Cartilage pp 191-227 | Cite as

The Sensory and Sympathetic Nervous System in Cartilage Physiology and Pathophysiology

  • Susanne GrässelEmail author
  • Rainer H. Straub
  • Zsuzsa Jenei-Lanzl


The peripheral nervous system is critically involved in metabolism of joint tissue and intervertebral disks (IVD). Nerve fibers of sympathetic and sensory origin innervate synovial tissue and subchondral bone of diarthrodial joints. In pathophysiological situations as in osteoarthritis (OA), rheumatoid arthritis (RA), and IVD degeneration, innervation patterns of sympathetic and sensory nerve fibers are partly altered in joint tissue and IVD.

Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters allowing response to neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts, bone cells, and different types of chondrocytes, which express distinct subtypes of adrenoceptors, receptors for vasoactive intestinal peptide (VIP), for substance P (SP), and calcitonin gene-related peptide (CGRP). Some of these cell types even synthesize neuropeptides such as SP, and they are positive for tyrosine hydroxylase (TH), the rate limiting enzyme for biosynthesis of catecholamines. During endochondral ossification in embryonic limb development, sensory and sympathetic neurotransmitters modulate osteo-chondrogenic differentiation of mesenchymal progenitor cells, vascularization, and matrix differentiation indicating a distinct role in skeletal growth and possible limb regeneration processes. In adults, sensory and sympathetic neurotransmitters are involved in pathology of inflammatory diseases as rheumatoid arthritis which manifests mainly in joints. In addition, they might play a role in pathogenesis of a priori degenerative joint disorders, as osteoarthritis and intervertebral disk degeneration.

Altogether it became evident that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for proper limb formation during embryonic skeletal growth. In adults, they modulate articular cartilage, subchondral bone and synovial tissue homeostasis, and physiological and pathophysiological conditions, in addition to their classical neurological features.


Nerve Fiber Nerve Growth Factor Articular Cartilage Vasoactive Intestinal Peptide Annulus Fibrosus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors are supported by the DFG grants to SG (GR 1301-19) and to ZJL (JE 642/4-1), both subprojects of FOR 2407-1.


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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Susanne Grässel
    • 1
    Email author
  • Rainer H. Straub
    • 2
  • Zsuzsa Jenei-Lanzl
    • 3
  1. 1.Experimental Orthopaedics, Department of Orthopaedic SurgeryUniversity of RegensburgRegensburgGermany
  2. 2.Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine IUniversity of RegensburgRegensburgGermany
  3. 3.Dr. Rolf M. Schwiete Research Unit for OsteoarthritisOrthopaedic University Hospital Friedrichsheim gGMBH Johann Wolfgang Goethe-UniversityFrankfurt a.M.Germany

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