title: Cytotoxic targeting of isolectin IB4-binding sensory neurons.
abstract: 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.
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis 55455, USA.
authors.forename: L
authors.initials: L
authors.lastname: Vulchanova
authors.forename: T H
authors.initials: TH
authors.lastname: Olson
authors.forename: L S
authors.initials: LS
authors.lastname: Stone
authors.forename: M S
authors.initials: MS
authors.lastname: Riedl
authors.forename: R
authors.initials: R
authors.lastname: Elde
authors.forename: C N
authors.initials: CN
authors.lastname: Honda
mesh_terms: 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
chemical_list: D000922:Immunotoxins; D037102:Lectins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins