Spinal interleukin-1[beta] 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-1[beta] (IL-1[beta]) in central processing of pain is important in the development of arthritis.Methods: Col1-IL-1[beta][XAT] mice and GFAP-IL-1[beta][XAT] 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-1[beta] 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-1[beta][XAT] mice. The effects of IL-1RI receptor inhibition in GFAP-IL-1[beta][XAT] mice were studied in the GFAP-IL-1[beta][XAT]-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-1[beta][XAT] mouse model resulted in up-regulation of murine IL-1[beta] at the dorsal horns. Moreover, intrathecal inhibition of IL-1RI in Col1-IL-1[beta][XAT] mice with arthritis led to amelioration of joint pathology and attenuation of the attendant joint pain. Overexpression of spinal IL-1[beta] in the recently developed GFAP-IL-1[beta][XAT] 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-1[beta], and suggest the presence of a bidirectional central nervous system-peripheral joints crosstalk that may contribute to the development, expansion, and exacerbation of arthritis. [ABSTRACT FROM AUTHOR]