title: Regulation of pain sensitivity in experimental osteoarthritis by the endogenous peripheral opioid system.
abstract: OBJECTIVE
  OA is the most common joint disease, affecting 10-15% of people over 60 years of age. However, up to 40% of individuals with radiologic damage are asymptomatic. The purpose of this study was to assess the role of the endogenous opioid system in delaying the onset of pain in a murine model of osteoarthritis (OA).
  
  
  METHODS
  Osteoarthritis was induced by transection of the medial meniscotibial ligament. Pain was assessed by monitoring weight distribution and activity. At various times postsurgery, the opioid receptor antagonists naloxone or peripherally restricted naloxone methiodide were administered, and pain was assessed. Levels of the micro-opioid receptor were assessed in the nerves innervating the joint by real-time reverse transcription-polymerase chain reaction analysis.
  
  
  RESULTS
  As in human disease, significant joint damage occurred in mice before the onset of pain. To assess whether delayed pain was partly the result of increased endogenous opioid function, naloxone or naloxone methiodide was administered. Both opioid receptor antagonists led to pain onset 4 weeks earlier than in vehicle-treated mice, indicating a role of the peripheral opioid system in masking OA pain. The expression of the micro-opioid receptor in the peripheral nerves supplying the joint was transiently increased in naloxone-responsive mice.
  
  
  CONCLUSIONS
  These findings indicate that a temporal induction of micro-opioid receptors in the early stages of OA delays the onset of pain. This is of clinical relevance and may contribute to the assessment of patients presenting with pain late in the disease. Furthermore, it may point to a mechanism by which the body blocks pain perception in moderate states of tissue damage, allowing an increased chance of survival.
authors.affiliation: Kennedy Institute of Rheumatology, Imperial College London, London, UK. j.inglis@imperial.ac.uk
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Inglis
authors.forename: Kay E
authors.initials: KE
authors.lastname: McNamee
authors.forename: Shi-Lu
authors.initials: SL
authors.lastname: Chia
authors.forename: David
authors.initials: D
authors.lastname: Essex
authors.forename: Marc
authors.initials: M
authors.lastname: Feldmann
authors.forename: Richard O
authors.initials: RO
authors.lastname: Williams
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunt
authors.forename: Tonia
authors.initials: T
authors.lastname: Vincent
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology; D002356:Cartilage / Q000473:pathology; D008297:Male; D051379:Mice; D018847:Opioid Peptides / Q000502:physiology*; D020370:Osteoarthritis, Knee / Q000473:pathology / Q000503:physiopathology*; D010146:Pain / Q000503:physiopathology*; D017450:Receptors, Opioid, mu / Q000502:physiology*
chemical_list: D018847:Opioid Peptides; D017450:Receptors, Opioid, mu