Distribution of P2X(3)-immunoreactive fibers in hairy and glabrous skin of the rat

J Comp Neurol. 2009 Jun 20;514(6):555-66. doi: 10.1002/cne.22048.


The skin is innervated by two populations of unmyelinated sensory fibers, the peptidergic and nonpeptidergic, which transmit nociceptive information to the central nervous system. The peptidergic population expresses neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) and has both cutaneous and visceral targets. The nonpeptidergic population expresses the purinergic receptor P2X(3), binds the isolectin B4 (IB4), and innervates mainly the epidermis. To date, the peptidergic nociceptor population in cutaneous tissue of the rat has been well characterized, whereas the nonpeptidergic innervation pattern has lacked an adequate description. To this aim, we used light microscopic immunocytochemistry to investigate the pattern of P2X(3)-immunoreactive (-IR) fiber innervation of both hairy and glabrous skin from male Sprague-Dawley rats. Our results show extensive P2X(3)-IR fibers throughout the upper and lower dermis. Thick bundles of P2X(3)-IR fibers were found to run in parallel with the dermal-epidermal junction and projected multiple thin collateral axons that penetrated the epidermal layer, creating a dense network of innervation throughout the entire epidermis. The distribution of P2X(3)-IR fibers in the epidermis was far more extensive than the distribution of CGRP-IR fibers. P2X(3)-IR fibers also innervate hair follicles but were rarely found in close proximity to glands and blood vessels. The present results suggest a primary role for P2X(3)-IR fibers in the detection of noxious stimuli in cutaneous tissue and provide an anatomical basis for future studies examining a possible functionally distinct role of nonpeptidergic nociceptors in the transmission of nociceptive signals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / analysis
  • Dermis / innervation
  • Epidermis / innervation
  • Hair Follicle / innervation
  • Hindlimb / anatomy & histology
  • Hindlimb / innervation
  • Immunohistochemistry
  • Male
  • Nerve Fibers / chemistry*
  • Neurofilament Proteins / analysis
  • Photomicrography
  • Rats / anatomy & histology*
  • Rats / physiology*
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2 / analysis*
  • Receptors, Purinergic P2X3
  • Sensory Receptor Cells / chemistry*
  • Sensory Receptor Cells / cytology*
  • Skin / blood supply
  • Skin / innervation*
  • Ubiquitin Thiolesterase / analysis


  • Neurofilament Proteins
  • P2rx3 protein, rat
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X3
  • neurofilament protein H
  • UCHL1 protein, rat
  • Ubiquitin Thiolesterase
  • Calcitonin Gene-Related Peptide