Targeted toxins in pain
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.
- SourceAvailable from: Robert Hamilton Kline, IV
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- "The density of dorsal horn MOR1 (Fig. 1 B) staining was significantly reduced by ϳ34% ( p ϭ 0.01; F ϭ 7.2; df ϭ 1; one-way ANOVA) after lumbar intrathecal Derm-sap [500 ng, intrathecal (i.t.)]. Loss of dorsal horn MOR1 was predominately medial in lamina II (Fig. 1 B), in agreement with our previous reports (Wiley and Lappi, 2003). Specific staining for the C-terminus splice variant of the -opioid receptor MOR1C appeared as thin-beaded processes in laminas I and II (Abbadie et al., 2001) (Fig. 1 D). "
ABSTRACT: The role of spinal cord mu-opioid receptor (MOR)-expressing dorsal horn neurons in nociception and morphine analgesia is incompletely understood. Using intrathecal dermorphin-saporin (Derm-sap) to selectively destroy MOR-expressing dorsal horn neurons, we sought to determine the role of these neurons in (1) normal baseline reflex nocifensive responses to noxious thermal stimulation (hotplate, tail flick) and to persistent noxious chemical stimulation (formalin) and (2) the antinociceptive activity of intrathecal and systemic morphine in the same tests. Lumbar intrathecal Derm-sap (500 ng) produced (1) partial loss of lamina II MOR-expressing dorsal horn neurons, (2) no effect on MOR-expressing dorsal root ganglion neurons, and (3) no change in baseline tail-flick and hotplate reflex nocifensive responses. Derm-sap treatment attenuated the antinociceptive action of both intrathecal and systemic morphine on hotplate responses. Derm-sap treatment had two effects in the formalin test: (1) increased baseline nocifensive responding and (2) reduced antinociceptive action of systemic morphine. We conclude that MOR-expressing dorsal horn neurons (1) are not essential for determining nocifensive reflex responsiveness to noxious thermal stimuli, (2) are necessary for full antinociceptive action of morphine (intrathecal or systemic) in these tests, and (3) play a significant role in the endogenous modulation of reflex nocifensive responses to persistent pain in the formalin test. Thus, one would predict that altering the activity of MOR-expressing dorsal horn neurons would be antinociceptive and of interest in the search for new approaches to management of chronic pain.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 02/2008; 28(4):904-13. DOI:10.1523/JNEUROSCI.4452-07.2008 · 6.75 Impact Factor
Article: A case of accidental ricin poisoning[Show abstract] [Hide abstract]
ABSTRACT: A case report of accidental, mild ricin poisoning by ingestion of ten Castor beans by a 70 year old man. The clinical presentation is followed by a discussion about the toxicity of ricin, its use and misuse and the contrast between the toxicity of pure ricin and the ingestion of castor beans. Management of castor bean poisoning is also discussed.
Article: Ribosome-inactivating proteins[Show abstract] [Hide abstract]
ABSTRACT: The main results of the research performed in the last 30 years on ribosome-inactivating proteins (RIPs) are reviewed, with emphasis on the new, controversial and uncertain aspects. The nature, distribution, mechanism of action and properties of these proteins are briefly reported, together with their possible applications. A pattern appears of a still largely unexplored subject, whose role in nature is probably important, and not limited to the biology of plants, since RIPs have been found also in other organisms.Toxicon 10/2004; 44(4):371-83. DOI:10.1016/j.toxicon.2004.05.004 · 2.58 Impact Factor