Immunocytochemical Localization of trkA Receptors in Chemically Identified Subgroups of Adult Rat Sensory Neurons

Abstract

Immunocytochemistry has been used to examine the location of trkA, the high-affinity receptor for nerve growth factor, in adult rat dorsal root ganglia, trigeminal ganglia and spinal cord. TrkA immunoreactivity was observed in small and medium sized ganglion cells and in the dorsal horn of the spinal cord. In lumbar L4 and L5 ganglia trkA-immunoreactive cells constitute 40% of dorsal root ganglion cells and range in size from 15 to 45 microns in diameter. Double labelling using markers for various dorsal root ganglion subpopulations revealed that virtually all (92%) trkA-immunoreactive cells express calcitonin gene-related peptide (CGRP) immunoreactivity. In contrast only 4 and 13% of trkA-immunoreactive cells are labelled by the monoclonal antibody LA4 or the lectin Griffonia simplicifolia IB4, markers for small non-peptide-containing cells. Eighteen percent of trkA-immunoreactive cells belong to the 'large light' subpopulation, identified by their strong immunostaining by the neurofilament antibody RT97. TrkA immunoreactivity in the dorsal horn is heaviest in laminae I and II outer, has a similar distribution to CGRP, and is depleted by dorsal rhizotomy. Our results show that trkA-expressing cells in dorsal root ganglia correspond almost exactly with the CGRP, peptide-producing population. The receptor is present not only on cell bodies but also on central terminals. Non-peptide-containing small cells, which constitute 30% of dorsal root ganglion cells, are not trkA-immunoreactive and therefore most probably are functionally independent of nerve growth factor.

Differences in Innervation and Innervated Neurons between Hip and Inguinal Skin

“…Several reports have described the classification of DRG neurons [2,12,17,20]. DRG neurons can be distinguished by immunoreactivity for CGRP and IB4-binding.…”

“…These small neurons may be subclassified into two groups. The first group, comprising peptide-containing neurons, contains CGRP [2,20]. CGRP-expressing neurons terminate in lamina I and the outer layer of lamina II in the spinal dorsal horn [12].…”

“…GDNF has analgesic effects in neuropathic pain states [6], whereas NGF produces thermal and mechanical hyperalgesia [18]. There is a strong correlation between the expression of CGRP and the NGF receptor [2] and between the expression of IB4-binding glycoprotein and the GDNF receptor [12]. Thus, sensitivity to NGF may be higher in DRG neurons innervating the hip than in DRG neurons innervating inguinal skin, whereas sensitivity to GDNF may be higher in DRG neurons innervating inguinal skin than in DRG neurons innervating the hip.…”

“…NGF-sensitive neurons express the highaffinity NGF receptor tyrosine kinase A (TrkA) [2] whereas Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.…”

Muscle injury in rats induces upregulation of inflammatory cytokines in injured muscle and calcitonin gene–related peptide in dorsal root ganglia innervating the injured muscle

“…Increased expression of sensory nerve fibers (substance P, CGRP) in particular was observed after 3 days, along with a significant reduction in CGRP‐positive fibers from 3 to 21 days. CGRP has been identified in small, NGF‐dependent DRG neurons involved in pain perception related to inflammation,19 suggesting that CGRP is a marker of inflammatory pain. Thus, upregulation of CGRP may explain the persistence of muscle injury pain.…”