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p:
415-476-5108
f: 415-476-6305
e: levine@itsa.ucsf.edu
University
of California, San Francisco
521 Parnassus Avenue
Clinical Sciences Bldg., Rm. C-522, Box 0440
San Francisco, CA. 94143-0440
Dr. Levine received
his PhD (Neuroscience, 1972) from Yale University and his M.D. (1978)
from UCSF. He did postdoctoral fellowships at the University of
California at Berkeley and Stanford University. Dr. Levine did his
training in Rheumatology (under Dr. Jack Stobo) and in Clinical
Pharmacology (under Dr. Henry Bourne) at UCSF. In 1983, he joined
the faculty of the Division of Rheumatology at the University of
California, San Francisco.
Research Interests
My laboratory studies mechanisms underlying pain, analgesia and
inflammatory states. We are investigating signal transduction mechanisms
for mechanical, thermal and chemical stimulus-induced activation
of sensory neurons and mechanisms underlying sensitization of responses
to these stimuli. We have described novel transducer mechanisms
for thermal stimuli. We have also described a second messenger pathway
mediating sensitization. We have demonstrated recently, using knockout
mice, a novel role for the epsilon isoform of PKC in mediating nociception.
We have also recently developed the first in vitro model for study
of mechanical transduction in somatosensory neurons. We are in the
process of developing a model for the development of a propensity
for a chronic inflammatory pain state after a period of resolved
acute inflammation.
We elucidating circuits that mediate analgesia and have described
a novel analgesia circuit involving limbic pathways. Recently we
demonstrated that a sufficiently intense painful stimulus can result
in a prolonged period of heterosegmental antinociception that depends
on mechanisms of the mesolimbic dopaminergic reward pathway.
We are also investigating neural and endocrine contributions to
inflammation and to the immune response. We have elucidated a physiological
mechanism consisting of a negative feedback inhibition of the inflammatory
response, involving neural and endocrine circuits. Shedding of the
neutrophil adhesion molecule L-selectin plays a critical role in
this feedback inhibition as well as action locally of annexin. We
have also recently investigated effects of nicotine on inflammation,
at very low dose, relevant to both smokers and individuals exposed
to secondhand smoke. In a recent study we demonstrated that stress,
when introduced chronically, intermittently, can be a potent modulator
of inflammatory response. The roles of the individual stress axes
(HPA, sympathoadrenal and sympathetic) are investigated.
Finally, we have, in both experimental and clinical studies demonstrated
a profound role of gender and often sex hormones in nociception
and anti-nociception, including that mediated by opioids of different
receptor class. We also have demonstrated marked effects of gender
for the influence of vagal afferent activity on processing of nociceptive
stimuli, both acutely and tonically.
Recent Publications
Gear, R.W., Miaskowski, C., Gordon, N.C., Paul, S.M., Heller, P.H.
and Levine J.D. (1996) Significantly greater analgesia in females
compared to males after kappa-opioids. Nature (Medicine) 2:1248-1250.
Green, P.G., Jänig, W.J. and Levine, J.D. (1997) Negative feedback
neuroendocrine control of inflammatory response in the rat is dependent
on the sympathetic postganglionic neuron. J. Neurosci. 17:3234-3238.
Caterina, M.J., Schumacher, M., Tominaga M, Rosen, T.A., Levine,
J.D. and Julius, D.J. (1997) The capsaicin receptor: A heat-activated
ion channel in the pain pathway. Nature 389:816-824.
Gear, R.W. and Levine, J.D. (1998) Pain-induced analgesia by mesolimbic
reward circuits. J. Neurosci. 19:7175-7181.
Green, P.G., Dahlqvist, S.R., Isenberg, W.M., Strausbaugh, H.J.,
Miao, F. J.-P. and Levine, J.D. (1999) Sex steroid regulation of
the inflammatory response: sympathoadrenal dependence in the female
rat. J. Neurosci. 19:4082-2089.
Khasar, S.G., Lin, Y.-H., Martin, A., Dadgar, J., McMahon, T., Hundle,
H., Aley, K.O., Isenberg, W., McCarter, G., Green, P.G., Levine,
J.D. and Messing, R.O. (1999) A novel nociceptive signaling pathway
demonstrated in PKCe-mutant mice. Neuron 24: 253-260.
Strausbaugh, H.J., Green, P.G., Lo, E., Tangemann, K., Reichling,
D.B., Rosen, S.D. and Levine, J.D. (1999) Painful stimulation suppresses
joint inflammation by inducing L-selectin shedding from neutrophils.
Nature Med. 5:1057-1061.
Schumacher, M.A., Moff, I., Sudanagunta, S.P. and Levine, J.D. (2000)
Molecular cloning of an N-terminal splice variant of the capsaicin
receptor. J. Biol. Chem. 275:2756-2762.
Miao, F.,J.-P., Jänig, W. and Levine, J.D. (2000) Nociceptive
neuroendocrine feedback control of neurogenic inflammation activated
by capsaicin in the rat paw: role of the adrenal medulla. J. Physiol.
(Lond.) 527:601-610.
Miao, F.J.-P., Jänig, W., Jasmin, L. and Levine, J.D. (2001)
Spino-bulbo-spinal pathway mediating vagal modulation of nociceptive-neuroendocrine
control of inflammation in the rat. J. Physiol. (Lond.) 532:811-822.
Green, P.G., Dahlqvist, S.R., Isenberg, W.M., Miao, F.J.-P. and
Levine, J.D. (2001) Role of adrenal medulla in development of sexual
dimorphism in inflammation. Eur. J. Neurosci. 14:1436-1444.
Dina, O.A., deCoupade, C., McCarter, G.C. and Levine, J.D. (2003)
Involvement of the sensory neuron cytoskeleton in second messenger
signaling for inflammatory pain. Neuron 39:613-624.
Parada, C.A., Yeh, J.J., Joseph, E.K. and Levine, J.D. (2003) Tumor
necrosis factor receptor type I in sensory neurons contributes to
induction of chronic enhancement of inflammatory hyperalgesia in
rats. Eur. J. Neurosci. 17:1847-1852.
Alessandri-Haber, N., Yeh, J.J., Boyd, A.E., Parada, C.A., Chen,
X.-J., Reichling, D.B. and Levine, J.D. (2003) Hypotonicity induces
TRPV4-mediated nociception in the rat. Neuron 39:497-511.
Miao, F.J.-P., Green, P.G.
and Levine, J.D. (2004) Mechano-sensitive duodenal afferents contribute
to vagal modulation of inflammation in the rat. J. Physiol. (Lond.)
554:227-235.
Dina, O.A., Parada, C.A., Yeh, J., Chen, X.-J., McCarter, G. and
Levine, J.D. (2004) Integrin signaling in inflammatory and neuropathic
pain in the rat. Eur. J. Neurosci. 19:634-642.
Joseph, E.K. and Levine J.D. (2004) Caspase signaling in neuropathic
and inflammatory pain in the rat. Eur. J. Neurosci. 20:2896-2902.
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