{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T21:01:07Z","timestamp":1784667667309,"version":"3.55.0"},"reference-count":105,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,9]],"date-time":"2023-04-09T00:00:00Z","timestamp":1680998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Pain is the most common symptom that dentists are confronted with, whether acute (pulpitis, acute periodontitis, post-surgery, etc.) or chronic diseases, such as periodontitis, muscle pain, temporomandibular joint (TMJ) disorders, burning mouth syndrome (BMS), oral lichen planus (OLP) and others. The success of therapy depends on the reduction in and management of pain through specific drugs, hence the need to analyze new pain medications with specific activity, which are suitable for long-term use, with a low risk of side effects and interactions with other drugs, and capable of leading to a reduction in orofacial pain. Palmitoylethanolamide (PEA) is a bioactive lipid mediator, which is synthesized in all tissues of the body as a protective pro-homeostatic response to tissue damage and has aroused considerable interest in the dental field due to its anti-inflammatory, analgesic, antimicrobial, antipyretic, antiepileptic, immunomodulatory and neuroprotective activities. It has been observed that PEA could play a role in the management of the pain of orofacial origin, including BMS, OLP, periodontal disease, tongue a la carte and temporomandibular disorders (TMDs), as well as in the treatment of postoperative pain. However, actual clinical data on the use of PEA in the clinical management of patients with orofacial pain are still lacking. Therefore, the main objective of the present study is to provide an overview of orofacial pain in its many manifestations and an updated analysis of the molecular pain-relieving and anti-inflammatory properties of PEA to understand its beneficial effects in the management of patients with orofacial pain, both neuropathic and nociceptive in nature. The aim is also to direct research toward the testing and use of other natural agents that have already been shown to have anti-inflammatory, antioxidant and pain-relieving actions and could offer important support in the treatment of orofacial pain.<\/jats:p>","DOI":"10.3390\/pharmaceutics15041193","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:15:57Z","timestamp":1681096557000},"page":"1193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Orofacial Pain Management: An Overview of the Potential Benefits of Palmitoylethanolamide and Other Natural Agents"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1020-4341","authenticated-orcid":false,"given":"Simona","family":"Santonocito","sequence":"first","affiliation":[{"name":"Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2978-5772","authenticated-orcid":false,"given":"Martina","family":"Donzella","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9849-8342","authenticated-orcid":false,"given":"Pietro","family":"Venezia","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Nicolosi","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4008-6502","authenticated-orcid":false,"given":"Rodolfo","family":"Mauceri","sequence":"additional","affiliation":[{"name":"Department of Surgical, Oncological, and Oral Sciences, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4267-6992","authenticated-orcid":false,"given":"Gaetano","family":"Isola","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1097\/j.pain.0000000000001939","article-title":"The revised IASP definition of pain: Concepts, challenges, and compromises","volume":"161","author":"Raja","year":"2020","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1001\/jama.280.21.1863","article-title":"Symptomatic treatment of painful neuropathy","volume":"280","author":"Low","year":"1998","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/head.13689","article-title":"Tooth-Related Pain or Not?","volume":"60","author":"Renton","year":"2020","journal-title":"Headache"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1159\/000505727","article-title":"Facial Pain: A Comprehensive Review and Proposal for a Pragmatic Diagnostic Approach","volume":"83","author":"Goessens","year":"2020","journal-title":"Eur. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.oooo.2021.07.021","article-title":"Neuropathic orofacial pain: Characterization of different patient groups using the ICOP first edition, in a tertiary level Orofacial Pain Clinic","volume":"132","author":"Handa","year":"2021","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.pain.2010.09.030","article-title":"Central sensitization: Implications for the diagnosis and treatment of pain","volume":"152","author":"Woolf","year":"2011","journal-title":"Pain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1177\/10454411990100010101","article-title":"Dental injury models: Experimental tools for understanding neuroinflammatory interactions and polymodal nociceptor functions","volume":"10","author":"Byers","year":"1999","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/scd.12323","article-title":"Applications of sensory and physiological measurement in oral-facial dental pain","volume":"38","author":"Dabiri","year":"2018","journal-title":"Spec. Care Dent."