Presence of NGF and its receptor TrkA in degenerative lumbar facet joint specimens
Presence of NGF and its receptor TrkA in degenerative lumbar facet joint specimens
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DOI：
10.1007/s00586-009-0994-9
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发表时间：
2009-06-01
影响因子：
2.8
通讯作者：
Murena, L.
中科院分区：
文献类型：
--
作者：
Surace, M. F.;Prestamburgo, D.;Murena, L.
在一项初步研究中，在几张退行性腰椎小关节和周围软组织的载玻片上，光学显微镜证实了神经末梢的反复存在。本研究的目的是用免疫荧光法证实NGF（神经生长因子）及其受体TrkA（酪氨酸激酶受体）的存在。从10例因退行性疾病而接受手术治疗的患者的腰椎关节突关节处采集关节周围组织。7例女性（1例双侧），2例男性，手术时平均年龄为72岁（67-80岁）。2例L3-L4, 7例L4-L5（1例双侧）。所有标本用福尔马林固定，脱水，石蜡包封。从每个标本中获得四张载玻片。两张载玻片用于寻找NGF：一张用特异性抗体处理并标记FITC（异硫氰酸荧光素偶联），另一张载玻片用于对照。它暴露于FITC，但事先没有暴露于特异性抗体。在另外两张载玻片上重复同样的步骤，重复寻找具有特异性抗体的Trka。最后在荧光显微镜下对所有载玻片进行研究。对这些标本的分析显示，在所有病例中都存在神经营养因子（NGF）及其自身受体（TrkA）：在荧光显微镜下可以看到标本与FITC标记的特异性抗体之间的免疫组织化学反应，但在仅用FITC治疗的对照病例中没有一例。NGF是由乳腺细胞、成纤维细胞和其他参与炎症过程的细胞类型释放的。外周神经生长因子的水平在炎症过程中增加，而外源性神经生长因子的管理对大鼠具有过敏作用，并在人类中产生肌肉疼痛。此外。在人类和哺乳动物中，神经生长因子通常对热刺激产生超敏反应。大量证据表明，由NGF及其高亲和力受体TrkA组成的系统在主要形式的“持续性”疼痛的分子过程中起着重要作用。这提示了抗体可能的治疗领域，该抗体可以阻断NGF/TrkA系统，以调节慢性炎症期间伤害性神经元动作电位的频率和持续时间。本研究表明，从退行性小关节收集的标本中存在NGF和TrkA，表明可以使用特定分子来调节退行性腰椎患者的慢性疼痛。
In a preliminary study, the recurrent presence of nervous terminations was demonstrated with optical microscopy in several slides of degenerative lumbar facet joints and surrounding soft tissues. The purpose of this study was to prove the presence of NGF (nerve growth factor) and its receptor TrkA (tyrosine kinase receptor) with immunofluorescence. The peri/articular tissues were harvested from the lumbar facet joints of ten patients surgically treated for degenerative diseases. There were seven females (one bilateral) and two males whose mean age at surgery was 72 years (range, 67-80 years). The affected levels were L3-L4 in two cases and L4-L5 in seven cases (one bilateral). All specimens were fixed in formalin, dehydrated and enclosed in paraffin. From each specimen, four slides were obtained. Two slides were employed for the search of NGF: one was treated with specific antibodies and marked with FITC (fluorescein isothiocyanate conjugated), and the second slide was for control purposes. It was exposed to FITC, but without prior exposure to the specific antibody. The same procedure was repeated to obtain on two more slides, to repeat the search for Trka with specific antibodies. All the slides were finally studied on a fluoromicroscope. The analysis of these specimens revealed the presence of the neurotrophin (NGF) and its own receptor (TrkA) in all cases: the immunohistochemical reaction between the specimens and the specific antibodies marked with FITC was seen under fluoromicroscopy, but in none of the control cases treated with FITC only. NGF is released by mastocytes, fibroblasts and other cell types involved in the inflammatory processes. The level of peripheral NGF is increased in inflammatory processes, while the administration of exogenous NGF has a hyperalgesic effect on rats and produces muscular pain in humans. Furthermore. NGF produces hypersensitization to heat stimulation in humans and mammals in general. There is considerable evidence showing that the system constituted by the NGF and its high-affinity receptor TrkA plays a fundamental role in the molecular processes underlying the main forms of "persistent" pain. This indicates a possible therapeutic area for the antibodies that could block the NGF/TrkA system, in order to modulate the frequency and the duration of the action potential of nociceptive neurons during chronic inflammation. This study demonstrated the presence of NGF and TrkA in specimens collected from degenerative facet joints, suggesting that specific molecules could be used in order to modulate chronic pain in patients with degenerative lumbar spine.