Grading of monosodium iodoacetate-induced osteoarthritis reveals a concentration-dependent sensitization of nociceptors in the knee joint of the rat

Neurosci Lett. 2009 Nov 13;465(2):184-8. doi: 10.1016/j.neulet.2009.08.063. Epub 2009 Aug 27.


Osteoarthritis (OA) is a degenerative joint disease characterized by joint pain for which there is currently no effective treatment. Previous studies have found that intra-articular injection of monosodium iodoacetate (MIA) caused a dose-dependent destruction of rat knees with concomitant increased pain. In this study, varying degrees of OA were induced by intra-articular injection of 0.1 mg, 0.3 mg and 3 mg MIA. Electrophysiological recordings were made from knee joint primary afferents in response to rotation of the joint and firing frequencies were determined and compared to saline-injected control joints. The analgesic effect of local application of the classic non-steroidal anti-inflammatory drug (NSAID) diclofenac (0.1 mg/0.1 ml bolus) was also determined in each group. Joint afferent firing frequency was significantly enhanced in OA knees compared to saline injected control joints and the magnitude of this sensitization showed a direct relationship with increasing dose of MIA. Diclofenac reduced nociception significantly in the 3 mg MIA treated joint, but had no effect on nerve mechanosensitivity in rats with milder OA. This study shows for the first time that MIA produces a graded sensitization of joint nociceptors making this a useful model for the study of pain mechanisms in joints with progressive OA severity. The anti-nociceptive effect of diclofenac further indicates that the MIA model offers an attractive means of objectively testing potential therapeutic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Alkylating Agents / administration & dosage
  • Alkylating Agents / adverse effects*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Diclofenac / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Iodoacetates / administration & dosage
  • Iodoacetates / adverse effects*
  • Knee Joint / drug effects
  • Knee Joint / innervation
  • Knee Joint / physiopathology*
  • Male
  • Movement / drug effects
  • Movement / physiology
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / physiology
  • Nociceptors / drug effects
  • Nociceptors / physiology*
  • Osteoarthritis, Knee / chemically induced*
  • Osteoarthritis, Knee / drug therapy
  • Osteoarthritis, Knee / physiopathology*
  • Pain / chemically induced
  • Pain / drug therapy
  • Pain / physiopathology
  • Physical Stimulation
  • Rats
  • Rats, Wistar
  • Rotation


  • Alkylating Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Iodoacetates
  • Diclofenac