES.78.5.737","article-title":"alpha1-adrenergic receptor subtypes. Molecular structure, function, and signaling","volume":"78","author":"Graham","year":"1996","journal-title":"Circ. Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Perez, D.M. (2020). alpha(1)Adrenergic Receptors in Neurotransmission, Synaptic Plasticity, and Cognition. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.581098"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e3591","DOI":"10.21769\/BioProtoc.3591","article-title":"Minimally Invasive Oral Surgery Induction of the FRICT-ION Chronic Neuropathic Pain Model","volume":"10","author":"Montera","year":"2020","journal-title":"Bio-protocol"},{"key":"ref_41","unstructured":"Leite-Almeida, H.T.I. (2026). FRICT-ION: Simple and Reliable Trigeminal Nerve Model of Chronic Craniofacial Neuropathic Pain. Translational Research Methods for Neuropathic Pain, Springer Nature."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.biopsych.2011.07.017","article-title":"A time-dependent history of mood disorders in a murine model of neuropathic pain","volume":"70","author":"Yalcin","year":"2011","journal-title":"Biol. Psychiatry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.neubiorev.2014.08.002","article-title":"Emotional consequences of neuropathic pain: Insight from preclinical studies","volume":"47","author":"Yalcin","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_44","first-page":"333","article-title":"Profiling of patients presenting with posttraumatic neuropathy of the trigeminal nerve","volume":"25","author":"Renton","year":"2011","journal-title":"J. Orofac. Pain."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.lfs.2015.10.025","article-title":"Men and mice: Relating their ages","volume":"152","author":"Dutta","year":"2016","journal-title":"Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1176\/appi.ajp.2013.12081133","article-title":"A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan","volume":"170","author":"Raskind","year":"2013","journal-title":"Am. J. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1002\/ejp.817","article-title":"Topical prazosin attenuates sensitivity to tactile stimuli in patients with complex regional pain syndrome","volume":"20","author":"Drummond","year":"2016","journal-title":"Eur. J. Pain"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1523\/JNEUROSCI.14-05-02708.1994","article-title":"Behavioral evidence of trigeminal neuropathic pain following chronic constriction injury to the rat\u2019s infraorbital nerve","volume":"14","author":"Vos","year":"1994","journal-title":"J. Neurosci."},{"key":"ref_49","first-page":"221","article-title":"The association of chronic pain and suicide","volume":"4","author":"Fishbain","year":"1999","journal-title":"Semin. Clin. Neuropsychiatry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.bjae.2023.05.005","article-title":"Suicidality in chronic pain: Assessment and management","volume":"23","author":"Chincholkar","year":"2023","journal-title":"BJA Educ."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"100067","DOI":"10.1016\/j.ynpai.2021.100067","article-title":"Single-chain Fragment variable antibody targeting cholecystokinin-B receptor for pain reduction","volume":"10","author":"Westlund","year":"2021","journal-title":"Neurobiol. Pain"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"716","DOI":"10.2146\/ajhp070124","article-title":"Prazosin for treatment of nightmares related to posttraumatic stress disorder","volume":"65","author":"Taylor","year":"2008","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1097\/01.pra.0000364287.63210.92","article-title":"Preliminary findings concerning the use of prazosin for the treatment of posttraumatic nightmares in a refugee population","volume":"15","author":"Boynton","year":"2009","journal-title":"J. Psychiatr. Pract."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1097\/j.pain.0000000000001300","article-title":"Selective deficiencies in descending inhibitory modulation in neuropathic rats: Implications for enhancing noradrenergic tone","volume":"159","author":"Patel","year":"2018","journal-title":"Pain"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e21747","DOI":"10.1096\/fj.202100319RR","article-title":"The role of medial prefrontal cortex projections to locus ceruleus in mediating the sex differences in behavior in mice with inflammatory pain","volume":"35","author":"Cardenas","year":"2021","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0304-3959(98)00185-7","article-title":"Mechanical hyperalgesia after spinal nerve ligation in rat is not reversed by intraplantar or systemic administration of adrenergic antagonists","volume":"79","author":"Ringkamp","year":"1999","journal-title":"Pain"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.beproc.2004.03.018","article-title":"Influence of the estrous cycle on the behavior of rats in the elevated T-maze","volume":"67","author":"Gouveia","year":"2004","journal-title":"Behav. Process."