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1177\/002203458506400412","article-title":"The role of local factors in dentin and pulp in intradental pain mechanisms","volume":"64","author":"Olgart","year":"1985","journal-title":"J. Dent. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2334\/josnusd.49.89","article-title":"Oral lichen planus and lichenoid reactions: Etiopathogenesis, diagnosis, management and malignant transformation","volume":"49","author":"Ismail","year":"2007","journal-title":"J. Oral Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1177\/197140090001300316","article-title":"Patologia dell\u2019articolazione temporo-mandibolare","volume":"13","author":"Michelozzi","year":"2000","journal-title":"Riv. Neuroradiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1016\/S0140-6736(99)01307-0","article-title":"Neuropathic pain: Aetiology, symptoms, mechanisms, and management","volume":"353","author":"Woolf","year":"1999","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1196\/annals.1366.016","article-title":"Therapeutic management of chronic neuropathic pain: An examination of pharmacologic treatment","volume":"1088","author":"Vadalouca","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s00702-005-0300-x","article-title":"Evidence-based pharmacological treatment of neuropathic pain syndromes","volume":"112","author":"Beniczky","year":"2005","journal-title":"J. Neural Transm."},{"key":"ref_15","first-page":"117","article-title":"Pain and pain behavior in burning mouth syndrome: A pain diary study","volume":"26","author":"Forssell","year":"2012","journal-title":"J. Orofac. Pain"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1477-7525-9-57","article-title":"The impact of burning mouth syndrome on health-related quality of life","volume":"9","author":"Souza","year":"2011","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0304-3959(02)00052-0","article-title":"Sensory dysfunction in burning mouth syndrome","volume":"99","author":"Forssell","year":"2002","journal-title":"Pain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S0304-3959(97)00140-1","article-title":"Abnormalities of the blink reflex in burning mouth syndrome","volume":"73","author":"Forssell","year":"1997","journal-title":"Pain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1111\/joor.13250","article-title":"A conceptual model of oro-facial health with an emphasis on function","volume":"48","author":"Schimmel","year":"2021","journal-title":"J. Oral Rehabil."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"(2020). International Classification of Orofacial Pain, 1st edition (ICOP). Cephalalgia, 40, 129\u2013221.","DOI":"10.1177\/0333102419893823"},{"key":"ref_21","first-page":"ix","article-title":"Orofacial Pain: Where We Are and Where We Are Going","volume":"62","author":"Bender","year":"2018","journal-title":"Dent. Clin."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Clayton, P., Hill, M., Bogoda, N., Subah, S., and Venkatesh, R. (2021). Palmitoylethanolamide: A Natural Compound for Health Management. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105305"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3389\/fncel.2014.00138","article-title":"Strategies to increase the activity of microglia as efficient protectors of the brain against infections","volume":"8","author":"Nau","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2174\/1871527311312010010","article-title":"Palmitoylethanolamide in homeostatic and traumatic central nervous system injuries","volume":"12","author":"Esposito","year":"2013","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.neuropharm.2012.11.017","article-title":"Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-\u03b1 receptor activation in a genetic model of absence epilepsy","volume":"69","author":"Citraro","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/bph.12907","article-title":"Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent","volume":"172","author":"Borrelli","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1111\/bph.13580","article-title":"The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations","volume":"174","author":"Petrosino","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rankin, L., and Fowler, C.J. (2020). The Basal Pharmacology of Palmitoylethanolamide. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217942"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Gugliandolo, E., Peritore, A.F., Piras, C., Cuzzocrea, S., and Crupi, R. (2020). Palmitoylethanolamide and related aliamides: Prohomeostatic lipid compounds for animal health and wellbeing. Vet. Sci., 7.","DOI":"10.3390\/vetsci7020078"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1111\/bcp.13020","article-title":"Palmitoylethanolamide for the treatment of pain: Pharmacokinetics, safety and efficacy","volume":"82","author":"Gabrielsson","year":"2016","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13005-020-00244-0","article-title":"Analogous modulation of inflammatory responses by the endocannabinoid system in periodontal ligament cells and microglia","volume":"16","author":"Setiawan","year":"2020","journal-title":"Head Face Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s00784-020-03397-z","article-title":"Effectiveness of a nutraceutical agent in the non-surgical periodontal therapy: A randomized, controlled clinical trial","volume":"25","author":"Isola","year":"2021","journal-title":"Clin. Oral Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1515\/jcim-2021-0434","article-title":"Burning mouth syndrome: A review of therapeutic approach","volume":"19","author":"Nosratzehi","year":"2021","journal-title":"J. Complement. Integr. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Siracusa, R., Fusco, R., Cordaro, M., Peritore, A.F., D\u2019Amico, R., Gugliandolo, E., Crupi, R., Genovese, T., Evangelista, M., and Di Paola, R. (2020). The Protective Effects of Pre- and Post-Administration of Micronized Palmitoylethanolamide Formulation on Postoperative Pain in Rats. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207700"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rankin, L., Gouveia-Figueira, S., Danielsson, K.P., and Fowler, C.J. (2020). Relative Deficiency of Anti-Inflammatory N-Acylethanolamines Compared to Prostaglandins in Oral Lichen Planus. Biomedicines, 8.","DOI":"10.3390\/biomedicines8110481"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1007\/s00784-018-2720-7","article-title":"Efficacy of ultramicronized palmitoylethanolamide in burning mouth syndrome-affected patients: A preliminary randomized double-blind controlled trial","volume":"23","author":"Ottaviani","year":"2019","journal-title":"Clin. Oral Investig."},{"key":"ref_37","first-page":"99","article-title":"Palmitoylethanolamide versus a nonsteroidal anti-inflammatory drug in the treatment of temporomandibular joint inflammatory pain","volume":"26","author":"Marini","year":"2012","journal-title":"J. Orofac. Pain"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"961","DOI":"10.14219\/jada.archive.1979.0421","article-title":"Recognition and treatment of patients with chronic orofacial pain","volume":"99","author":"Donaldson","year":"1979","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_39","first-page":"209","article-title":"Neuropathic orofacial pain: Proposed mechanisms, diagnosis, and treatment considerations","volume":"51","author":"Spencer","year":"2007","journal-title":"Dent. Clin."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.jpain.2009.06.012","article-title":"Central sensitization: A generator of pain hypersensitivity by central neural plasticity","volume":"10","author":"Latremoliere","year":"2009","journal-title":"J. Pain"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2344\/0003-3006-57.2.67","article-title":"Pain management: Part 1: Managing acute and postoperative dental pain","volume":"57","author":"Becker","year":"2010","journal-title":"Anesth. Prog."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1111\/j.1834-7819.2007.tb00525.x","article-title":"An overview of the dental pulp: Its functions and responses to injury","volume":"52","author":"Yu","year":"2007","journal-title":"Aust. Dent. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1177\/204946371100500102","article-title":"Dental (odontogenic) pain","volume":"5","author":"Renton","year":"2011","journal-title":"Rev. Pain"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1177\/0022034516657070","article-title":"Pain Mechanisms and Centralized Pain in Temporomandibular Disorders","volume":"95","author":"Harper","year":"2016","journal-title":"J. Dent. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.coms.2007.12.001","article-title":"Neuropathic orofacial pain","volume":"20","author":"Benoliel","year":"2008","journal-title":"Oral Maxillofac. Surg. Clin. N. Am."},{"key":"ref_46","unstructured":"Mongini, F. (1998). Le Cefalee e il Dolore Facciale, UTET."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1056\/NEJMra1914484","article-title":"Trigeminal Neuralgia","volume":"383","author":"Cruccu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2174\/1570159X17666191010094350","article-title":"Trigeminal Neuralgia: Basic and Clinical Aspects","volume":"18","author":"Araya","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"36042","DOI":"10.52965\/001c.36042","article-title":"Glossopharyngeal Neuralgia: Epidemiology, Risk factors, Pathophysiology, Differential diagnosis, and Treatment Options","volume":"10","author":"Han","year":"2022","journal-title":"Health Psychol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1001\/archneur.1981.00510040027002","article-title":"Glossopharyngeal (vagoglossopharyngeal) neuralgia: A study of 217 cases","volume":"38","author":"Rushton","year":"1981","journal-title":"Arch. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Giovannini, S., Coraci, D., Brau, F., Galluzzo, V., Loreti, C., Caliandro, P., Padua, L., Maccauro, G., Biscotti, L., and Bernabei, R. (2021). Neuropathic Pain in the Elderly. Diagnostics, 11.","DOI":"10.3390\/diagnostics11040613"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s00776-012-0209-9","article-title":"Neural mechanisms underlying deafferentation pain: A hypothesis from a neuroimaging perspective","volume":"17","author":"Hanakawa","year":"2012","journal-title":"J. Orthop. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1177\/204946371100500404","article-title":"Persistent dento-alveolar pain disorder (PDAP): Working towards a better understanding","volume":"5","author":"Nixdorf","year":"2011","journal-title":"Rev. Pain"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13030-017-0106-8","article-title":"Clinical features of atypical odontalgia; three cases and literature reviews","volume":"11","author":"Takenoshita","year":"2017","journal-title":"Biopsychosoc. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1177\/154411130301400405","article-title":"Update on burning mouth syndrome: Overview and patient management","volume":"14","author":"Scala","year":"2003","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.clinph.2011.07.054","article-title":"Pathophysiology of primary burning mouth syndrome","volume":"123","year":"2012","journal-title":"Clin. Neurophysiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1111\/j.1365-2842.1995.tb00237.x","article-title":"General health factors and denture function in patients with burning mouth syndrome and matched control subjects","volume":"22","author":"Svensson","year":"1995","journal-title":"J. Oral Rehabil."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1002\/ejp.1382","article-title":"Neurophysiology and genetics of burning mouth syndrome","volume":"23","author":"Kolkka","year":"2019","journal-title":"Eur. J. Pain"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1046\/j.1440-1819.2002.00950.x","article-title":"Pain threshold and pain recovery after experimental stimulation in patients with burning mouth syndrome","volume":"56","author":"Ito","year":"2002","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.jocn.2006.09.002","article-title":"Burning mouth syndrome as a trigeminal small fibre neuropathy: Increased heat and capsaicin receptor TRPV1 in nerve fibres correlates with pain score","volume":"14","author":"Yilmaz","year":"2007","journal-title":"J. Clin. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/odi.12454","article-title":"Peripheral nervous system involvement in primary burning mouth syndrome\u2014Results of a pilot study","volume":"22","author":"Puhakka","year":"2016","journal-title":"Oral Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0304-3959(02)00323-8","article-title":"Striatal dopamine D1 and D2 receptors in burning mouth syndrome","volume":"101","author":"Hagelberg","year":"2003","journal-title":"Pain"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ejphar.2018.07.038","article-title":"Dopaminergic and serotonergic mechanisms in the modulation of pain: In vivo studies in human brain","volume":"834","author":"Martikainen","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1111\/j.1529-8019.2008.00228.x","article-title":"Contribution of neuroinflammation in burning mouth syndrome: Indications from benzodiazepine use","volume":"21","author":"Guarneri","year":"2008","journal-title":"Dermatol. Ther."},{"key":"ref_65","first-page":"e144","article-title":"Etiology of burning mouth syndrome: A review and update","volume":"16","year":"2011","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/0030-4220(89)90269-7","article-title":"Oral discomfort at menopause","volume":"67","author":"Wardrop","year":"1989","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0003-9969(95)00085-2","article-title":"Effect of hormone replacement therapy on salivary flow rate, buffer effect and pH on perimenopausal and postmenopausal women","volume":"41","author":"Laine","year":"1996","journal-title":"Arch. Oral Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/odi.12660","article-title":"Burning mouth syndrome: A systematic review of treatments","volume":"24","author":"Liu","year":"2018","journal-title":"Oral Dis."},{"key":"ref_69","first-page":"1","article-title":"Elettromiografia dei muscoli masticatori non \u00e8 utile in ambito medico legale","volume":"6","author":"Manfredini","year":"2008","journal-title":"Tagete-Arch. Leg. Med. Dent."