Sarchielli Paola, Mancini Maria Luisa, Floridi Alessandro, Coppola Francesca, Rossi Cristiana, Nardi Katiuscia, Acciarresi Monica, Pini Luigi Alberto, Calabresi Paolo
Neurologic Clinic, Department of Medical and Surgical Specialties and Public Health, University of Perugia, Perugia, Italy.
J Pain. 2007 Sep;8(9):737-45. doi: 10.1016/j.jpain.2007.05.002. Epub 2007 Jul 5.
All data obtained in experimental animal pain models support the role of nerve growth factor (NGF) as a putative candidate intervening in the pathogenesis of chronic pain, including chronic daily headache (CDH). Few studies have been carried out to establish its role in maintaining pain states in humans. The present study was aimed at investigating cerebrospinal fluid (CSF) levels of NGF and brain-derived neurotrophic factor (BDNF), both measured by sensitive immunoassay, in 20 chronic migraine (CM) patients and 20 patients affected by primary fibromyalgia syndrome (PFMS), compared with those of 20 age-matched control subjects. Significantly higher levels of both neurotrophins and glutamate were found. A significantly positive correlation emerged between CSF values of BDNF and those of NGF (r = .61, P < .001; r = .53, P < .01) and glutamate (r = .44, P < .02; r = .51, P < .01) in CM and PFMS patients, respectively. These findings suggest the possibility of a NGF-mediated up-regulation of BDNF involved in the pathophysiological events underlying long-term neuroplastic changes in persistent chronic painful conditions, such as CM and fibromyalgia. NGF might indirectly exert its effect through enhancing glutamatergic transmission via BDNF. The above mechanisms could account for sustained central sensitization in both chronic pain states.
This article presents findings of higher NGF and BDNF levels correlated to increased glutamate levels in the CSF of both chronic migraine and fibromyalgia patients. This opens new insights into the pathogenic mechanisms of chronic pain and offers clinicians new therapeutic perspectives targeting the above mechanisms in both painful disorders.
在实验动物疼痛模型中获得的所有数据均支持神经生长因子(NGF)作为一种可能参与慢性疼痛(包括慢性每日头痛,即CDH)发病机制的候选因子的作用。很少有研究探讨其在维持人类疼痛状态中的作用。本研究旨在通过灵敏的免疫测定法,检测20例慢性偏头痛(CM)患者和20例原发性纤维肌痛综合征(PFMS)患者脑脊液(CSF)中NGF和脑源性神经营养因子(BDNF)的水平,并与20例年龄匹配的对照受试者进行比较。结果发现,两种神经营养因子和谷氨酸水平均显著升高。在CM和PFMS患者中,BDNF的CSF值与NGF的CSF值(r = 0.61,P < 0.001;r = 0.53,P < 0.01)以及谷氨酸的CSF值(r = 0.44,P < 0.02;r = 0.51,P < 0.01)之间分别呈现显著正相关。这些发现提示,在持续性慢性疼痛状态(如CM和纤维肌痛)中,NGF介导的BDNF上调可能参与了长期神经可塑性变化的病理生理过程。NGF可能通过BDNF增强谷氨酸能传递而间接发挥作用。上述机制可能解释了两种慢性疼痛状态下持续的中枢敏化现象。
本文呈现了慢性偏头痛和纤维肌痛患者脑脊液中NGF和BDFDNF水平升高且与谷氨酸水平升高相关的研究结果。这为慢性疼痛的发病机制提供了新的见解,并为临床医生针对这两种疼痛性疾病的上述机制提供了新的治疗视角。