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"112670","DOI":"10.1016\/j.physbeh.2019.112670","article-title":"Sex differences in anxiety-like behaviors in rats","volume":"211","author":"Scholl","year":"2019","journal-title":"Physiol. Behav."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"105733","DOI":"10.1016\/j.psyneuen.2022.105733","article-title":"Commonly-used rodent tests of anxiety-like behavior lack predictive validity for human sex differences","volume":"141","author":"Borchers","year":"2022","journal-title":"Psychoneuroendocrinology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e11892","DOI":"10.1590\/1414-431x2022e11892","article-title":"Comparison of female and male behavior in the elevated gradient of aversion","volume":"55","author":"Bonuti","year":"2022","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/0304-3940(82)90412-8","article-title":"Sex differences in alpha-adrenergic receptors in the rat brain","volume":"30","author":"Orensanz","year":"1982","journal-title":"Neurosci. Lett."},{"key":"ref_62","first-page":"PCC.11r01222","article-title":"Prazosin for the treatment of nightmares related to posttraumatic stress disorder: A review of the literature","volume":"14","author":"Hudson","year":"2012","journal-title":"Prim. Care Companion CNS Disord."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Richardson, C., Yuh, J., Su, J., and Forsberg, M. (2023). Case series: Continued remission of PTSD symptoms after discontinuation of prazosin. Front. Psychiatry, 14.","DOI":"10.3389\/fpsyt.2023.1172754"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1037\/a0016033","article-title":"Interaction of glia activation and neurotransmission in hippocampus of neuropathic rats treated with mirtazapine","volume":"17","author":"Zhu","year":"2009","journal-title":"Exp. Clin. Psychopharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Manzhulo, I., Manzhulo, O., Tyrtyshnaia, A., Ponomarenko, A., Konovalova, S., Ermolenko, E., Milkina, E., and Starinets, A. (2021). Modulation of Hippocampal Astroglial Activity by Synaptamide in Rats with Neuropathic Pain. Brain Sci., 11.","DOI":"10.3390\/brainsci11121561"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"104827","DOI":"10.1016\/j.neuint.2020.104827","article-title":"Melatonin reduces neuropathic pain behavior and glial activation through MT2 melatonin receptor modulation in a rat model of lysophosphatidylcholine-induced demyelination neuropathy","volume":"140","author":"Huang","year":"2020","journal-title":"Neurochem. Int."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"46504","DOI":"10.1074\/jbc.M103849200","article-title":"Alpha 1-adrenergic modulation of metabotropic glutamate receptor-induced calcium oscillations and glutamate release in astrocytes","volume":"276","author":"Muyderman","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1002\/glia.24591","article-title":"The astrocyte \u03b11A-adrenoreceptor is a key component of the neuromodulatory system in mouse visual cortex","volume":"72","author":"Wahis","year":"2024","journal-title":"Glia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"104942","DOI":"10.1016\/j.neuint.2020.104942","article-title":"Astroglial adrenoreceptors modulate synaptic transmission and contextual fear memory formation in dentate gyrus","volume":"143","author":"Shen","year":"2021","journal-title":"Neurochem. Int."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/35094583","article-title":"Cytokines and acute neurodegeneration","volume":"2","author":"Allan","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/00000542-200401000-00024","article-title":"Mobilization of opioid-containing polymorphonuclear cells by hematopoietic growth factors and influence on inflammatory pain","volume":"100","author":"Brack","year":"2004","journal-title":"Anesthesiology"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Marciano, C.L., Hiland, T.A., Jackson, K.L., Street, S., Maris, C., Ehrsam, A., Hum, J.M., Loghmani, M.T., Chu, T.M.G., and Kang, K.S. (2023). Soft Tissue Manipulation Alters RANTES\/CCL5 and IL-4 Cytokine Levels in a Rat Model of Chronic Low Back Pain. