The 5-HT2A receptor is mainly expressed in nociceptive sensory neurons in rat lumbar dorsal root ganglia.
Several lines of evidence indicate that peripheral 5-HT2A receptors are involved in the development of inflammatory and neuropathic pain. However, their localization in sensory cell bodies is not accurately known. We therefore studied 5-HT2A receptor distribution in rat lumbar dorsal root ganglia using immunocytochemistry. Forty percent of L3 lumbar dorsal root ganglion cells were immunoreactive for 5-HT2A receptor. Most were small- to medium-sized cell bodies. Double-labeled experiments revealed that they expressed various chemical phenotypes. The smaller 5-HT2AR cell bodies often bind the isolectin B4 although some 5-HT2AR cell bodies also express substance P (SP). Many 5-HT2A-positive small dorsal root ganglion cells expressed the capsaicin receptor transient receptor potential vanilloid type 1 receptor (TRPV1), confirming their nociceptive nature. In addition, a few large cell bodies were labeled for 5-HT2A, and they also expressed NF200 suggesting that they were at the origin of Adelta or Abeta fibers. A total absence of double labeling with parvalbumin showed that they were not proprioceptors. 5-HT2A immunoreactivity in dorsal root ganglia cells was found in the cytoplasm and along the plasma membrane at the interface between sensory cell and the adjacent satellite cells; this distribution was confirmed under the electron microscope, and suggested a functional role for the 5-HT2A receptor at these sites. We therefore investigated the presence of 5-HT and 5-HIAA in lumbar dorsal root ganglia by high performance liquid chromatography. There were 5.75+/-0.80 ng 5-HT and 3.19+/-0.37 ng 5-hydroxyindoleacetic acid (5-HIAA) per mg of protein with a ratio 5-HIAA/5-HT of 0.67+/-0.10, similar to values typically observed in brain tissues. These findings suggest that 5-HT, via the 5-HT2AR, may be involved in the peripheral control of sensory afferents, mainly unmyelinated nociceptors and to a lesser extent neurons with Adelta or Abeta fibers, and in the control of cellular excitability of some dorsal root cell bodies through a paracrine mechanism of action.
Van Steenwinckel
J
J
Neurobiologie des Signaux Intercellulaires, CNRS UMR 7101, Université Pierre et Marie Curie, Paris, France.
Noghero
A
A
Thibault
K
K
Brisorgueil
M-J
MJ
Fischer
J
J
Conrath
M
M
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D048429:Cell Size; D003593:Cytoplasm / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008159:Lumbar Vertebrae; D016900:Neurofilament Proteins / Q000378:metabolism; D009619:Nociceptors / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D010320:Parvalbumins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D027161:Satellite Cells, Perineuronal / Q000502:physiology / Q000648:ultrastructure; D012701:Serotonin / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism
D037102:Lectins; D016900:Neurofilament Proteins; D010320:Parvalbumins; D044402:Receptor, Serotonin, 5-HT2A; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C051774:neurofilament protein H; D012701:Serotonin; D013373:Substance P; D006897:Hydroxyindoleacetic Acid