{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:08:55Z","timestamp":1787162935144,"version":"build-2736575974"},"reference-count":103,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Refractory neuropathic pain of the head and neck remains a major clinical challenge, particularly when mediated through the cervicotrigeminal complex (CTC), a unique anatomical hub integrating trigeminal and upper cervical nociceptive inputs. This narrative review synthesizes neuroanatomical, pathophysiological, and clinical evidence to provide a unifying framework for diagnosis and management. A structured search of PubMed, Scopus, and Web of Science identified English-language clinical and mechanistic studies addressing CTC-mediated pain, with case reports excluded unless mechanistically informative. We propose multidimensional refractoriness criteria that integrate pharmacological non-response, failed interventional strategies, and objective functional impairment. Current treatments span pharmacotherapy, peripheral interventions (nerve blocks, radiofrequency ablation), and neuromodulation at multiple network levels (occipital nerve stimulation, spinal cord stimulation, motor cortex stimulation, deep brain stimulation). Non-invasive approaches such as rTMS, tDCS, and vagus nerve stimulation are emerging but remain investigational. Advances in imaging and neurophysiological biomarkers now permit greater precision in detecting CTC dysfunction and tailoring therapy. By combining anatomical precision, mechanistic insight, and multidisciplinary strategies, this review proposes a clinically actionable definition of refractoriness and supports a stepwise, mechanism-based approach to therapy. CTC emerges as a targetable hub for diagnostic and therapeutic strategies in refractory head and neck pain.<\/jats:p>","DOI":"10.3390\/life15091457","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T13:03:02Z","timestamp":1758114182000},"page":"1457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Refractory Neuropathic Pain in the Head and Neck: Neuroanatomical and Clinical Significance of the Cervicotrigeminal Complex"],"prefix":"10.3390","volume":"15","author":[{"given":"Marina","family":"Ragu\u017e","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Dubrava University Hospital, 10000 Zagreb, Croatia"},{"name":"School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4173-1278","authenticated-orcid":false,"given":"Marko","family":"Tarle","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery, Dubrava University Hospital, 10000 Zagreb, Croatia"},{"name":"School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7058-4123","authenticated-orcid":false,"given":"Koraljka","family":"Hat","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery, Dubrava University Hospital, 10000 Zagreb, Croatia"},{"name":"School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Salari\u0107","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery, Dubrava University Hospital, 10000 Zagreb, Croatia"},{"name":"School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petar","family":"Mar\u010dinkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Dubrava University Hospital, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Bi\u010dani\u0107","sequence":"additional","affiliation":[{"name":"School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Lazi\u0107 Mosler","sequence":"additional","affiliation":[{"name":"School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9138-2037","authenticated-orcid":false,"given":"Ivica","family":"Luk\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery, Dubrava University Hospital, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonko","family":"Marinovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Dubrava University Hospital, 10000 Zagreb, Croatia"},{"name":"Medicine of Sports and Exercise Chair, Faculty of Kinesiology, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darko","family":"Chudy","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Dubrava University Hospital, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"ref_1","unstructured":"IASP (2025, August 30). IASP Terminology: Neuropathic Pain Definition. International Association for the Study of Pain. Available online: https:\/\/www.iasp-pain.org\/resources\/terminology\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/j.pain.0000000000001384","article-title":"Chronic pain as a symptom or a disease: The IASP Classification of Chronic Pain for the ICD-11","volume":"160","author":"Treede","year":"2019","journal-title":"Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1001\/archneur.60.11.1524","article-title":"Advances in neuropathic pain: Diagnosis, mechanisms, and treatment recommendations","volume":"60","author":"Dworkin","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/j.pain.2011.06.017","article-title":"A new definition of neuropathic pain","volume":"152","author":"Jensen","year":"2011","journal-title":"Pain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(14)70251-0","article-title":"Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis","volume":"14","author":"Finnerup","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.pain.2007.08.013","article-title":"Prevalence of chronic pain with neuropathic characteristics in the general population","volume":"136","author":"Bouhassira","year":"2008","journal-title":"Pain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.pain.2013.11.013","article-title":"Neuropathic pain in the general population: