Wiley RG, Miller SA, Kline IV RH (2003) Selective destruction of MOR expressing dorsal horn neurons using intrathecal dermorphin-saporin. Neuroscience 2003 Abstracts 174.15. Society for Neuroscience, New Orleans, LA.
Summary: Evidence suggests that the mu opiate receptor (MOR) is key to the analgesic action of morphine. In the present study, we sought to determine if a disulfide conjugate of the mu opioid peptide, dermorphin, to the ribosome-inactivating protein, saporin, (derm-sap) would destroy neurons expressing MOR in the substantia gelatinosa (SG) of the spinal cord. Derm-sap was injected into the lumbar subarachnoid space of anesthetized adult, male Sprague-Dawley rats using a catheter inserted through the atlanto-occipital membrane and passed 8 cm caudally. The catheter was removed 15 minutes after toxin injection. Rats were sacrificed after 2 weeks, and 40 um transverse frozen sections of the L4 spinal segment were processed for immunohistochemical demonstration of MOR, NeuN, calbindin D28k, parvalbumin, NK-1R and for Nissl staining. In control rats, beta-funaltrexamine was injected just before derm-sap or derm-sap was pre-treated to reduce the disulfide bond which dissociates the toxin and neuropeptide. MOR staining in the SG was evaluated using quantitative densitometry. Initial experiments revealed a dose-related decrease in MOR staining in the dorsal horn without effect on dorsal root ganglia at doses up to 1000 ng. The maximally tolerated dose of derm-sap (500 ng) selectively decreased MOR staining by 54% as did multilevel lumbar dorsal rhizotomy. Combining 500 ng of derm-sap and multilevel rhizotomy produced 92% loss of MOR staining in the SG. Based on analysis of non-co-localized markers and control experiments, we interpret the results to indicate that intrathecal derm-sap selectively destroys MOR-expressing neurons in the SG without toxicity to primary afferents. This lesion will be useful in analysis of opioid mechanisms in the dorsal horn.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)