Distribution of substance-P nerves inside the infrapatellar fat pad and the adjacent synovial tissue: a neurohistological approach to anterior knee pain syndrome

Arch Orthop Trauma Surg. 2005 Nov;125(9):592-7. doi: 10.1007/s00402-005-0796-4.


Introduction: The purpose of the study was to determine the distribution and number of nerves inside the infrapatellar fat pad and the adjacent synovium, in particular with regards to nociceptive substance-P nerves.

Materials and methods: The infrapatellar fat pad of the knee was resected from 21 patients (4 male, 17 female, mean age 69 years) during the course of standard total knee arthroplasty operations performed in our clinic. The fat pad was dissected into five standardized segments, fixed in formalin and embedded in paraffin. Immunohistochemical techniques using antibodies against S-100 protein and substance-P (SP) were employed to determine and specify the nerves.

Results: Studying all the detectable nerves present in 50 observation fields (200-fold magnification), we found an average of 106 S-100 versus 25 SP nerves (24%) in the synovium and 27 S-100- versus 7 SP nerves (26%) in the interior of the fat pad. The total nerve count was significantly (P < 0.001) higher in the synovium than in the fat pad for both marker types. The number of S-100 nerves was significantly (P < 0.05) higher in the central and lateral segments of the fat pad, while SP nerves were equally distributed throughout all segments of the fat-pad. SP nerves were significantly more frequently associated with blood vessels inside the fat pad (43%, P < 0.05) than in the synovial tissue (28%).

Conclusion: The occurrence and distribution of SP nerves inside the infrapatellar fat pad suggest a nociceptive function and a neurohistological role in anterior knee pain syndrome. The data support the hypothesis that a neurogenous infection of the infrapatellar fat pad could contribute to anterior knee pain syndrome.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arthralgia
  • Female
  • Humans
  • Immunohistochemistry
  • Knee Joint / innervation*
  • Male
  • Middle Aged
  • S100 Proteins / metabolism
  • Substance P / metabolism*
  • Syndrome
  • Synovial Membrane / innervation*


  • S100 Proteins
  • Substance P