title: Phenotypic changes in dorsal root ganglion and spinal cord in the collagen antibody-induced arthritis mouse model.
abstract: The mechanisms underlying rheumatoid arthritis (RA)-induced pain are still not fully elucidated, and accumulating data indicate that peripheral inflammation is not the only factor driving pain in these patients. The focus of our work is to investigate the molecular basis for long-term alterations in nociceptive pathways induced by polyarthritis using the collagen antibody-induced arthritis (CAIA) mouse model. In this model, mechanical hypersensitivity outlasts the joint inflammation by weeks. Here we examined expression levels of neuropeptides, ion channels, and nerve injury markers associated with neuropathic and/or inflammatory pain in dorsal root ganglia (DRGs) and spinal cord both during the peak of inflammation (day 15) and when the inflammation has resolved but the hypersensitivity persists (days 45-47). No apparent differences were observed in substance P, calcitonin gene-related peptide, or neuropeptide Y protein expression in DRGs and spinal cord of CAIA mice. However, the neuropeptide galanin, the ATP-gated ion channel P2X3, and calcium channel subunit α2δ1 were significantly increased in the CAIA DRGs as compared to controls, both 15 and 47 days after induction of arthritis. On day 15 there was an increase in expression of two factors associated with nerve injury and cell stress, activating transcription factor 3 and growth-associated protein 43 in DRGs, whereby the latter was still dramatically upregulated after 47 days. In conclusion, this study suggests that long-term joint inflammation has an impact on DRG neurons that resembles both inflammation and nerve injury-induced pain states. Thus, antibody-driven inflammation generates a pain state with a unique neurochemical profile.
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors: Jie
authors: J
authors: Su
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors: Tianle
authors: T
authors: Gao
authors: Department of Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors: Tiejun
authors: T
authors: Shi
authors: Department of Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors: Qiong
authors: Q
authors: Xiang
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors: Xiaojun
authors: X
authors: Xu
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors: Zsuzsanna
authors: Z
authors: Wiesenfeld-Hallin
authors: Department of Neuroscience, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors: Tomas
authors: T
authors: Hökfelt
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors: Camilla I
authors: CI
authors: Svensson
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000633:toxicity*; D001168:Arthritis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D015220:Calcium Channels / Q000378:metabolism; D003094:Collagen / Q000276:immunology*; D004195:Disease Models, Animal; D019004:Galanin / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology*; D006930:Hyperalgesia / Q000209:etiology; D037102:Lectins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013373:Substance P / Q000378:metabolism; D013997:Time Factors
chemical_list: D051700:Activating Transcription Factor 3; D000906:Antibodies; C103002:Atf3 protein, mouse; C512066:CACNA2D1 protein, mouse; D015220:Calcium Channels; D037102:Lectins; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D013373:Substance P; D019004:Galanin; D003094:Collagen
keywords: dorsal root ganglia; ion channels; nerve injury; neuropeptides; pain; rheumatoid arthritis