Presence of NGF and its receptor TrkA in degenerative lumbar facet joint specimens

Abstract

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.

Characterization of subchondral bone histopathology of facet joint osteoarthritis in lumbar spinal stenosis

“…Lumbar facet joint osteoarthritis may be a causative of clinical symptoms, such as low back pain, in degenerative spine diseases including lumbar spinal stenosis. Due to its clinical relevance, several studies have been performed to characterize the pathological changes that occur in osteoarthritic facet joint tissues including cartilage, capsule, and synovium . Histopathological changes in subchondral bone and marrow tissues have been relatively understudied.…”

“…Due to its clinical relevance, several studies have been performed to characterize the pathological changes that occur in osteoarthritic facet joint tissues including cartilage, capsule, and synovium. 16,[24][25][26][27][28] Histopathological changes in subchondral bone and marrow tissues have been relatively understudied. In this FACET JOINT OSTEOARTHRITIS IN SPINAL STENOSIS study, we identified extensive de novo bone formation and macrophage-rich tissue infiltration of subchondral bone marrow as major histopathological characteristics of facet joint osteoarthritis in patients with lumbar spinal stenosis.…”

“…Several studies have investigated the degree of innervation and expression of pain mediators in degenerative lumbar facet joint tissues. 16,24,26,28 Nerve growth factor 16,24 and substance P 28 have been shown to be present in facet joint capsules and subchondral marrow tissues of osteoarthritic facet joints. Interestingly, the rate of innervation by PGP9.5 fibres differed between ligamentum flavum (72%), facet joint capsule (70%) and intervertebral disc (20%).…”

Intra-articular nerve growth factor regulates development, but not maintenance, of injury-induced facet joint pain & spinal neuronal hypersensitivity

“…Anti-NGF antibody treatment alleviates pain from inflammation and nerve injury in rat models 17,18 , and systemic anti-NGF reduces osteoarthritic joint pain 19 , supporting NGF’s role in joint pain. NGF and its high-affinity receptor, trkA, have been identified in osteoarthritic joints and degenerative facets 11,20–22 . Although studies collectively suggest intra-articular NGF contributes to degenerative joint pain, its contribution to injury -induced facet pain is unknown.…”

Local Administration of a Synthetic Cell-Penetrating Peptide Antagonizing TrkA Function Suppresses Inflammatory Pain in Rats

“…Increased expression of either NGF or its high-affinity receptor TrkA, which exacerbates pain states, is reported in inflammatory tissues, including burn-injured tissue (3,4), postoperative surgical sites (5,6), and human degenerative lumbar facet joints (7). Local injection of complete Freund's adjuvant (CFA), which is utilized for the inflammatory pain model, also increases NGF expression in the skin (8).…”