Wiley RG, Lappi DA, Vierck CJ (1999) Inhibition of mustard oil-induced thermal hyperalgesia in an operant escape task by substance P-saporin. Neuroscience 1999 Abstracts 271.1. Society for Neuroscience, Miami, FL.
Summary: Substance P (SP) armed with the ribosome inactivating protein, saporin (SAP), selectively destroys neurons expressing the NK-1 receptor, attenuates withdrawal responses after capsaicin injection, after a Chung lesion or CFA and blocks phase 2 of the formalin test. These tests rely on innate “reflex” behaviors (withdrawal or licking) and the primary effects were to mechanical stimuli. In the present study, we sought to determine the effects of lumbar i.t. SP-SAP on reflexes and operant escape responses to thermal stimuli. Rats received lumbar i.t. injections of 175 ng SP-SAP (N=7), 25 ng of [Sar8MetOH11]-SP-SAP (N=8) or PBS with 1 mg/ml BSA (N=8). Nine rats served as naive controls. After recovery from surgery, all rats were adapted to thermal reflex testing and separately trained to escape to a brightly lit room temperature shelf from a dark surface at 47°C, 44°C and 0.3°C. There were no differences between groups at baseline on the escape task or reflex tests at any of the 3 temperatures. When tested at 44°C 3 hours after application of mustard oil to the dorsal surface of both hindpaws, controls spent significantly more time on the escape shelf whereas SP-SAP treated rats did not. In contrast, when tested 3 hrs after mustard oil at 44°C, all rats showed similar reflex responses with decreased latency to licking, more licking and guarding. These results indicate that the SP-SAP lesion of lamina I neurons expressing NK-1 receptor in the spinal dorsal horn prevents enhanced operant escape behavior, but not enhanced reflex responses. That is, the aversive quality of mustard oil-induced thermal hyperalgesia was blocked without interfering with nocifensive reflexes. Also, the anti-hyperalgesia effects ofl umbar intrathecal SP-sap include thermal hyperalgesia. This approach may prove valuable in the treatment of chronic, intractable pain. (This work supported by the NIH and the Department of Veterans Affairs).
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