Discovering

INDIVIDUAL RESEARCHER

Frank L. Rice , Ph.D.
Professor
e-mail: ricef@mail.amc.edu

Education

1975 - Ph.D. from Johns Hopkins University

Current Research

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). These experiments create abnormal conditions like those that occur in humans such as loss of sensation, painful neuromas, 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 are being explored as potential therapeutic agents for preventing or treating such experimentally induced neuropathologies. In collaboration with neurologists and neuroscientists at Albany Medical College, Harvard University, Johns Hopkins University, 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. Importantly, our recent research has been indicating that cells in the epidermis (keratinocytes) play an important role in detecting and integrating sensory stimulation of the skin. In particular, the keratinocytes contain opiate and cannabinoid related molecules that may normally reduce pain sensation during the normal wear and tear of the skin. Therefore, changes in the epidermal chemistry may also contribute to neuropathic pain. This research indicates that the epidermis may have neuronal properties that may be a potential target for treating chronic pain.

References

1. Albrecht PJ, Hines S, Eisenberg E, Pud D, Finlay DR, Connolly MK, Paré M, Davar G, Rice FL (2006) Pathologic alterations of cutaneous innervation and vasculature in affected limbs from patients with Complex Regional Pain Syndrome. Pain 120:244-266.



2. Fünfschilling U, Ng Y-G, Zang K, Miyazaki JK, Reichardt LF, Rice FL (2004) TrkC kinase expression in distinct subsets of cutaneous trigeminal innervation and nonneuronal cells. J. Comp. Neurol. 480:392-414



3. Ibrahim MM, Porreca F, Lai J, Albrecht PJ, Rice FL, Khodorova A, Davar G, Makriyannis A, Vanderah TW, Mata HP, Malan TP (2005) CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. PNAS 102: 3093-3098.



4. Khodorova A, Navarro B, Murphy J, Rice FL, Mazurkiewicz JE, Long-Woodward D, Stoffel M, Jouaville LS, Strichartz GR, Yukhananov R, Davar G (2003) Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury. Nature Med. 9:1055-1061



5. Zylka MJ, Rice FL, Anderson DJ (2005) Topographically distinct epidermal nociceptive circuits revealed by axonal tracers targeted to Mrgprd. Neuron 45:1-20.