Department of Pharmacology

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My laboratory is interested in understanding and developing new treatments for chronic 'neuropathic' pain. Acute tissue injury produces 'nociceptive' pain. Because it promotes avoidance of tissue damage, this unpleasant, yet vital physiological response ensures an individual's survival . By contrast, 'neuropathic' pain induced by injury to, or disease of, the nervous system is a major health problem. Because it persists for months or years after any injury has healed, neuropathic pain serves no obvious biological purpose. It is associated with diabetic, postherpetic and HIV-related neuropathies, as well as with traumatic nerve, brain or spinal cord injury. The prevalence of neuropathic pain has been estimated at 1.5% within the general population. This would mean about 100,000,000 people worldwide! Standard pharmacological interventions include opioids, ketamine, amitryptyline, gabapentin, pregabalin or other anticonvulsants. All too frequently however, these drugs display limited effectiveness or dose-limiting side effects that range from sedation and dizziness to psychosis and hallucinations.

In my laboratory, we try to meet the urgent need for new therapies by understanding the long-term electrophysiological changes that occur in sensory and spinal nerves when they are damaged. This involves altered responsiveness to analgesic and other drugs as well as alterations in ion channel properties and neurotransmitter actions. Experiments are done using whole-cell patch clamp recordings from the cell bodies of sensory nerves in rat dorsal root ganglia as well as `slice-patch' recordings from the dorsal horn of the spinal cord. The latter are complimented using confocal Ca2+ imaging experiments in collaboration with Dr. Klaus Ballanyi (Department of Physiology) and behavioural and biochemical studies in collaboration with Drs. Bradley Kerr (Anesthesiology and Pain Medicine) and Elena Posse de Chaves (Pharmacology).

We have recently developed an organotypic culture system of spinal cord which allows us to put "pain in a dish" and explore its molecular and cellular mechanisms. We also consider the involvement of non-neuronal cells such as microglia and astrocytes in the development of chronic pain. Current projects involve 1) exploring the role of brain derived neurotrophic factor in the onset of chronic neuropathic pain 2) elucidating the mechanism of action of gabapentin, one of the first line drugs in the treatment of neuropathic pain 3) exploring the role of inflammatory mediators such as the interleukins in the development of chronic pain 4) in collaboration with Dr. Christopher Power (Neurology) exploring the role of viral proteins in the development of AIDs related pain.

Stemkowski, PL. & Smith, PA. Long-term IL-1beta exposure causes subpopulation-dependent alterations in rat dorsal root ganglion neuron excitability. J Neurophysiol. 107: 1586-1597 (2012).

Stemkowski, PL. & Smith PA. Sensory neurons, ion channels, inflammation and the onset of neuropathic pain. Can J Neurol Sci. 39: 416-435 (2012).

Shaona Acharjee, Farshid Noorbakhsh, Patrick L. Stemkowski, Camille Olechowski, Éric A.Cohen, Klaus Ballanyi, Bradley Kerr, Carlos Pardo, PETER A. SMITH and Christopher Power. HIV-1 viral protein R causes peripheral nervous system injury associated with in vivo neuropathic pain. FASEB J. 2010 244343-53. PMID: 20628092

Yishen Chen, Sridhar Balasubramanyan, Aaron Y. Lai, Kathryn G. Todd and PETER A. SMITH Effects of Sciatic Nerve Axotomy on the Electrophysiological Characteristics of Various Types of Substantia gelatinosa Neuron. J. Neurophysiology 102: 3203-3215 (2009) PMID: 19793881.

Van B. Lu, James E. Biggs, Martin J. Stebbing, Sridhar Balasubramanyan, Kathryn Todd, Aaron Lai, William F. Colmers, David Dawbarn, Klaus Ballanyi and Peter A. Smith BDNF Drives the Changes in Excitatory Synaptic Transmission in the Rat Superficial Dorsal Horn that Follow Sciatic Nerve Injury. J.Physiol. 587: 1013-1032 (2009) PMID: 19124536.

Sabrina L. Gustafson-Vickers, Van B. Lu, Aaron Y. Lai, Kathryn G. Todd, Klaus Ballanyi and PETER A. SMITH Long-term Actions of Interleukin-1b on Delay and Tonic Firing Neurons in Rat Superficial Dorsal Horn and their Relevance to Central Sensitization. Molecular Pain 4 :63 (2008)PMID: 19091115.

Van B Lu, Klaus Ballanyi, William F Colmers and PETER A. SMITH Neuron type-specific effects of brain-derived neurotrophic factor in rat superficial dorsal horn and their relevance to "central sensitization" J.Physiol. 584: 543-563 (2007) PMID: 17761774.