title: Genetic evidence for involvement of neuronally expressed S1P₁ receptor in nociceptor sensitization and inflammatory pain.
abstract: Sphingosine-1-phosphate (S1P) is a key regulator of immune response. Immune cells, epithelia and blood cells generate high levels of S1P in inflamed tissue. However, it is not known if S1P acts on the endings of nociceptive neurons, thereby contributing to the generation of inflammatory pain. We found that the S1P₁ receptor for S1P is expressed in subpopulations of sensory neurons including nociceptors. Both S1P and agonists at the S1P₁ receptor induced hypersensitivity to noxious thermal stimulation in vitro and in vivo. S1P-induced hypersensitivity was strongly attenuated in mice lacking TRPV1 channels. S1P and inflammation-induced hypersensitivity was significantly reduced in mice with a conditional nociceptor-specific deletion of the S1P₁ receptor. Our data show that neuronally expressed S1P₁ receptors play a significant role in regulating nociceptor function and that S1P/S1P₁ signaling may be a key player in the onset of thermal hypersensitivity and hyperalgesia associated with inflammation.
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University, Innsbruck, Austria. norbert.mair@i-med.ac.at
authors.forename: Norbert
authors.initials: N
authors.lastname: Mair
authors.forename: Camilla
authors.initials: C
authors.lastname: Benetti
authors.forename: Manfred
authors.initials: M
authors.lastname: Andratsch
authors.forename: Michael G
authors.initials: MG
authors.lastname: Leitner
authors.forename: Cristina E
authors.initials: CE
authors.lastname: Constantin
authors.forename: Maria
authors.initials: M
authors.lastname: Camprubí-Robles
authors.forename: Serena
authors.initials: S
authors.lastname: Quarta
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Biasio
authors.forename: Rohini
authors.initials: R
authors.lastname: Kuner
authors.forename: Ian L
authors.initials: IL
authors.lastname: Gibbins
authors.forename: Michaela
authors.initials: M
authors.lastname: Kress
authors.forename: Rainer V
authors.initials: RV
authors.lastname: Haberberger
mesh_terms: D000818:Animals; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009619:Nociceptors / Q000378:metabolism / Q000502:physiology; D010146:Pain / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D049349:Receptors, Lysosphingolipid / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D012867:Skin / Q000294:innervation / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine