Raguž Marina, Tarle Marko, Hat Koraljka, Salarić Ivan, Marčinković Petar, Bičanić Ivana, Lazić Mosler Elvira, Lukšić Ivica, Marinović Tonko, Chudy Darko
Department of Neurosurgery, Dubrava University Hospital, 10000 Zagreb, Croatia.
School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia.
Life (Basel). 2025 Sep 17;15(9):1457. doi: 10.3390/life15091457.
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.
头颈部难治性神经性疼痛仍然是一项重大的临床挑战，尤其是当疼痛通过颈三叉神经复合体（CTC）介导时，该复合体是一个独特的解剖枢纽，整合了三叉神经和上颈部的伤害性输入。本叙述性综述综合了神经解剖学、病理生理学和临床证据，为诊断和管理提供了一个统一的框架。通过对PubMed、Scopus和Web of Science进行结构化检索，确定了针对CTC介导疼痛的英文临床和机制研究，排除了病例报告，除非其具有机制性信息。我们提出了多维难治性标准，该标准整合了药物无反应、介入策略失败和客观功能损害。目前的治疗方法包括药物治疗、外周干预（神经阻滞、射频消融）以及多个网络层面的神经调节（枕神经刺激、脊髓刺激、运动皮层刺激、深部脑刺激）。诸如重复经颅磁刺激（rTMS）、经颅直流电刺激（tDCS）和迷走神经刺激等非侵入性方法正在兴起，但仍处于研究阶段。成像和神经生理学生物标志物的进展现在使得在检测CTC功能障碍和定制治疗方面具有更高的精度。通过结合解剖学精度、机制性见解和多学科策略，本综述提出了一个临床可行的难治性定义，并支持一种基于机制的逐步治疗方法。CTC成为难治性头颈部疼痛诊断和治疗策略的一个可靶向枢纽。
