BMCB-Faculty Research, Josephine Lai

Professor of Pharmacology and Molecular & Cellular Biology
Ph.D., Imperial College, University of London, 1985

Pharmacology of neuropathic pain, using nerve ligation injury in the rat as a model.

Research Interests

Spinal Dynorphin and Neuropathic Pain
Dynorphin is a neuropeptide that has unusual properties. It is structurally and pharmacologically defined as an endogenous opioid peptide that inhibits neuronal activity, yet at higher doses it is excitotoxic and induces long lasting abnormal pain. We have extensively characterized the neuronal excitatory actions of dynorphin by pharmacological, physiological and anatomical approaches, and are leaders in the elucidation of the mechanisms of action of dynorphin in chronic pain. The significance of these studies hopefully will pave the way to new therapeutics for the treatment of chronic pain based on dynorphin and its receptors as therapeutic targets.

Sodium Channels and Neuropathic Pain
Sodium channel activity is fundamental to the function of all neurons. Abnormal activity of these channels is critical to the development of chronic pain upon nerve injury. The utility of sodium channel blockers in chronic pain management is limited by severe side effects. We have established compelling evidence that one of the sodium channel sub-types, NaV1.8, is a potential therapeutic target as a selective blockade of this channel is sufficient to block abnormal pain. Because its expression is restricted to peripheral sensory neurons, drugs that are selective blockers for this channel should be effective with no central side effects.

Select Publications

Any link on the below references will take you off of the BMCB site and to an abstract of that particular paper.

Agnes, R.S., Y.S. Lee, P. Davis, S.W. Ma, H. Badghis, F. Porreca, J. Lai, and V.J. Hruby. 2006. Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors. Journal of Medicinal Chemistry 49: 2868-2875.

Gardell, L.R., t. King, M.H. Ossipov, K.C. Rice, J. Lai, T.W. Vanderah, and F. Porreca. 2006. Opioid receptor-mediated hyperalgesia and antinociceptive tolerance induced by sustained opiate delivery. Neuroscience Letters 396: 44-49.

Dogrul, A., E.J. Bilsky, M.H. Ossipov, J. Lai, and F. Porreca. 2005. Spinal L-type calcium channel blockade abolishes opioid-induced sensory hypersensitivity and antinociceptive tolerance. Anesthesia and Analgesia 101: 1730-1735.

King, T., M.H. Ossipov, T.W. Vanderah, F. Porreca, and J. Lai. 2005. Is paradoxical pain induced by sustained opioid exposure an underlying mechanism of opioid antinociceptive tolerance? Neurosignals 14: 194-205.

Luo, M.C., D.Q. Zhang, S.W. Ma, Y.Y. Huang, S.J. Shuster, F. Porreca, and J. Lai. 2005. An efficient intrathecal delivery of small interfering RNA to the spinal cord and peripheral neurons. Molecular Pain 1: 29.

King, T., L.R. Gardell, R. Wang, A. Vardanyan, M.H. Ossipov, T.P. Malan Jr, T.W. Vanderah, S.P. Hunt, V.J. Hruby, J. Lai, and F. Porreca. 2005. Role of NK-1 neurotransmission in opioid-induced hyperalgesia. Pain 116: 276-288.

Ossipov, M.H., J. Lai, T. King, T.W. Vanderah, and F. Porreca. 2005. Underlying mechanisms of pronociceptive consequences of prolonged morphine exposure. Biopolymers 80: 319-324.

Xie, J.Y., D.S. Herman, C.O. Stiller, L.R. Gardell, M.H. Ossipov, J. Lai, F. Porreca, and T.W. Vanderah. 2005. Cholecystokinin in the rostral ventromedial medulla mediates opioid-induced hyperalgesia and antinociceptive tolerance. Journal of Neuroscience 25: 409-416.

Ossipov, M.H., J. Lai, T. King, T.W. Vanderah, T.P. Malan Jr, V.J. Hruby, and F. Porreca. 2004. Antinociceptive and nociceptive actions of opioids. Journal of Neurobiology 61: 126-148.

Chen, Q., T. King, T.W. Vanderah, M.H. Ossipov, T.P. Malan Jr, J. Lai, and F. Porreca. 2004. Differential blockade of nerve injury-induced thermal and tactile hypersensitivity by systemically administered brain-penetrating and peripherally restricted local anesthetics. The Journal of Pain 5: 281-289.

Vanderah, T.W., C.D. Schteingart, J. Trojnar, J.L. Junien, J. Lai, and P.J. Riviere. 2004. FE200041 (D-Phe-D-Phe-D-Nle-D-Arg-NH2): A peripheral efficacious kappa opioid agonist with unprecedented selectivity. The Journal of Pharmacology and Experimental Therapeutics 310: 326-333.

Lai J., F. Porreca, J.C. Hunter, and M.S. Gold. 2004. Voltage-gated sodium channels and hyperalgesia. Annual Review of Pharmacology and Toxicology 44: 371-397.

Contact Information

Mailing:
Josephine Lai, Professor
Department of Pharmacology
University of Arizona
Life Sciences North 563
P. O. Box 210221
Tucson, AZ 85721-0221

Telephone:
520-626-2147 (Office)
520-626-2149 (Lab)

Fax:
520-626-4182

Email:
lai@email.arizona.edu

Please e-mail any comments to:
bmcb@email.arizona.edu