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5NTR. The authors used virtual, or in silico, screening to identify compounds similar to NGF -hairpin loop 1. Four loop 1 mimic (LM11A) compounds had neurotrophic, prosurvival activity in cultured mouse hippocampal neurons. Several criteria supported their action as ligands for monomeric p75NTR. Specifically, the compounds did not promote survival of p75NTR−/− neurons, and they competed with NGF for binding to p75NTR-Fc but not TrkA-Fc. The LM11A compounds also displaced a p75NTR antibody targeted to the neurotrophinbinding domain, and they activated signaling molecules downstream of p75NTR.

3. Nociceptor Stimulation and the fMRI
Belinda Susanne Ruehle, Hermann Otto Handwerker, Jochen Klaus Maria Lennerz, and Ralf Ringler

Ruehle et al. used functional magnetic resonance imaging (fMRI) in 13 willing human subjects to visualize the brain regions that contribute to acute pain versus inflammatory pain and hyperalgesia. Nociceptive sensory neurons, or C-fibers, can be subdivided into polymodal mechano-heat-responsive units (CMH) that respond to mechanical and thermal stimuli, and mechano-insensitive units (CMi) that become sensitive to mechanical stimuli only after inflammation. The authors used low-intensity transcutaneous stimulation (TCS) to selectively activate CMH nociceptors, and stronger intracutaneous stimulation (ICS) to activate CMi neurons. The subjects described TCS-induced pain as "stinging" and ICS-induced pain as "deep," "pounding," or "dull". All subjects found one or both unpleasant. Both stimuli activated known pain-processing brain areas, but each stimulus also activated distinct areas. TCS activated nocifensive motor response centers necessary for an immediate withdrawal response, whereas only ICS increased activity in the posterior cingulate cortex thought to be involved in pain memory and aversion.

4. Cor
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Contact: Sara Harris
sharris@sfn.org
202-962-4000
Society for Neuroscience
16-May-2006


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