OBJECTIVE: Pain from arthritis has been associated with peripheral sensitization of primary sensory afferents and the development of inflammation at the dorsal horns. This study was undertaken to determine whether the role of spinal interleukin-1beta (IL-1beta) in central processing of pain is important in the development of arthritis. METHODS: Col1-IL-1betaXAT mice and GFAP-IL-1betaXAT mice were injected with the feline immunodeficiency virus (FIV) (Cre) vector in the right and left temporomandibular joints (TMJs), or in the cisterna magna, respectively, to induce IL-1beta expression in the dorsal horns of the spinal horn. To inhibit intrathecal IL-1 receptor type I (IL-1RI) signaling, FIV(IL-1Ra) vector was injected into the cisterna magna of Col1-IL-1betaXAT mice. The effects of IL-1RI receptor inhibition in GFAP-IL-1betaXAT mice were studied in the GFAP-IL-1betaXAT-IL-1RI(-/-) compound mouse model. Neuroinflammatory, sensory, and behavioral changes were evaluated in conjunction with arthritic changes in the TMJ, assessed by histopathologic and immunohistochemical analyses. RESULTS: Induction of an osteoarthritis-like condition in the TMJ in the Col1-IL-1betaXAT mouse model resulted in up-regulation of murine IL-1beta at the dorsal horns. Moreover, intrathecal inhibition of IL-1RI in Col1-IL-1betaXAT mice with arthritis led to amelioration of joint pathology and attenuation of the attendant joint pain. Overexpression of spinal IL-1beta in the recently developed GFAP-IL-1betaXAT somatic mosaic model of neuroinflammation led to development of arthritis-like pathology accompanied by increased pain-like behavior. CONCLUSION: Our results indicate that joint pathology and pain are dependent on spinal IL-1beta, and suggest the presence of a bidirectional central nervous system-peripheral joints crosstalk that may contribute to the development, expansion, and exacerbation of arthritis.
OBJECTIVE:Pain from arthritis has been associated with peripheral sensitization of primary sensory afferents and the development of inflammation at the dorsal horns. This study was undertaken to determine whether the role of spinal interleukin-1beta (IL-1beta) in central processing of pain is important in the development of arthritis. METHODS: Col1-IL-1betaXAT mice and GFAP-IL-1betaXAT mice were injected with the feline immunodeficiency virus (FIV) (Cre) vector in the right and left temporomandibular joints (TMJs), or in the cisterna magna, respectively, to induce IL-1beta expression in the dorsal horns of the spinal horn. To inhibit intrathecal IL-1 receptor type I (IL-1RI) signaling, FIV(IL-1Ra) vector was injected into the cisterna magna of Col1-IL-1betaXAT mice. The effects of IL-1RI receptor inhibition in GFAP-IL-1betaXAT mice were studied in the GFAP-IL-1betaXAT-IL-1RI(-/-) compound mouse model. Neuroinflammatory, sensory, and behavioral changes were evaluated in conjunction with arthritic changes in the TMJ, assessed by histopathologic and immunohistochemical analyses. RESULTS: Induction of an osteoarthritis-like condition in the TMJ in the Col1-IL-1betaXAT mouse model resulted in up-regulation of murineIL-1beta at the dorsal horns. Moreover, intrathecal inhibition of IL-1RI in Col1-IL-1betaXAT mice with arthritis led to amelioration of joint pathology and attenuation of the attendant joint pain. Overexpression of spinal IL-1beta in the recently developed GFAP-IL-1betaXAT somatic mosaic model of neuroinflammation led to development of arthritis-like pathology accompanied by increased pain-like behavior. CONCLUSION: Our results indicate that joint pathology and pain are dependent on spinal IL-1beta, and suggest the presence of a bidirectional central nervous system-peripheral joints crosstalk that may contribute to the development, expansion, and exacerbation of arthritis.
Authors: Jon Lampa; Marie Westman; Diana Kadetoff; Anna Nordenstedt Agréus; Erwan Le Maître; Caroline Gillis-Haegerstrand; Magnus Andersson; Mohsen Khademi; Maripat Corr; Christina A Christianson; Ada Delaney; Tony L Yaksh; Eva Kosek; Camilla I Svensson Journal: Proc Natl Acad Sci U S A Date: 2012-07-16 Impact factor: 11.205
Authors: W H Lim; J Toothman; J H Miller; R H Tallents; S M Brouxhon; M E Olschowka; S Kyrkanides Journal: J Dent Res Date: 2009-06 Impact factor: 6.116
Authors: Stephanos Kyrkanides; Ross H Tallents; Jen-Nie H Miller; Mallory E Olschowka; Renee Johnson; Meixiang Yang; John A Olschowka; Sabine M Brouxhon; M Kerry O'Banion Journal: J Neuroinflammation Date: 2011-09-07 Impact factor: 8.322