Spinal interleukin-1beta in a mouse model of arthritis and joint pain.
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.


CONCLUSIONS
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.
Fiorentino
Paolo M
PM
University of Rochester School of Medicine and Dentistry, Rochester, New York 14620, USA.
Tallents
Ross H
RH
Miller
Jen-nie H
JN
Brouxhon
Sabine M
SM
O'Banion
M Kerry
MK
Puzas
J Edward
JE
Kyrkanides
Stephanos
S
D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010003:Osteoarthritis / Q000503:physiopathology*; D010146:Pain / Q000503:physiopathology*; D020671:Posterior Horn Cells / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000502:physiology; D013704:Temporomandibular Joint / Q000503:physiopathology; D015854:Up-Regulation
D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1