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Neuroscience Graduate Program at UCSF

Faculty - Jon Levine, M.D./Ph.D.

Signal Transduction and Second Messenger Signaling in Pain Sensory Neurons; CNS Pain Control Mechanisms; Neural-Endocrine Control of Inflammation

Research Description

Our laboratory employs a multidisciplinary approach of molecular, biochemical, in vitro and in vivo electrophysiological and behavioral techniques to evaluate mechanisms underlying pain and analgesia.

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 recently described a novel transducer mechanism for mechanical stimuli. We have also described second messenger pathways mediating nociceptor sensitization in inflammatory and neuropathic pain. The modulation of transduction by opioids is also being investigated, including the mechanisms underlying opioid tolerance and dependence.

We also investigate CNS circuits that mediate analgesia and have recently described a novel analgesia circuit involving limbic pathways as well as sexual dimorphism in pain and analgesic mechanisms.

Finally, we are investigating neural and endocrine (stress axis) contributions to inflammation and the immune response. Our recent work has elucidated a physiological mechanism consisting of a negative feedback inhibition of the inflammatory response, involving neural and endocrine mechanisms.

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Lab Members

Nicole Alessandri-Haber
Associate Research Physiologist,
Ph.D., University Marseille

Oliver Bogen
Postdoctoral Fellow,
Ph.D., Free University Berlin

Elizabeth Joseph
Associate Research Pharmacologist,
Ph.D., U. Bangalore
Neuropathic pain

Paul Green
Adjunct Associate Professor
Ph.D., University of Surrey
Neuroimmune interactions and sexual dimorphism in inflammation and pain

Sachia Khasar
Associate Research Pharmacologist
Ph.D., U. Ibadan
Second messenger signaling in pain sensory neurons

Robert Gear
Associate Researcher
D.D.S., Ph.D., UCSF
Sexual dimorphism in analgesic mechanisms

David Reichling
Associate Research Physiologist
Ionic mechanisms in sensory transduction

Xiojie Chen
Associate Research Physiologist
Ph.D., U. Alicante
Transduction in primary afferent nociceptors

Olyinka Dina
Associate Research Pharmacologist
Ph.D., U. Ibadan
Gender dependent mechanisms in pain

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Selected Publications

Link to Publications via PubMed

Hucho, T. and Levine, J.D. (2007) Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron 55:365-376.

Joseph, E.K., Bogen, O., Alessandri-Haber, N. and Levine, J.D. (2007) PLC-beta 3 signals upstream of PKC epsilon in acute and chronic inflammatory hyperalgesia. Pain 132:67-73.

Levine, J.D. and Alessandri-Haber, N. (2007) TRP channels: targets for the relief of pain. Biochim. Biophys. Acta 1772:989-1003.

McCarter, G.C. and Levine, J.D. (2006) Ionic basis of a mechanotransduction current in adult rat dorsal root ganglion neurons. Mol. Pain 2:28.

Hucho, T.B., Dina, O.A., Kuhn, J. and Levine, J.D.  (2006) Estrogen controls PKCepsilon-dependent mechanical hyperalgesia through direct action on nociceptive neurons. Eur. J. Neurosci. 24:527-534.

Alessandri-Haber, N., Dina, O.A., Joseph, E.K., Reichling, D. and Levine, J.D. (2006) A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators.
J. Neurosci. 26:3864-3874.

Joseph, E.K. and Levine, J.D. (2006) Mitochondrial electron transport in models of neuropathic and inflammatory pain. Pain 121:105-114.

Malik-Hall, M., Dina, O.A. and Levine, J.D. (2005) Primary afferent nociceptor mechanisms mediating NGF-induced mechanical hyperalgesia. Eur. J. Neurosci. 21:3387-3394.

Hucho, T.B., Dina, O.A. and Levine, J.D. (2005) Epac mediates a cAMP-to-PKC signaling in inflammatory pain: an isolectin B4(+) neuron-specific mechanism. J. Neurosci. 25:6119-6126.

Dina, O.A., Hucho, T., Yeh, J., Malik-Hall, M., Reichling, D.B. and Levine, J.D. (2005) Primary afferent second messenger cascades interact with specific integrin subunits in producing inflammatory hyperalgesia. Pain 115:191-203.

Joseph, E.K. and Levine, J.D. (2004) Caspase signalling in neuropathic and inflammatory pain in the rat. Eur. J. Neurosci. 20:2896-2902.

Alessandri-Haber, N., Dina, O.A., Yeh, J.J., Parada, C.A., Reichling, D.B. and Levine, J.D. (2004) Transient receptor potential vanilloid 4 is essential in chemotherapy-induced neuropathic pain in the rat. J. Neurosci. 24:4444-4452.

Dina OA, Parada CA, Yeh J, Chen X, McCarter GC, Levine JD. (2004) Integrin signaling in inflammatory and neuropathic pain in the rat. Eur. J. Neurosci. 19:634-642.

Joseph EK, Parada CA, Levine JD. (2003) Hyperalgesic priming in the rat demonstrates marked sexual dimorphism. Pain 105:143-150.

de Coupade C, Solito E, Levine JD. (2003) Dexamethasone enhances interaction of endogenous annexin 1 with L-selectin and triggers shedding of L-selectin in the monocytic cell line U-937. Br. J. Pharmacol. 140:133-145.

Dina, O.A., McCarter, G.C., de Coupade, C. and Levine, J.D. (2003) Role of the sensory neuron cytoskeleton in second messenger signaling for inflammatory pain. Neuron 39:613-624.

Alessandri-Haber, N., Yeh, J.J., Boyd, A.E., Parada, C.A., Chen, X., Reichling, D.B. and Levine, J.D. (2003) Hypotonicity induces TRPV4-mediated nociception in rat. Neuron 39:497-511.

Strausbaugh, H.J., Green, P.G., Dallman, M.F. and Levine, J.D. (2003) Repeated, non-habituating stress suppresses inflammatory plasma extravasation by a novel, sympathoadrenal dependent mechanism. Eur. J. Neurosci. 17:805-812.

Schmidt, B.L., Tambeli, C.H., Barletta, J., Luo, L., Green, P., Levine, J.D. and Gear, R.W. (2002) Altered nucleus accumbens circuitry mediates pain-induced antinociception in morphine-tolerant rats. J. Neurosci. 22:6773-6780.

Aley, K.O., Martin, A., McMahon, T., Mok, J., Levine, J.D. and Messing, R.O. (2001) Nociceptor sensitization by extracellular signal-regulated kinases.
J Neurosci. 21:6933-6939.

Dina, O.A., Aley, K.O., Isenberg, W., Messing, R.O. and Levine, J.D. (2001) Sex hormones regulate the contribution of PKCepsilon and PKA signalling in inflammatory pain in the rat. Eur. J. Neurosci. 13:2227-2233.

Miao, F.J., Jänig, W. and Levine, J.D. (2000) Nociceptive neuroendocrine negative feedback control of neurogenic inflammation activated by capsaicin in the rat paw: role of the adrenal medulla. J. Physiol. 527:601-610.

Khasar, S.G., Lin, Y.H., Martin, A., Dadgar, J., McMahon, T., Wang, D., Hundle, B., Aley, K.O., Isenberg, W., McCarter, G., Green, P.G., Hodge, C.W., Levine, J.D. and Messing, R.O. (1999) A novel nociceptor signaling pathway revealed in protein kinase C epsilon 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 shedding of L-selectin from neutrophils.
Nat. Med. 5:1057-1061.

Gear, R.W., Aley, K.O. and Levine, J.D. (1999) Pain-induced analgesia mediated by mesolimbic reward circuits. J. Neurosci. 19:7175-7181.

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Jon Levine, M.D./Ph.D.





Office Address

UCSF MC 0440
521 Parnassus Avenue, room C-555
San Francisco, CA 94143

Other Websites

PIBS Website

Dept. of Medicine-Division of Rheumatology

Dept. of Oral and Maxillofacial Surgery