A laminar cytoarchitectonic scheme of the lower thoracic and lumbosacral segments of the rat spinal cord is presented in which Rexed's principles for the cat are applied. The material consists of 80-micron-thick sections stained with toluidine blue or according to van Gieson and 2-micron-thick sections stained with p-phenylenediamine or toluidine blue. The cytoarchitectonic organization of the rat spinal cord was found to be basically similar to that of the cat, although certain differences exist--for example, in the extension of the laminae. In addition to the laminar scheme, the distribution of certain cell groups, Lissauer's tract, and the pyramidal tract were investigated.

A laminar cytoarchitectonic scheme of the cervical and upper thoracic segments of the rat spinal cord is presented in which Rexed's principles for the cat are applied. The material examined in the current investigation consists of 50-80 microns-thick unstained or Nissl-stained sections, and 2 microns-thick plastic-embedded sections stained with paraphenylenediamine. The cytoarchitectonic organization was found to be basically similar to that of the cat. As in our previous study of the cytoarchitectonic organization of the lower thoracic and lumbosacral spinal cord (Molander et al.; J. Comp. Neurol. 230:133-141, '84), the borderlines between the laminae were often found to be ambiguous, suggestive of zones of transition rather than sharp borders. In addition to the laminar scheme, the distribution of certain important cell groups, including the column of Clarke, the central cervical nucleus, the lateral cervical nucleus, the lateral spinal nucleus, and the internal basilar nucleus, is described.

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Pain places a devastating burden on patients and society and current pain therapeutics exhibit limitations in efficacy, unwanted side effects and the potential for drug abuse and diversion. Although genetic evidence has clearly demonstrated that the voltage-gated sodium channel, Nav1.7, is critical to pain sensation in mammals, pharmacological inhibitors of Nav1.7 have not yet fully recapitulated the dramatic analgesia observed in Nav1.7-null subjects. Using the tarantula venom-peptide ProTX-II as a scaffold, we engineered a library of over 1500 venom-derived peptides and identified JNJ63955918 as a potent, highly selective, closed-state Nav1.7 blocking peptide. Here we show that JNJ63955918 induces a pharmacological insensitivity to pain that closely recapitulates key features of the Nav1.7-null phenotype seen in mice and humans. Our findings demonstrate that a high degree of selectivity, coupled with a closed-state dependent mechanism of action is required for strong efficacy and indicate that peptides such as JNJ63955918 and other suitably optimized Nav1.7 inhibitors may represent viable non-opioid alternatives for the pharmacological treatment of severe pain.