A systematic review of epidemiological studies","volume":"155","author":"Austin","year":"2014","journal-title":"Pain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17002","DOI":"10.1038\/nrdp.2017.2","article-title":"Neuropathic pain","volume":"3","author":"Colloca","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s11916-012-0256-0","article-title":"Epidemiology of neuropathic pain and its impact on quality of life","volume":"16","author":"Smith","year":"2012","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.jpain.2005.11.008","article-title":"The epidemiology of chronic pain of predominantly neuropathic origin: Results from a general population survey","volume":"7","author":"Torrance","year":"2006","journal-title":"J. Pain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.anorl.2024.09.008","article-title":"Trigeminal cervical complex: A neural network affecting the head and neck","volume":"142","author":"Hosri","year":"2025","journal-title":"Eur. Ann. Otorhinolaryngol. Head Neck Dis."},{"key":"ref_12","first-page":"67","article-title":"The anatomical basis for cervicogenic headache","volume":"15","author":"Bogduk","year":"1992","journal-title":"J. Manip. Physiol. Ther."},{"key":"ref_13","unstructured":"Merskey, H., and Bogduk, N. (1994). Classification of Chronic Pain, IASP Press. [2nd ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s11916-003-0037-x","article-title":"Convergence of cervical and trigeminal sensory afferents","volume":"7","author":"Piovesan","year":"2003","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_15","first-page":"21","article-title":"Utjecaj manualne terapije vratne kraljeznice na tipicnu trigeminalnu neuralgiju: Prikaz bolesnice [Influence of manual therapy of cervical spine on typical trigeminal neuralgia: A case report]","volume":"132","year":"2010","journal-title":"Lijec Vjesn."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s11916-003-0036-y","article-title":"The trigeminocervical complex and migraine: Current concepts and synthesis","volume":"7","author":"Bartsch","year":"2003","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S1474-4422(09)70209-1","article-title":"Cervicogenic headache: An assessment of the evidence on clinical diagnosis, invasive tests, and treatment","volume":"8","author":"Bogduk","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_18","first-page":"164","article-title":"Migraine and the trigeminocervical complex","volume":"9","author":"Bartsch","year":"2005","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0304-3959(86)90213-7","article-title":"Convergence of cutaneous, tooth pulp, visceral, neck and muscle afferents onto nociceptive and non-nociceptive neurones in trigeminal subnucleus caudalis (medullary dorsal horn) and its implications for referred pain","volume":"27","author":"Sessle","year":"1986","journal-title":"Pain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1152\/physrev.00034.2015","article-title":"Pathophysiology of Migraine: A Disorder of Sensory Processing","volume":"97","author":"Goadsby","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Headache Classification Committee of the International Headache Society (IHS) (2018). The International Classification of Headache Disorders, 3rd edition (ICHD-3). Cephalalgia, 38, 1\u2013211.","DOI":"10.1177\/0333102417738202"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1055\/s-0042-1758043","article-title":"Recent Advances and Updates in Trigeminal Autonomic Cephalalgias","volume":"42","author":"Wei","year":"2022","journal-title":"Semin. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/ene.13950","article-title":"European Academy of Neurology guideline on trigeminal neuralgia","volume":"26","author":"Bendtsen","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1129-2377-15-47","article-title":"Refractory chronic migraine: A consensus statement on clinical definition from the European Headache Federation","volume":"15","author":"Martelletti","year":"2014","journal-title":"J. Headache Pain."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1016\/S0140-6736(20)32342-4","article-title":"Migraine: Integrated approaches to clinical management and emerging treatments","volume":"397","author":"Ashina","year":"2021","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1177\/0333102417694884","article-title":"Altered brainstem anatomy in migraine","volume":"38","author":"Marciszewski","year":"2017","journal-title":"Cephalalgia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1097\/j.pain.0000000000002417","article-title":"Experimental evidence of a functional relationship within the brainstem trigeminocervical complex in humans","volume":"163","author":"Basedau","year":"2022","journal-title":"Pain"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/0014-4886(61)90036-X","article-title":"Structural relation of the spinal trigeminal nucleus to the upper cervical roots and the subnucleus caudalis of the nucleus of the tractus solitarius in the cat","volume":"4","author":"Kerr","year":"1961","journal-title":"Exp. Neurol."},{"key":"ref_29","first-page":"761","article-title":"Presynaptic excitability changes produced by conditioning stimulation of primary afferent fibers in trigeminal brain-stem nuclei","volume":"45","author":"Dostrovsky","year":"1981","journal-title":"J. Neurophysiol."