The role of proinflammatory cytokines in the generation and maintenance of joint pain.
The proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) not only promote and maintain inflammation, they also contribute to the generation and maintenance of inflammatory pain by acting at nociceptive nerve cells. A large proportion of dorsal root ganglion (DRG) neurons express TNF receptors and receptor units for stimulation with IL-6. In the rat model of antigen-induced arthritis (AIA), neutralization of TNF-alpha by etanercept and infliximab reduced inflammation-evoked mechanical hyperalgesia at the inflamed knee joint. This treatment also attenuated the infiltration of macrophages into the DRGs usually observed during the acute phase of AIA. Intra-articular application of etanercept reduced the responses of C-fibers to mechanical stimulation of the inflamed joint but did not influence responses to stimulation of the normal joint. Finally, in cultured DRG neurons TNF-alpha increased the proportion of neurons that express the TRPV1 receptor and may thus contribute to the generation of inflammation-evoked thermal hyperalgesia.
Schaible
H-G
HG
Institute of Physiology/Neurophysiology, Universitätsklinikum Jena, Jena, Germany. Hans-Georg.Schaible@mti.uni-jena.de
von Banchet
G Segond
GS
Boettger
M K
MK
Bräuer
R
R
Gajda
M
M
Richter
F
F
Hensellek
S
S
Brenn
D
D
Natura
G
G
D000818:Animals; D018771:Arthralgia / Q000473:pathology*; D001168:Arthritis / Q000473:pathology; D001169:Arthritis, Experimental / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000473:pathology; D006930:Hyperalgesia / Q000473:pathology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007719:Knee Joint / Q000473:pathology; D009475:Neurons, Afferent / Q000473:pathology; D051381:Rats; D050916:TRPV Cation Channels / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D014409:Tumor Necrosis Factor-alpha