Cytotoxic targeting of isolectin IB4-binding sensory neurons.
The isolectin I-B4 (IB4) binds specifically to a subset of small sensory neurons. We used a conjugate of IB4 and the toxin saporin to examine in vivo the contribution of IB4-binding sensory neurons to nociception. A single dose of the conjugate was injected unilaterally into the sciatic nerve of rats. The treatment resulted in a permanent selective loss of IB4-binding neurons as indicated by histological analysis of dorsal root ganglia, spinal cord, and skin from treated animals. Behavioral measurements showed that 7-10 days after the injection, conjugate-treated rats had elevated thermal and mechanical nociceptive thresholds. However, 21 days post-treatment the nociceptive thresholds returned to baseline levels. These results demonstrate the utility of the IB4-saporin conjugate as a tool for selective cytotoxic targeting and provide behavioral evidence for the role of IB4-binding neurons in nociception. The decreased sensitivity to noxious stimuli associated with the loss of IB4-binding neurons indicates that these sensory neurons are essential for the signaling of acute pain. Furthermore, the unexpected recovery of nociceptive thresholds suggests that the loss of IB4-binding neurons triggers changes in the processing of nociceptive information, which may represent a compensatory mechanism for the decreased sensitivity to acute pain.
Vulchanova
L
L
Department of Neuroscience, University of Minnesota, Minneapolis 55455, USA.
Olson
T H
TH
Stone
L S
LS
Riedl
M S
MS
Elde
R
R
Honda
C N
CN
D000818:Animals; D002452:Cell Count; D000922:Immunotoxins / Q000494:pharmacology; D037102:Lectins / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009186:Myelin Sheath / Q000187:drug effects; D009699:N-Glycosyl Hydrolases; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D009619:Nociceptors / Q000502:physiology*; D017288:Pain Threshold / Q000187:drug effects; D010940:Plant Proteins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000922:Immunotoxins; D037102:Lectins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins