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Acute
and chronic injuries and diseases of the nerve supply to the skin and
blood vessels are a major health problem that will afflict most people
at sometime during their lives. Dr. Rice's laboratory is engaged in an
extensive multinational collaboration that is: 1) elucidating the
details of normal and pathological skin and vascular innervation, and
2) assessing the role of nerve growth factor (NGF) and other
neurotrophins (BDNF, NT-3, NT-4) in the development, maintenance and
repair of this innervation.
A powerful animal model being used in this research is the innervation
to the snouts of mice and rats which have a reproducible array of
highly organized whisker follicles. Each follicle is densely innervated
by a wide variety of predictably organized sensory and autonomic nerve
endings. The impact on this innervation is being investigated in mice
that have mutations eliminating the neurotrophins, their high affinity
tyrosine kinase receptors (trkA, trkB, trkC) or their low affinity
receptor (p75). The impact of neurotrophin overproduction is also being
examined in transgenic mice.
Other studies in Dr. Rice's
laboratory are investigating the impact on the whisker and digit
(fingers and toes) innervation due to: 1) nerve damage and
regeneration, 2) induced and naturally occurring diabetes and 3)
treatment with selective neurotoxins (e.g. guanethidine and capsaicin)
or chemotherapeutic agents (e.g. taxol and vinblastine). These
experiments create abnormal conditions like those that occur in humans
such as loss of sensation, painful neuromas, trigeminal neuralgia (tic
douloureux), diabetic neuropathy, complex regional pain syndrome
(reflex sympathetic dystrophy) and chemotherapy-related neuropathy.
Based on the results of the research in the mutant mice, the
neurotrophins will be explored as potential therapeutic agents for
preventing or treating such experimentally induced neuropathologies.
In collaboration with neurologists at Albany Medical College, Harvard
University, Johns Hopkins University, Virginia Medical School and the
University of California at San Francisco, Dr. Rice's expertise gained
from animal studies is being applied to assess the skin innervation of
human patients suffering from the acute pain of herpes zoster attacks
(shingles) and subsequent chronic debilitating pain (postherpetic
neuralgia) as well as diabetic neuropathy and complex regional pain
syndrome. Eventually treatments developed in the animal studies may be
used to treat such patients.
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