},{"key":"ref_30","first-page":"2347","article-title":"The distribution of trigeminovascular afferents in the nonhuman primate brain stem","volume":"120","author":"Goadsby","year":"1997","journal-title":"Brain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cne.902440102","article-title":"Oral and facial representation in the trigeminal principal and rostral spinal nuclei of the cat","volume":"244","author":"Shigenaga","year":"1986","journal-title":"J. Comp. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"S273","DOI":"10.1097\/00006123-200210001-00001","article-title":"The supratentorial cranial space: Microsurgical anatomy and surgical approaches","volume":"51","author":"Rhoton","year":"2002","journal-title":"Neurosurgery"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8183","DOI":"10.1523\/JNEUROSCI.22-18-08183.2002","article-title":"Somatotopic activation in the human trigeminal pain pathway","volume":"22","author":"DaSilva","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/j.pain.0000000000002342","article-title":"Processing of trigeminocervical nociceptive afferent input by neuronal circuity in the upper cervical lamina I","volume":"163","author":"Fernandes","year":"2022","journal-title":"Pain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1146\/annurev-pharmtox-010814-124701","article-title":"Calcitonin gene-related peptide (CGRP): A new target for migraine","volume":"55","author":"Russo","year":"2015","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_36","first-page":"323","article-title":"CGRP antibodies as prophylaxis in migraine","volume":"18","author":"Edvinsson","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1111\/j.1526-4610.2007.00871.x","article-title":"Episodic dural stimulation in awake rats: A model for recurrent headache","volume":"47","author":"Oshinsky","year":"2007","journal-title":"Headache"},{"key":"ref_38","first-page":"1093","article-title":"The trigeminovascular system in humans: Pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation","volume":"22","author":"May","year":"2002","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nrn.2016.68","article-title":"Synaptic plasticity in the anterior cingulate cortex in acute and chronic pain","volume":"17","author":"Bliss","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.pharmthera.2010.01.002","article-title":"Chemokines, neuronal\u2013glial interactions, and central processing of neuropathic pain","volume":"126","author":"Gao","year":"2010","journal-title":"Pharmacol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nrn2533","article-title":"Pathological and protective roles of glia in chronic pain","volume":"10","author":"Milligan","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jpain.2005.09.006","article-title":"Sodium channels and mechanisms of neuropathic pain","volume":"7","author":"Devor","year":"2006","journal-title":"J. Pain"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1172\/JCI43766","article-title":"Central modulation of pain","volume":"120","author":"Ossipov","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_45","first-page":"990","article-title":"Understanding migraine through the lens of maladaptive stress responses: A model disease of allostatic load","volume":"77","author":"Borsook","year":"2013","journal-title":"Neuron"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1159\/000333828","article-title":"Vagoglossopharyngeal neuralgia treated by microvascular decompression and glossopharyngeal rhizotomy: Clinical results of 21 cases","volume":"90","author":"Xiong","year":"2012","journal-title":"Stereotact. Funct. Neurosurg."},{"key":"ref_47","first-page":"172","article-title":"A unified concept of idiopathic orofacial pain: Clinical features","volume":"13","author":"Woda","year":"1999","journal-title":"J. Orofac. Pain"},{"key":"ref_48","unstructured":"Okeson, J.P. (2005). Bell\u2019s Orofacial Pains: The Clinical Management of Orofacial Pain, Quintessence."},{"key":"ref_49","unstructured":"Travell, J.G., and Simons, D.G. (1992). Myofascial Pain and Dysfunction: The Trigger Point Manual, Williams & Wilkins."},{"key":"ref_50","first-page":"153","article-title":"Clinical neurophysiology and quantitative sensory testing in the investigation of orofacial pain and sensory function","volume":"48","year":"2021","journal-title":"J. Oral Rehabil."},{"key":"ref_51","first-page":"171","article-title":"A study of the etiology of referred otalgia","volume":"24","author":"Taziki","year":"2012","journal-title":"Iran. J. Otorhinolaryngol."},{"key":"ref_52","first-page":"16S","article-title":"Cervicogenic headache: A review of diagnostic and treatment strategies","volume":"105","author":"Biondi","year":"2005","journal-title":"J. Am. Osteopath. Assoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3340\/jkns.2012.51.5.281","article-title":"Clinical outcomes of pulsed radiofrequency neuromodulation for the treatment of occipital neuralgia","volume":"51","author":"Choi","year":"2012","journal-title":"J. Korean Neurosurg. Soc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.nec.2018.12.004","article-title":"Occipital Nerve Stimulation","volume":"30","author":"Slavin","year":"2019","journal-title":"Neurosurg. Clin. N. Am."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"T93","DOI":"10.1016\/j.jpain.2016.06.002","article-title":"Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification","volume":"17","author":"Maixner","year":"2016","journal-title":"J. Pain"},{"key":"ref_56","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_57","first-page":"CD006968","article-title":"Local interventions for the management of alveolar osteitis (dry socket)","volume":"9","author":"Daly","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1046\/j.1526-4610.2003.03207.x","article-title":"Atypical odontalgia: A review of the literature","volume":"43","author":"Melis","year":"2003","journal-title":"Headache"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1001\/archinte.164.16.1769","article-title":"Prevalence of migraine in patients with a history of self-reported or physician-diagnosed \u201csinus\u201d headache","volume":"164","author":"Schreiber","year":"2004","journal-title":"Arch. Intern. