IL-1 beta signaling is required for mechanical allodynia induced by nerve injury and for the ensuing reduction in spinal cord neuronal GRK2.
Many neurotransmitters involved in pain perception transmit signals via G protein-coupled receptors (GPCRs). GPCR kinase 2 (GRK2) regulates agonist-induced desensitization and signaling of multiple GPCRs and interacts with downstream molecules with consequences for signaling. In general, low GRK2 levels are associated with increased responses to agonist stimulation of GPCRs. Recently, we reported that in mice with reduced GRK2 levels, inflammation-induced mechanical allodynia was increased. In addition, mice with impaired interleukin (IL)-1 beta signaling did not develop mechanical allodynia after L5 spinal nerve transection (SNT). We hypothesized that in the L5 SNT model mechanical allodynia would be associated with reduced neuronal GRK2 levels in the spinal cord dorsal horn and that IL-1 beta signaling would be required to induce both the decrease in GRK2 and mechanical allodynia. We show here that in wild type (WT) mice L5 SNT induces a bilateral decrease in neuronal GRK2 expression in the lumbar spinal cord dorsal horn, 1 and 2 weeks after L5 SNT. No changes in GRK2 were observed in the thoracic segments. Moreover, spinal cord GRK2 expression was not decreased in IL-1R(-/-) mice after L5 SNT. These data show that IL-1 beta signaling is not only required for the development of mechanical allodynia, but also to reduce neuronal GRK2 expression. These results suggest a functional relation between the L5 SNT-induced IL-1 beta-mediated decrease in GRK2 and development of mechanical allodynia.
Kleibeuker
Wendy
W
University Medical Centre Utrecht, Laboratory of Psychoneuroimmunology, Lundlaan 6, 3584 EA Utrecht, The Netherlands.
Gabay
Eran
E
Kavelaars
Annemieke
A
Zijlstra
Jitske
J
Wolf
Gilly
G
Ziv
Nadav
N
Yirmiya
Raz
R
Shavit
Yehuda
Y
Tal
Michael
M
Heijnen
Cobi J
CJ
D000818:Animals; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism*; D006930:Hyperalgesia / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D008159:Lumbar Vertebrae; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013127:Spinal Nerves / Q000293:injuries*
D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I; C496568:GRK2 protein, mouse; D054769:G-Protein-Coupled Receptor Kinase 2