Impaired acute and inflammatory nociception in mice lacking the p50 subunit of NF-kappaB.
The transcription factor NF-kappaB is thought to play an essential role in inflammatory processes and pain. However, the in vivo function of individual NF-kappaB subunits in the development and processing of nociceptive responses is not clarified. In this study we investigated the role of the p50 subunit of NF-kappaB in models of acute and persistent nociception using NF-kappaB p50(-/-) mice. We found that these mice showed impaired basal responses to mechanical as well as thermal noxious stimulation in the dynamic plantar as well as the hot plate test, respectively, in comparison with wild-type mice. In the formalin test we observed a decreased nociceptive behavior in the first and the second phase in NF-kappaB p50(-/-) mice. In a model of persistent inflammatory hyperalgesia these mice also showed a reduced hyperalgesia to a thermal stimulus, which was in accordance with a lower cyclooxygenase-2 expression in the spinal cord after peripheral inflammatory stimulation. Taken together, our data indicate that the p50 subunit of NF-kappaB is of importance in acute and persistent inflammatory pain. The participation to persistent pain might rely on activation of NF-kappaB by inflammatory stimuli while the contribution to acute pain responses might be related to constitutive NF-kappaB activity in neurons of the nociceptive system.
Niederberger
Ellen
E
Pharmazentrum Frankfurt/ZAFES, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. e.niederberger@em.uni-frankfurt.de
Schmidtko
Achim
A
Gao
Wei
W
Kühlein
Hilmar
H
Ehnert
Corina
C
Geisslinger
Gerd
G
D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D005557:Formaldehyde; D006358:Hot Temperature; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000235:genetics* / Q000502:physiology*; D010146:Pain / Q000209:etiology* / Q000235:genetics*; D010147:Pain Measurement; D010812:Physical Stimulation; D011930:Reaction Time; D013268:Stimulation, Chemical; D015054:Zymosan
D052002:NF-kappa B p50 Subunit; D005557:Formaldehyde; D015054:Zymosan; D051546:Cyclooxygenase 2