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202307.1560.v1"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e2501229122","DOI":"10.1073\/pnas.2501229122","article-title":"A prolactin-targeting antibody to prevent stress-induced peripheral nociceptor sensitization and female postoperative pain","volume":"122","author":"Stratton","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cca.2007.01.026","article-title":"Adiponectin as an anti-inflammatory factor","volume":"380","author":"Ouchi","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.3899\/jrheum.090113","article-title":"Perturbed insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 are not associated with chronic widespread pain in men: Results from the European Male Ageing Study","volume":"36","author":"McBeth","year":"2009","journal-title":"J. Rheumatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4675","DOI":"10.1074\/jbc.M207006200","article-title":"Chemokine-cytokine cross-talk. The ELR+ CXC chemokine LIX (CXCL5) amplifies a proinflammatory cytokine response via a phosphatidylinositol 3-kinase-NF-kappa B pathway","volume":"278","author":"Chandrasekar","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.2522\/ptj.20130597","article-title":"Chronic stress, cortisol dysfunction, and pain: A psychoneuroendocrine rationale for stress management in pain rehabilitation","volume":"94","author":"Hannibal","year":"2014","journal-title":"Phys. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1080\/15287397809529700","article-title":"Concentrations of circulating steroids in normal prepubertal and adult male and female humans, chimpanzees, rhesus monkeys, rats, mice, and hamsters: A literature survey","volume":"4","author":"Overpeck","year":"1978","journal-title":"J. Toxicol. Environ. Health"},{"key":"ref_79","first-page":"293","article-title":"Effects of antihypertensive therapy on blood pressure and renal function in rats with hypertension due to chronic blockade of nitric oxide synthesis","volume":"3","author":"Erley","year":"1995","journal-title":"Exp. Nephrol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"117343","DOI":"10.1016\/j.neuroimage.2020.117343","article-title":"Manganese-enhanced MRI reveals changes within brain anxiety and aversion circuitry in rats with chronic neuropathic pain- and anxiety-like behaviors","volume":"223","author":"McIlwrath","year":"2020","journal-title":"Neuroimage"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1756-6606-5-44","article-title":"Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC) of the infraorbital nerve","volume":"5","author":"Ma","year":"2012","journal-title":"Mol. Brain"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0165-0270(94)90144-9","article-title":"Quantitative assessment of tactile allodynia in the rat paw","volume":"53","author":"Chaplan","year":"1994","journal-title":"J. Neurosci. Methods"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/1744-8069-10-66","article-title":"Cannabinoid receptor 2 agonist attenuates pain related behavior in rats with chronic alcohol\/high fat diet induced pancreatitis","volume":"10","author":"Zhang","year":"2014","journal-title":"Mol. Pain"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/BF02244871","article-title":"Behavioural and pharmacological characterisation of the elevated \u201czero-maze\u201d as an animal model of anxiety","volume":"116","author":"Shepherd","year":"1994","journal-title":"Psychopharmacology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0166-4328(88)90157-X","article-title":"A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data","volume":"31","author":"Ennaceur","year":"1988","journal-title":"Behav. Brain Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1750-1326-9-30","article-title":"Neuroinflammation and neurologic deficits in diabetes linked to brain accumulation of amylin","volume":"9","author":"Srodulski","year":"2014","journal-title":"Mol. Neurodegener."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4517","DOI":"10.1038\/s41598-024-52854-2","article-title":"In vivo imaging of cathepsin B in activated glia in the brain after orofacial formalin test","volume":"14","author":"McIlwrath","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s12264-018-0223-9","article-title":"Rat Cerebrospinal Fluid Treatment Method through Cisterna Cerebellomedullaris Injection","volume":"34","author":"Pereira","year":"2018","journal-title":"Neurosci. Bull."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"104906","DOI":"10.1016\/j.psyneuen.2020.104906","article-title":"Restraint stress affects circulating NUCB2\/nesfatin-1 and phoenixin levels in male rats","volume":"122","author":"Schalla","year":"2020","journal-title":"Psychoneuroendocrinology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2142\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:24:44Z","timestamp":1772169884000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":90,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27052142"],"URL":"https:\/\/doi.org\/10.3390\/ijms27052142","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]}}}