title: Increased vascular penetration and nerve growth in the meniscus: a potential source of pain in osteoarthritis.
abstract: OBJECTIVE
  Meniscal damage is a recognised feature of knee osteoarthritis (OA), although its clinical relevance remains uncertain. This study describes vascular penetration and nerve growth in human menisci, providing a potential mechanism for the genesis of pain in knee OA.
  
  
  METHODS
  Menisci obtained post mortem were screened on the basis of high or low macroscopic tibiofemoral chondropathy as a measure of the presence and degree of OA. Forty cases (20 per group) were selected for the study of meniscal vascularity, and 16 (eight per group) for the study of meniscal innervation. Antibodies directed against α-actin and calcitonin gene-related peptide (CGRP) were used to localise blood vessels and nerves by histochemistry. Image analysis was used to compare vascular and nerve densities between groups. Data are presented as median (IQR).
  
  
  RESULTS
  Menisci from knees with high chondropathy displayed degeneration of collagen bundles in their outer regions, which were more vascular than the inner regions, with an abrupt decrease in vascularity at the fibrocartilage junction. Vascular densities were increased in menisci from the high compared with low chondropathy group both in the synovium (3.8% (IQR 2.6-5.2), 2.0% (IQR 1.4-2.9), p=0.002) and at the fibrocartilage junction (2.3% (IQR 1.7-3.1), 1.1% (IQR 0.8-1.9), p=0.003), with a greater density of perivascular sensory nerve profiles in the outer region (high chondropathy group, 144 nerve profiles/mm(2) (IQR 134-189); low chondropathy group, 119 nerve profiles/mm(2) (IQR 104-144), p=0.049).
  
  
  CONCLUSIONS
  Tibiofemoral chondropathy is associated with altered matrix structure, increased vascular penetration, and increased sensory nerve densities in the medial meniscus. The authors suggest therefore that angiogenesis and associated sensory nerve growth in menisci may contribute to pain in knee OA.
authors.affiliation: Academic Rheumatology, Arthritis Research UK Pain Centre, University of Nottingham, Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham NG5 1PB, UK. mbxsa1@nottingham.ac.uk
authors.forename: Sadaf
authors.initials: S
authors.lastname: Ashraf
authors.forename: Helen
authors.initials: H
authors.lastname: Wibberley
authors.forename: Paul Ian
authors.initials: PI
authors.lastname: Mapp
authors.forename: Roger
authors.initials: R
authors.lastname: Hill
authors.forename: Deborah
authors.initials: D
authors.lastname: Wilson
authors.forename: David Andrew
authors.initials: DA
authors.lastname: Walsh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008592:Menisci, Tibial / Q000098:blood supply* / Q000294:innervation / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000150:complications* / Q000473:pathology; D020370:Osteoarthritis, Knee / Q000150:complications* / Q000473:pathology; D010146:Pain / Q000209:etiology*; D011984:Sensory Receptor Cells / Q000473:pathology; D012720:Severity of Illness Index