Rethinking multiple sclerosis.

A peroxidase-antiperoxidase immunostaining method was employed to determine the initial stage of appearance and localization of substance P (SP) and enkephalin (ENK) in the nucleus dorsalis of the developing human spinal cord. Both SP- and ENK-positive fibers started to appear from the 10th week of gestation in regions surrounding the nucleus dorsalis. SP-positive fibers then reached the nucleus at 13 weeks and from 26 weeks to term, three strands of SP-positive fibers, which were predominantly originated from the superficial layers of the dorsal horn, penetrated into the nucleus dorsalis from its medial, median and lateral aspects. From 26 weeks onwards, ENK-positive fibers, originated from the superficial and the adjacent layers of the spinal cord, formed a thicker medial and a thinner lateral bundle projecting into the nucleus dorsalis. Our results show that both SP- and ENK-positive fibers started to appear at around 10 weeks and a consistent pattern of immunoreactivity was established by around 26-30 weeks of gestation.

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PubMed2001

Acquired channelopathies in nerve injury and MS.

Although neurophysiologic doctrine has traditionally referred to "the" voltage-gated sodium channel, it is now clear that there are at least nine genes that encode molecularly and physiologically distinct sodium channels. Mutations of sodium channel genes provide a basis for genetic channelopathies. Dysregulated expression of sodium channels due to alterations in activity of nonmutated channel genes, on the other hand, can produce acquired channelopathies. Two examples of acquired channelopathies are discussed in this article. Recent research has established that peripheral nerve injury can provoke an acquired channelopathy in spinal sensory neurons; axonal transection triggers the turning-off of some previously active sodium channel genes and the turning-on of at least one previously silent sodium channel gene, a set of molecular changes that can result in hyperexcitability of these cells. Emerging evidence also suggests that an acquired channelopathy, characterized by abnormal expression of sensory neuron specific sodium channels that can alter impulse trafficking within Purkinje cells, may contribute to the pathophysiology of MS. Subtype-specific drugs that selectively modulate various types of channels probably will soon be developed. The acquired channelopathies associated with nerve injury and MS may thus represent prototype disorders that present therapeutic opportunities.

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