Developmental shift of vanilloid receptor 1 (VR1) terminals into deeper regions of the superficial dorsal horn: correlation with a shift from TrkA toRet expression by dorsal root ganglion neurons
A. Guo et al., Developmental shift of vanilloid receptor 1 (VR1) terminals into deeper regions of the superficial dorsal horn: correlation with a shift from TrkA toRet expression by dorsal root ganglion neurons, EUR J NEURO, 14(2), 2001, pp. 293-304
The cloned vanilloid receptor VR1 can be activated by capsaicin and by ther
mal stimuli. The pattern of nerve terminals that contain VR1 in adult rat s
pinal cord does not correspond to axons that arise from a single subset of
dorsal root ganglion neurons. Thus, we postulated that the basis underlying
this complexity might be better understood from a developmental perspectiv
e. First, using capsaicin-induced hyperalgesia as a measure of VR1 function
, we found that vanilloid receptors were functional as early as postnatal d
ay 10 (P10), although hyperalgesia was of longer duration in adult. Interes
tingly, the appearance of VR1 protein in terminals of dorsal root ganglion
neurons shifts over this postnatal period. From embryonic day 16 to P20, th
e majority of VR1 protein in the spinal cord was observed in lamina I. As a
nimals matured, VR1 protein became more abundant in lamina II, particularly
in the inner portion. Consistent with these observations, the number of do
rsal root ganglion neurons coexpressing VR1 and isolectin B4 binding sites
doubled while the number of neurons that had both VR1 and substance P remai
ned relatively constant from P2 to P10. In peripheral processes, the number
of VR1-positive nerve fibres and terminals in cutaneous structures in post
natal day 10 was half of that in adults. We also show that the association
of VR1 with Ret is the reciprocal of the association of VR1 with Trk A. The
se results suggest that neurotrophins may regulate the extent to which popu
lations of dorsal root ganglion neurons express VR1.