Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain model

Hee Jeong Im, Jae Sung Kim, Xin Li, Naomi Kotwal, Dale R. Sumner, Andre J van Wijnen, Francesca J. Davis, Dongyao Yan, Brett Levine, James L. Henry, Jacques Desevré, Jeffrey S. Kroin

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Objective. To verify the biologic links between progressive cellular and structural alterations within knee joint components and development of symptomatic chronic pain that are characteristic of osteoarthritis (OA), and to investigate the molecular basis of alterations in nociceptive pathways caused by OA-induced pain. Methods. An animal model of knee joint OA pain was generated by intraarticular injection of mono-iodoacetate (MIA) in Sprague-Dawley rats, and symptomatic pain behavior tests were performed. Relationships between development of OA with accompanying pain responses and gradual alterations in cellular and structural knee joint components (i.e., cartilage, synovium, meniscus, subchondral bone) were examined by histologic and immunohistologic analysis, microscopic examination, and microfocal computed tomography. Progressive changes in the dynamic interrelationships between peripheral knee joint tissue and central components of nociceptive pathways caused by OA-induced pain were examined by investigating cytokine production and expression in sensory neurons of the dorsal root ganglion and spinal cord. Results. We observed that structural changes in components of the peripheral knee joint correlate with alterations in the central compartments (dorsal root ganglia and the spinal cord) and symptomatic pain assessed by behavioral hyperalgesia. Our comparative gene expression studies revealed that the pain pathways in MIA-induced knee OA may overlap, at least in part, with neuropathic pain mechanisms. Similar results were also observed upon destabilization of the knee joint in the anterior cruciate ligament transection and destabilization of the medial meniscus models of OA. Conclusion. Our results indicate that MIA-induced joint degeneration in rats generates an animal model that is suitable for mechanistic and pharmacologic studies on nociceptive pain pathways caused by OA, and provide key in vivo evidence that OA pain is caused by central sensitization through communication between peripheral OA nociceptors and the central sensory system. Furthermore, our data suggest a mechanistic overlap between OA-induced pain and neuropathic pain.

Original languageEnglish (US)
Pages (from-to)2995-3005
Number of pages11
JournalArthritis and Rheumatism
Volume62
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

Fingerprint

Sensory Receptor Cells
Osteoarthritis
Knee Joint
Pain
Iodoacetates
Knee Osteoarthritis
Spinal Ganglia
Neuralgia
Spinal Cord
Animal Models
Central Nervous System Sensitization
Tibial Meniscus
Nociceptive Pain
Intra-Articular Injections
Nociceptors
Synovial Membrane
Anterior Cruciate Ligament
Hyperalgesia
Arthralgia
Chronic Pain

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Im, H. J., Kim, J. S., Li, X., Kotwal, N., Sumner, D. R., van Wijnen, A. J., ... Kroin, J. S. (2010). Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain model. Arthritis and Rheumatism, 62(10), 2995-3005. https://doi.org/10.1002/art.27608

Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain model. / Im, Hee Jeong; Kim, Jae Sung; Li, Xin; Kotwal, Naomi; Sumner, Dale R.; van Wijnen, Andre J; Davis, Francesca J.; Yan, Dongyao; Levine, Brett; Henry, James L.; Desevré, Jacques; Kroin, Jeffrey S.

In: Arthritis and Rheumatism, Vol. 62, No. 10, 10.2010, p. 2995-3005.

Research output: Contribution to journalArticle

Im, HJ, Kim, JS, Li, X, Kotwal, N, Sumner, DR, van Wijnen, AJ, Davis, FJ, Yan, D, Levine, B, Henry, JL, Desevré, J & Kroin, JS 2010, 'Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain model', Arthritis and Rheumatism, vol. 62, no. 10, pp. 2995-3005. https://doi.org/10.1002/art.27608
Im, Hee Jeong ; Kim, Jae Sung ; Li, Xin ; Kotwal, Naomi ; Sumner, Dale R. ; van Wijnen, Andre J ; Davis, Francesca J. ; Yan, Dongyao ; Levine, Brett ; Henry, James L. ; Desevré, Jacques ; Kroin, Jeffrey S. / Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain model. In: Arthritis and Rheumatism. 2010 ; Vol. 62, No. 10. pp. 2995-3005.
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