title: Collagen antibody-induced arthritis evokes persistent pain with spinal glial involvement and transient prostaglandin dependency.
abstract: OBJECTIVE
  Pain is one of the most debilitating symptoms reported by rheumatoid arthritis (RA) patients. While the collagen antibody-induced arthritis (CAIA) model is used for studying the effector phase of RA pathologic progression, it has not been evaluated as a model for studies of pain. Thus, this study was undertaken to examine pain-like behavior induced by anticollagen antibodies and to assess the effect of currently prescribed analgesics for RA. In addition, the involvement of spinal glia in antibody-induced pain was explored.
  
  
  METHODS
  CAIA was induced in mice by intravenous injection of a collagen antibody cocktail, followed by intraperitoneal injection of lipopolysaccharide. Disease severity was assessed by visual and histologic examination. Pain-like behavior and the antinociceptive effect of diclofenac, buprenorphine, gabapentin, pentoxifylline, and JNK-interacting protein 1 were examined in mechanical stimulation experiments. Spinal astrocyte and microglia reactivity were investigated by real-time polymerase chain reaction and immunohistochemistry.
  
  
  RESULTS
  Following the induction of CAIA, mice developed transient joint inflammation. In contrast, pain-like behavior was observed prior to, and outlasted, the visual signs of arthritis. Whereas gabapentin and buprenorphine attenuated mechanical hypersensitivity during both the inflammatory and postinflammatory phases of arthritis, diclofenac was antinociceptive only during the inflammatory phase. Spinal astrocytes and microglia displayed time-dependent signs of activation, and inhibition of glial activity reversed CAIA-induced mechanical hypersensitivity.
  
  
  CONCLUSIONS
  CAIA represents a multifaceted model for studies exploring the mechanisms of pain induced by inflammation in the articular joint. Our findings of a time-dependent prostaglandin and spinal glial contribution to antibody-induced pain highlight the importance of using appropriate disease models to assess joint-related pain.
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Duygu B
authors.initials: DB
authors.lastname: Bas
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.forename: Katalin
authors.initials: K
authors.lastname: Sandor
authors.forename: Nilesh M
authors.initials: NM
authors.lastname: Agalave
authors.forename: Johanna
authors.initials: J
authors.lastname: Lundberg
authors.forename: Simone
authors.initials: S
authors.lastname: Codeluppi
authors.forename: Azar
authors.initials: A
authors.lastname: Baharpoor
authors.forename: Kutty S
authors.initials: KS
authors.lastname: Nandakumar
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Camilla I
authors.initials: CI
authors.lastname: Svensson
mesh_terms: D000588:Amines / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D018771:Arthralgia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D001169:Arthritis, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D002047:Buprenorphine / Q000627:therapeutic use; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D004008:Diclofenac / Q000627:therapeutic use; D004195:Disease Models, Animal; D000077206:Gabapentin; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D011453:Prostaglandins / Q000378:metabolism*; D013131:Spine / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D011453:Prostaglandins; D004008:Diclofenac; D002047:Buprenorphine; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin