Targeted toxins in pain.

Department of Neurology, Vanderbilt University, Nashville, TN 37212, USA.
Advanced Drug Delivery Reviews (Impact Factor: 12.71). 09/2003; 55(8):1043-54. DOI: 10.1016/S0169-409X(03)00102-9
Source: PubMed

ABSTRACT Although only recently applied to the study of nociception, 'molecular neurosurgery', producing highly selective neural lesions using targeted cytotoxins, has proven a valuable tool for analysis of nociceptive systems and promises to yield much more information on the role of specific types of neurons in pain perception and possibly new pain therapies. Neuropeptide-toxin conjugates, particularly, substance P-saporin, have proven useful research tools and may find clinical applications. Targeting non-lethal moieties (enzymes, genes, viruses) also may prove useful for research and therapeutic purposes.

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    ABSTRACT: It is well known that neurons in the rostral ventromedial medulla (RVM) are involved in descending modulation of nociceptive transmission in the spinal cord. It has been shown that activation of neurokinin-1 receptors (NK-1Rs) in the RVM, which are presumably located on pain facilitating ON cells, produces hyperalgesia whereas blockade of NK-1Rs attenuates hyperalgesia. To obtain a better understanding of the functions of NK-1R expressing neurons in the RVM, we selectively ablated these neurons by injecting the stable analog of substance P (SP), Sar9,Met(O2)11-Substance P, conjugated to the ribosomal toxin saporin (SSP-SAP) into the RVM. Rats received injections of SSP-SAP (1 μM) or an equal volume of 1 μM of saporin conjugated to artificial peptide (Blank-SAP). Stereological analysis of NK-1R- and NeuN-labeled neurons in the RVM was determined 21-24 days after treatment. Withdrawal responses to mechanical and heat stimuli applied to the plantar hindpaw were determined 5-28 days after treatment. Withdrawal responses were also determined before and after intraplantar injection of capsaicin (acute hyperalgesia) or complete Freund’s adjuvant (CFA) (prolonged hyperalgesia).
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