OR WAIT null SECS
(ACR2014) Top picks from RheumatologyNetwork Editorial Board members. Nancy Lane MD liked a mouse study that inquires why so many arthritis patients continue to experience pain despite rheumatology's success at conquering inflammation.
Woller SA, Ochletree C, YakshTL, CorrM. Mechanical Allodynia in Arthritic Mice is Regulated by Innate and Adaptive Immunity at the Spinal Level. ACR Abstract #2784. 2014 66:S1306. Abstract Supplement, 2014 ACR/ARHP Annual Meeting
Individuals with arthritis frequently develop persistent pain, despite adequate treatment of synovitis. Recently, it has been shown that Toll-like receptor 4 (TLR4) mediates the transition from acute to chronic pain despite resolution of swelling in an animal model of arthritis.1 Animals deficient in TLR4 showed an attenuation of the late, but not the early, phase of pain.
This receptor is unique in signaling through both MyD88-dependent and -independent pathways. MyD88 (myeloid differentiation primary response gene 88) and TRIF, a mediator in response to Toll-like receptors, play distinct roles in the development of pain. Mice lacking MyD88 do not develop swelling or allodynia, while those deficient in TRIF develop prolonged pain outlasting the period of inflammation.
In order to further understand the role of TLR signaling, these investigators examined the development of arthritis and persistent pain in mice deficient in the adaptor proteins involved in these pathways. They found that wild-type (WT) mice developed a persistent increase in mechanical reactivity that outlasts the period of inflammation. Tlr4-/-mice, lacking Toll-like receptor 4, develop an initial increase in reactivity, which resolves concurrent with inflammation.
Genes in the spinal cord tissue from of WT and TLR4 mice harvested on Day 10 of arthritis showed differences in expression levels of interleukin 2 (IL2), Receptor activator of nuclear factor kappa-B ligand (RANKL), interferfon (IFN) Î², and tumor necrosis factor (TNF) transcripts. Mice deficient in TNF showed significantly less arthritic pain (p<0.001). In those lacking RANKL, pain resolved with resolution of inflammation (p<0.05), similar to the response in mice devicient in TLR4. Mice lacking genes for IFNÎ² developed pain that was not noticeably different than that in the WT mice.
These results suggest that pain can persist after other signs of inflammation. The innate and adaptive immune systems have distinct roles in chronic pain development, and this pain cannot be attributed solely to increased TNF or IFNÎ².
1. Christianson CA, Dumlao DS, Stokes JA et al.Spinal TLR4 mediates the transition to a persistent mechanical hypersensitivity after the resolution of inflammation in serum-transferred arthritis.Pain. 2011; 152(12): 2881–2891. doi: 10.1016/j.pain.2011.09.020