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慢性肌腱疼痛:无化学性炎症迹象,但神经递质谷氨酸浓度高。对治疗有何启示?

Chronic tendon pain: no signs of chemical inflammation but high concentrations of the neurotransmitter glutamate. Implications for treatment?

作者信息

Alfredson Håkan, Lorentzon Ronny

机构信息

Umeå University, Department of Surgical and Perioperative Science, Centre for Musculoskeletal Research, National Institute for Working Life, Sweden.

出版信息

Curr Drug Targets. 2002 Feb;3(1):43-54. doi: 10.2174/1389450023348028.

DOI:10.2174/1389450023348028
PMID:11899264
Abstract

Chronic musculo-tendinous pain syndromes are relatively common and associated with very high socio-economic costs. Their aetiology and pathogenesis are still unknown. In the athletic population, chronic tendon pain is most often seen among recreational male and female athletes in the age group between 30-60 years, and is considered to be associated with overuse of the aged tendon. Treatment is known to be difficult. In general, these chronic painful conditions have been considered to include an inflammatory component, and the nomenclature used (tendinitis, tendonitis) most often implies an inflammatory involvement. Despite that tendon biopsies have shown an absence of inflammatory cell infiltration, anti-inflammatory agents (NSAID'S, corticosteroidal injections) are most often included in the treatment. Our research has been focused on chronic painful conditions in the Achilles-, patellar-, and extensor carpi radialis brevis (ECRB)-tendons. We have demonstrated, for the first time, that it is possible to use the microdialysis technique for in vivo investigations of human tendons, and that the excitatory neurotransmitter glutamate exists in human tendons. We have identified and measured the concentrations of prostaglandin E2 (PGE2) in tendons as well. The results showed that chronic painful tendinosis (Achilles-, patellar-, ECRB-) had significantly higher concentrations of glutamate, but not PGE2, as compared to the pain-free normal tendons. With the use of immunohistochemical analyses and enzyme histochemistry of human Achilles- and patellar tendon biopsies, we have also, for the first time demonstrated that glutamate NMDARI-immunoreaction was present in nerve structures. These findings altogether, indicate that glutamate might be involved in chronic tendon pain, and further emphasizes that there is no chemical inflammation (normal PGE2 levels) in the chronic stage of these relatively common so-called tendinopathies. The findings of glutamate and it's NMDARI-receptors might have implications for treatment and be a potential target for drugs.

摘要

慢性肌肉肌腱疼痛综合征相对常见,且社会经济成本极高。其病因和发病机制尚不清楚。在运动员群体中,慢性肌腱疼痛最常见于30至60岁的男女业余运动员中,被认为与老化肌腱的过度使用有关。已知治疗困难。一般来说,这些慢性疼痛病症被认为包括炎症成分,使用的术语(肌腱炎、腱鞘炎)最常暗示炎症参与。尽管肌腱活检显示没有炎症细胞浸润,但治疗中最常使用抗炎药(非甾体抗炎药、皮质类固醇注射)。我们的研究集中在跟腱、髌腱和桡侧腕短伸肌(ECRB)肌腱的慢性疼痛病症上。我们首次证明,可以使用微透析技术对人体肌腱进行体内研究,并且人体肌腱中存在兴奋性神经递质谷氨酸。我们还鉴定并测量了肌腱中前列腺素E2(PGE2)的浓度。结果表明,与无痛的正常肌腱相比,慢性疼痛性肌腱病(跟腱、髌腱、ECRB)中的谷氨酸浓度显著更高,但PGE2浓度并非如此。通过对人体跟腱和髌腱活检进行免疫组织化学分析和酶组织化学,我们还首次证明神经结构中存在谷氨酸NMDARI免疫反应。这些发现共同表明,谷氨酸可能与慢性肌腱疼痛有关,并进一步强调在这些相对常见的所谓肌腱病的慢性阶段不存在化学炎症(PGE2水平正常)。谷氨酸及其NMDARI受体的发现可能对治疗有影响,并且可能成为药物的潜在靶点。

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