The 5-HT2A receptor is mainly expressed in nociceptive sensory neurons in rat lumbar dorsal root ganglia

• Published in: Neuroscience Vol. 161; no. 3; pp. 838 - 846
• Main Authors: Van Steenwinckel, J, Noghero, A, Thibault, K, Brisorgueil, M.-J, Fischer, J, Conrath, M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 07.07.2009; Elsevier
• Subjects: 5-HT; Animals; Biological and medical sciences; Cell Membrane - metabolism; Cell Size; Cytoplasm - metabolism; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Ganglia, Spinal - metabolism; Ganglia, Spinal - ultrastructure; HPLC; Hydroxyindoleacetic Acid - metabolism; immunocytochemistry; Lectins - metabolism; Lumbar Vertebrae; Neurofilament Proteins - metabolism; Neurology; Nociceptors - cytology; Nociceptors - metabolism; Nociceptors - ultrastructure; Parvalbumins - metabolism; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2A - metabolism; satellite cell; Satellite Cells, Perineuronal - physiology; Satellite Cells, Perineuronal - ultrastructure; sensory cell; Serotonin - metabolism; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Substance P - metabolism; TRPV Cation Channels - metabolism; ultrastructure; Vertebrates: nervous system and sense organs; TX; phosphate buffer; sensory cell; phosphate-buffered saline; PARV; BSA; transient receptor potential vanilloid type 1 receptor; high liquid performance chromatography; substance P; SP; HPLC; ISH; Triton X-100; PBS; immunocytochemistry; calcitonin gene-related peptide; TRPV1; ultrastructure; 5-HT2AR; PB; 5-hydroxyindoleacetic acid; satellite cell; 5-HIAA; parvalbumin; dorsal root ganglion; DRG; 5-HT receptor subtype 2 A; 5-HT; CGRP; bovine serum albumin; in situ hybridization; Nociception; 5-HT2A serotonin receptor; Spinal cord; Rat; Serotonin; Immunocytochemistry; Rodentia; Central nervous system; HPLC chromatography; Vertebrata; Mammalia; Ultrastructure; Animal; Neurotransmitter; Sensory neuron; Spinal ganglion; Satellite cell
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.03.087

Abstract 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 Aδ or Aβ 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 Aδ or Aβ fibers, and in the control of cellular excitability of some dorsal root cell bodies through a paracrine mechanism of action.