title: Intrathecal substance p-saporin attenuates operant escape from nociceptive thermal stimuli.
abstract: Destruction of neurons in the superficial dorsal horn that express substance P receptor (NK-1R) has been reported to block development of behavioral hypersensitivity following peripheral sensitization of nociceptors. Baseline sensitivity was not altered in these rat models that assessed innate reflex responses (i.e. hind-paw withdrawal to thermal or mechanical stimulation). In the present study, we evaluated effects of intrathecal substance P-saporin (SP-sap), a toxin selective for cells expressing NK-1R, on operant escape responses of rats to thermal stimulation. For comparison, lick/guard reflex testing was performed. Injection of a modest dose (175 ng) of SP-sap into the lumbar subarachnoid space produced a partial loss of lamina I/II NK-1R-expressing dorsal horn neurons but did not affect NK-1R-expressing neurons in deeper laminae. Lick/guard responses to 0.3, 44 or 47 degrees C were not affected after SP-sap treatment, but escape responses to these temperatures were significantly attenuated. Three hours after application of mustard oil to the dorsal surface of both hind paws, escape from 44 degrees C was enhanced for controls but not SP-sap-treated rats. Lick/guard responses were enhanced by mustard oil for both SP-sap and control animals. Administration of morphine (1.0 mg/kg, s.c.) before testing decreased escape responding at 47 degrees C for both controls and SP-sap rats. Thus, partial loss of NK-1R-expressing neurons in the superficial dorsal horn attenuated thermal nociceptive sensitivity and prevented secondary hyperalgesia when studied with an operant algesia assay, in contrast to innate reflexes which were less sensitive to modification by intrathecal SP-sap.
authors.affiliation: Department of Neuroscience and McKnight Brain Institute, University of Florida College of Medicine, P.O. Box 100244, Gainesville, FL 32610, USA. vierck@mbi.ufl.edu
authors.forename: C J
authors.initials: CJ
authors.lastname: Vierck
authors.forename: R H
authors.initials: RH
authors.lastname: Kline
authors.forename: R G
authors.initials: RG
authors.lastname: Wiley
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal; D002211:Capsaicin / Q000009:adverse effects; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects*; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia; D000922:Immunotoxins / Q000633:toxicity*; D007278:Injections, Spinal / Q000379:methods; D009020:Morphine / Q000008:administration & dosage; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013116:Spinal Cord / Q000033:anatomy & histology / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives / Q000633:toxicity*
chemical_list: D000701:Analgesics, Opioid; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; C468274:substance P-saporin; D013373:Substance P; D009020:Morphine; D000076985:Saporins; D002211:Capsaicin