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1097\/SPC.0000000000000445","article-title":"Myofascial pain syndrome and trigger points: Evaluation and treatment in patients with musculoskeletal pain","volume":"13","author":"Barbero","year":"2019","journal-title":"Curr. Opin. Support Palliat. Care"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"821","DOI":"10.3389\/fphar.2019.00821","article-title":"Palmitoylethanolamide (PEA) as a potential therapeutic agent in Alzheimer\u2019s disease","volume":"10","author":"Beggiato","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1038\/npp.2012.25","article-title":"Palmitoylethanolamide protects against the amyloid-\u03b225-35-induced learning and memory impairment in mice, an experimental model of Alzheimer disease","volume":"37","author":"Russo","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1210\/er.2018-00064","article-title":"Molecular actions of PPAR \u03b1 in lipid metabolism and inflammation","volume":"39","author":"Bougarne","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1007\/s11064-020-02993-5","article-title":"The novel role of PPAR alpha in the brain: Promising target in therapy of Alzheimer\u2019s disease and other neurodegenerative disorders","volume":"45","author":"Strosznajder","year":"2020","journal-title":"Neurochem. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/sj.bjp.0706348","article-title":"Inhibitors of fatty acid amide hydrolase reduce carrageenan-induced hind paw inflammation in pentobarbital-treated mice: Comparison with indomethacin and possible involvement of cannabinoid receptors","volume":"146","author":"Holt","year":"2005","journal-title":"Br. J. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1016\/j.pain.2012.04.020","article-title":"An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee","volume":"153","author":"Huggins","year":"2012","journal-title":"Pain"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s00011-019-01273-5","article-title":"The effect of palmitic acid on inflammatory response in macrophages: An overview of molecular mechanisms","volume":"68","author":"Korbecki","year":"2019","journal-title":"Inflamm. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1002\/mnfr.201400314","article-title":"Fatty acid chain length and saturation influences PPAR\u03b1 transcriptional activation and repression in HepG2 cells","volume":"58","author":"Popeijus","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e00300","DOI":"10.1002\/prp2.300","article-title":"The anti-inflammatory compound palmitoylethanolamide inhibits prostaglandin and hydroxyeicosatetraenoic acid production by a macrophage cell line","volume":"5","author":"Gabrielsson","year":"2017","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"C145","DOI":"10.1007\/BF01972748","article-title":"A proposed autacoid mechanism controlling mastocyte behaviour","volume":"39","author":"Aloe","year":"1993","journal-title":"Agents Actions"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Hesselink, J.K., de Boer, T., and Witkamp, R.F. (2013). Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, GIHI Chemicals.","DOI":"10.1155\/2013\/151028"},{"key":"ref_82","first-page":"21","article-title":"Anticoagulant therapy in patients undergoing dental interventions: A critical review of the literature and current perspectives","volume":"64","author":"Isola","year":"2015","journal-title":"Minerva Stomatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/imm.12170","article-title":"Mast cells, glia and neuroinflammation: Partners in crime?","volume":"141","author":"Skaper","year":"2014","journal-title":"Immunology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1111\/febs.12152","article-title":"Metabolism of endocannabinoids and related N-acylethanolamines: Canonical and alternative pathways","volume":"280","author":"Ueda","year":"2013","journal-title":"FEBS J."},{"key":"ref_85","first-page":"523","article-title":"Epithelial expression of vanilloid and cannabinoid receptors: A potential role in burning mouth syndrome pathogenesis","volume":"29","author":"Borsani","year":"2014","journal-title":"Histol. Histopathol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/jop.12692","article-title":"Plasma N-acylethanolamine and endocannabinoid levels in burning mouth syndrome: Potential role in disease pathogenesis","volume":"47","author":"Barry","year":"2018","journal-title":"J. Oral Pathol. Med."},{"key":"ref_87","first-page":"1274","article-title":"Enzymological studies on the biosynthesis of N-acylethanolamines","volume":"1801","author":"Ueda","year":"2010","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Biol. Lipids"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.pain.2008.06.003","article-title":"The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: Involvement of CB1, TRPV1 and PPAR\u03b3 receptors and neurotrophic factors","volume":"139","author":"Costa","year":"2008","journal-title":"Pain"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"34","DOI":"10.2174\/1871527311312010008","article-title":"Non-neuronal cell modulation relieves neuropathic pain: Efficacy of the endogenous lipid palmitoylethanolamide","volume":"12","author":"Bettoni","year":"2013","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Ardizzone, A., Fusco, R., Casili, G., Lanza, M., Impellizzeri, D., Esposito, E., and Cuzzocrea, S. (2021). Effect of Ultra-Micronized-Palmitoylethanolamide and Acetyl-l-Carnitine on Experimental Model of Inflammatory Pain. