title: Characterization of the acute and persistent pain state present in K/BxN serum transfer arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic autoimmune arthritis that affects approximately 1% of the population. Synovial inflammation cannot fully explain the level of pain reported by patients and facilitation of pain processing at the spinal level has been implicated. We characterized the K/BxN serum transfer arthritis model as a model of joint inflammation-induced pain and examined pharmacologic responsiveness and spinal glia activation. Mechanical allodynia developed congruently with joint swelling. Surprisingly, allodynia persisted after resolution of inflammation. At the peak of joint inflammation (days 4-10), hypersensitivity was attenuated with i.p. etanercept, gabapentin, and ketorolac. Following resolution of synovial inflammation (days 19-23), only gabapentin relieved allodynia. The superficial dorsal horn of arthritic mice displayed increased staining of microglia at early and late time points, but astrocyte staining increased only during the inflammatory phase. ATF3, a marker of nerve injury, was significantly increased in the lumbar dorsal root ganglia during the late phase (day 28). Hence, serum transfer in the K/BxN serum transfer arthritis model produces a persistent pain state, where the allodynia during the inflammatory state is attenuated by TNF and prostaglandin inhibitors, and the pharmacology and histochemistry data suggest a transition from an inflammatory state to a state that resembles a neuropathic condition over time. Therefore, the K/BxN serum transfer model represents a multifaceted model for studies exploring pain mechanisms in conditions of joint inflammation and may serve as a platform for exploring novel treatment strategies for pain in human arthritic conditions.
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA Department of Anesthesiology, University of California, San Diego, La Jolla, CA, USA Division of Rheumatology, Allergy and Immunology, University of California, San Diego, La Jolla, CA, USA Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Christianson
authors.forename: Maripat
authors.initials: M
authors.lastname: Corr
authors.forename: Gary S
authors.initials: GS
authors.lastname: Firestein
authors.forename: Anahita
authors.initials: A
authors.lastname: Mobargha
authors.forename: Tony L
authors.initials: TL
authors.lastname: Yaksh
authors.forename: Camilla I
authors.initials: CI
authors.lastname: Svensson
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000588:Amines / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001323:Autoantibodies / Q000009:adverse effects; D001522:Behavior, Animal / Q000502:physiology; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D004195:Disease Models, Animal; D000077206:Gabapentin; D005727:Ganglia, Spinal / Q000378:metabolism; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology; D007719:Knee Joint / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D010146:Pain / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D010812:Physical Stimulation / Q000009:adverse effects; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D044967:Serum; D013116:Spinal Cord / Q000473:pathology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
chemical_list: D051700:Activating Transcription Factor 3; D000588:Amines; D000700:Analgesics; C103002:Atf3 protein, mouse; D001323:Autoantibodies; D003509:Cyclohexanecarboxylic Acids; D011948:Receptors, Antigen, T-Cell; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D005956:Glucose-6-Phosphate Isomerase