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_61","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_62","doi-asserted-by":"crossref","first-page":"786.e1","DOI":"10.1016\/j.joms.2020.11.034","article-title":"The Clinical Characteristics and Surgical Treatment of Glossopharyngeal Neuralgia With Pain Radiating to the Innervated Area of the Trigeminal Nerve","volume":"79","author":"Wang","year":"2021","journal-title":"J. Oral. Maxillofac. Surg."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1001\/archotol.1937.00650010656008","article-title":"Elongated styloid process: Report of two cases","volume":"25","author":"Eagle","year":"1937","journal-title":"Arch. Otolaryngol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.clineuro.2017.04.021","article-title":"Eagle syndrome: A comprehensive review","volume":"159","author":"Badhey","year":"2017","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"S91","DOI":"10.1086\/514269","article-title":"Postherpetic neuralgia: The importance of preventing this intractable end-stage disorder","volume":"178","author":"Watson","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_66","first-page":"656","article-title":"Herpes Zoster and Postherpetic Neuralgia: Prevention and Management","volume":"96","author":"Saguil","year":"2017","journal-title":"Am. Fam. Physician"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/S0140-6736(20)32160-7","article-title":"Migraine: Epidemiology and systems of care","volume":"397","author":"Ashina","year":"2021","journal-title":"Lancet"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0196-0709(92)90072-2","article-title":"Referred otalgia","volume":"13","author":"Yanagisawa","year":"1992","journal-title":"Am. J. Otolaryngol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"757","DOI":"10.46747\/cfp.6911757","article-title":"Referred otalgia: Common causes and evidence-based strategies for assessment and management","volume":"69","author":"Ramazani","year":"2023","journal-title":"Can. Fam. Physician"},{"key":"ref_70","unstructured":"Travell, J.G., and Simons, D.G. (1999). Myofascial Pain and Dysfunction: The Trigger Point Manual, Williams & Wilkins. [2nd ed.]."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.berh.2011.01.002","article-title":"Myofascial pain syndromes and their evaluation","volume":"25","author":"Giamberardino","year":"2011","journal-title":"Best. Pract. Res. Clin. Rheumatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0730-725X(96)00383-9","article-title":"Chiari malformation type I: A new MRI classification","volume":"15","author":"Amer","year":"1997","journal-title":"Magn. Reson. Imaging"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.3174\/ajnr.A5354","article-title":"MR Neurography of Greater Occipital Nerve Neuropathy: Initial Experience in Patients with Migraine","volume":"38","author":"Hwang","year":"2017","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1533-2500.2006.00068.x","article-title":"Occipital nerve blockade for cervicogenic headache: A double-blind randomized controlled clinical trial","volume":"6","author":"Naja","year":"2006","journal-title":"Pain Pract."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1097\/AAP.0b013e3181d24713","article-title":"Pulsed radiofrequency for the treatment of occipital neuralgia: A prospective study with 6 months of follow-up","volume":"35","author":"Vanelderen","year":"2010","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1023\/A:1026119331193","article-title":"A six-item short-form survey for measuring headache impact: The HIT-6","volume":"12","author":"Kosinski","year":"2003","journal-title":"Qual. Life Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Mustafa, M.S., Bin Amin, S., Kumar, A., Shafique, M.A., Fatima Zaidi, S.M., Arsal, S.A., Rangwala, B.S., Iqbal, M.F., Raja, A., and Haseeb, A. (2024). Assessing the effectiveness of greater occipital nerve block in chronic migraine: A systematic review and meta-analysis. BMC Neurol., 24.","DOI":"10.1186\/s12883-024-03834-6"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1468-2982.2007.01272.x","article-title":"Occipital nerve stimulation for chronic headache\u2014Long-term safety and efficacy","volume":"27","author":"Schwedt","year":"2007","journal-title":"Cephalalgia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1177\/0333102411412086","article-title":"Treatment of refractory chronic cluster headache by chronic occipital nerve stimulation","volume":"31","author":"Fontaine","year":"2011","journal-title":"Cephalalgia"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/ner.12208","article-title":"The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: The Neuromodulation Appropriateness Consensus Committee","volume":"17","author":"Deer","year":"2014","journal-title":"Neuromodulation"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S1474-4422(19)30414-4","article-title":"Long-term safety and efficacy of closed-loop spinal cord stimulation to treat chronic back and leg pain (Evoke): A double-blind, randomised, controlled