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041967"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ejphar.2016.03.033","article-title":"A new co-micronized composite containing palmitoylethanolamide and polydatin shows superior oral efficacy compared to their association in a rat paw model of carrageenan-induced inflammation","volume":"782","author":"Esposito","year":"2016","journal-title":"Eur. J. Pharm."},{"key":"ref_92","first-page":"46","article-title":"Ethnopharmacology, phytochemistry and biological activities of the African species of the genus Ficus","volume":"6","author":"Olaoluwa","year":"2022","journal-title":"Trends Phytochem. Res."},{"key":"ref_93","first-page":"110","article-title":"Phytochemistry, traditional uses, and pharmacology of the genus Ekebergia (Meliaceae): A review","volume":"5","author":"Dzouemo","year":"2021","journal-title":"Trends Phytochem. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.2174\/1385272823666191007161550","article-title":"Ethnobotany and phytochemistry of the genus Eremostachys Bunge","volume":"23","author":"Mohammadhosseini","year":"2019","journal-title":"Curr. Org. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1080\/15569543.2019.1691013","article-title":"The genus Perovskia Kar.: Ethnobotany, chemotaxonomy and phytochemistry: A review","volume":"40","author":"Mohammadhosseini","year":"2021","journal-title":"Toxin Rev."},{"key":"ref_96","first-page":"31","article-title":"Phytochemical, ethanomedicinal and pharmacological applications of escin from Aesculus hippocastanum L. towards future medicine","volume":"10","author":"Idris","year":"2020","journal-title":"J. Basic Clin. Physiol. Pharm."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.2174\/0929867327666200713184138","article-title":"Recent Research on Flavonoids and their Biomedical Applications","volume":"28","author":"Wen","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"478","DOI":"10.3389\/fnins.2020.00478","article-title":"Exploring the Promise of Flavonoids to Combat Neuropathic Pain: From Molecular Mechanisms to Therapeutic Implications","volume":"14","author":"Uddin","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.2174\/1389557519666190617150051","article-title":"The Roles of Flavonols\/Flavonoids in Neurodegeneration and Neuroinflammation","volume":"20","author":"Calis","year":"2020","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.2147\/DDDT.S207720","article-title":"Escin: A review of its anti-edematous, anti-inflammatory, and venotonic properties","volume":"13","author":"Gallelli","year":"2019","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"245","DOI":"10.4142\/jvs.2017.18.2.245","article-title":"Efficacy of horse chestnut leaf extract ALH-L1005 as a matrix metalloproteinase inhibitor in ligature-induced periodontitis in canine model","volume":"18","author":"Kim","year":"2017","journal-title":"J. Vet Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1111\/jphp.13129","article-title":"Scutellaria baicalensis Georgi. (Lamiaceae): A review of its traditional uses, botany, phytochemistry, pharmacology and toxicology","volume":"71","author":"Zhao","year":"2019","journal-title":"J. Pharm. Pharm."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"110917","DOI":"10.1016\/j.biopha.2020.110917","article-title":"The main bioactive compounds of Scutellaria baicalensis Georgi. for alleviation of inflammatory cytokines: A comprehensive review","volume":"133","author":"Liao","year":"2021","journal-title":"Biomed. Pharm."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ejmech.2017.03.004","article-title":"Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders","volume":"131","author":"Dinda","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.brainresbull.2020.08.016","article-title":"Anti-inflammatory and immunomodulatory effects of baicalin in cerebrovascular and neurological disorders","volume":"164","author":"Li","year":"2020","journal-title":"Brain Res. Bull."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/4\/1193\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:12:40Z","timestamp":1760123560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/4\/1193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,9]]},"references-count":105,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["pharmaceutics15041193"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15041193","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,9]]}}}