trial","volume":"19","author":"Mekhail","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1111\/j.1468-1331.2010.02969.x","article-title":"EFNS guidelines on neuropathic pain assessment: Revised 2009","volume":"17","author":"Cruccu","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1093\/brain\/awp035","article-title":"Motor cortex stimulation for the treatment of refractory peripheral neuropathic pain","volume":"132","author":"Lefaucheur","year":"2009","journal-title":"Brain"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1227\/NEU.0000000000001353","article-title":"Clinical Significance of Invasive Motor Cortex Stimulation for Trigeminal Facial Neuropathic Pain Syndromes","volume":"79","author":"Rasche","year":"2016","journal-title":"Neurosurgery"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.pain.2005.12.006","article-title":"Motor cortex stimulation for long-term relief of chronic neuropathic pain: A 10 year experience","volume":"121","author":"Rasche","year":"2006","journal-title":"Pain"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.clineuro.2014.05.026","article-title":"Supraspinal stimulation for treatment of refractory pain","volume":"123","author":"Parmar","year":"2014","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1227\/NEU.0000000000000321","article-title":"Targeting the affective component of chronic pain: A case series of deep brain stimulation of the anterior cingulate cortex","volume":"74","author":"Boccard","year":"2014","journal-title":"Neurosurgery"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.clinph.2019.11.002","article-title":"Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014\u20132018)","volume":"131","author":"Lefaucheur","year":"2020","journal-title":"Clin. Neurophysiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/head.13586","article-title":"Neuromodulation for the Acute and Preventive Therapy of Migraine and Cluster Headache","volume":"59","author":"Ailani","year":"2019","journal-title":"Headache"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1037\/0033-2909.133.4.581","article-title":"The biopsychosocial approach to chronic pain: Scientific advances and future directions","volume":"133","author":"Gatchel","year":"2007","journal-title":"Psychol. Bull."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/ncpneuro0530","article-title":"Technology insight: Noninvasive brain stimulation in neurology\u2014Perspectives on the therapeutic potential of rTMS and tDCS","volume":"3","author":"Fregni","year":"2007","journal-title":"Nat. Clin. Pract.  Neurol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1016\/j.neuroimage.2007.05.062","article-title":"Motor cortex stimulation for neuropathic pain: From phenomenology to mechanisms","volume":"37","author":"Peyron","year":"2007","journal-title":"Neuroimage"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1111\/head.12896","article-title":"Non-Invasive Vagus Nerve Stimulation for the Acute Treatment of Cluster Headache: Findings From the Randomized, Double-Blind, Sham-Controlled ACT1 Study","volume":"56","author":"Silberstein","year":"2016","journal-title":"Headache"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1177\/03331024211068813","article-title":"Non-invasive vagus nerve stimulation for prevention of migraine: The multicenter, randomized, double-blind, sham-controlled PREMIUM II trial","volume":"42","author":"Najib","year":"2022","journal-title":"Cephalalgia"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1586\/14737175.2013.846218","article-title":"Losses and gains: Chronic pain and altered brain morphology","volume":"13","author":"Borsook","year":"2013","journal-title":"Expert. Rev. Neurother."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/s41467-022-28473-8","article-title":"Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain","volume":"13","author":"Tansley","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1002\/glia.24133","article-title":"Sex-specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury","volume":"70","author":"Fiore","year":"2022","journal-title":"Glia"},{"key":"ref_98","first-page":"290","article-title":"Motor cortex stimulation for central and peripheral deafferentation pain","volume":"128","author":"Saitoh","year":"2007","journal-title":"Pain"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"698","DOI":"10.3171\/JNS\/2008\/108\/4\/0698","article-title":"Efficacy of motor cortex stimulation in the treatment of neuropathic pain: A randomized double-blind trial","volume":"108","author":"Velasco","year":"2008","journal-title":"J. Neurosurg."},{"key":"ref_100","first-page":"678","article-title":"Peripheral nerve stimulation for treatment of occipital neuralgia and other chronic headaches","volume":"17","author":"Johnson","year":"2014","journal-title":"Neuromodulation"},{"key":"ref_101","first-page":"891","article-title":"Stimulation of the auriculotemporal nerve in patients with refractory cluster headache","volume":"35","author":"Slotty","year":"2015","journal-title":"Cephalalgia"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.2174\/0929867323666160607120124","article-title":"Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain","volume":"23","author":"Mika","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1097\/AJP.0000000000000415","article-title":"Evaluation of Chronic Pain Using Magnetic Resonance (MR) Neuroimaging Approaches: What the Clinician Needs to Know","volume":"33","author":"Kumbhare","year":"2017","journal-title":"Clin. J. 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