Thomas S. McDowell

Opioid Modulation of Nociceptive Transmission

Research Strengths: Membrane Excitability and Synaptic Transmission, Molecular Neuroscience

Primary nociceptive neurons, whose cell bodies reside in the dorsal root ganglia, transmit noxious sensations from the periphery to neurons in the dorsal horn of the spinal cord. Analgesic agents such as opioids may block nociceptive transmission in the dorsal horn through both presynaptic and postsynaptic effects. Our current research focuses on presynaptic mechanisms of opioid action. Using the whole cell patch clamp technique, we are examining the effects of opioids and other G protein coupled receptor agonists on voltage-gated calcium channels in acutely isolated primary sensory neurons. Heat-sensitive nociceptive neurons are identified in vitro by sensitivity to the TRPV1 receptor agonist capsaicin. The goals of this research project are to identify and characterize different populations of nociceptive neurons with respect to their function, opioid sensitivity, and growth factor dependence using primarily pharmacological and biophysical approaches. We are also interested in sensory neuron excitability and how local anesthetics and opioids influence neuronal activity by interactions with both voltage- and ligand-gated ion channels. Future research projects include the study of postsynaptic effects of opioids and the modulation of spinal nociceptive synaptic pathways by recording from dorsal horn neurons in spinal cord slices.

Selected Publications:

McDowell, T.S. 2004. Exogenous nerve growth factor attenuates opioid-induced inhibition of voltage-activated Ba2+ currents in rat sensory neurons. Neuroscience 125: 1029-1037. [PDF]
McDowell, T.S. 2003. Fentanyl decreases Ca2+ currents in a population of capsaicin responsive sensory neurons. Anesthesiology 98: 223-231. [PDF]
McDowell, T.S., and R.Y. Yukhananov. 2002. HSP90 inhibitors alter capsaicin- and ATP-induced currents in rat dorsal root ganglion neurons. NeuroReport 13: 437-441. [PDF]
Lokuta, A.J., H. Komai, T.S. McDowell, and H.H. Valdivia. 2002. Functional properties of ryanodine receptors from rat dorsal root ganglia. FEBS Lett. 511: 90-96. [PDF]
Komai H.K., and T.S. McDowell. 2001. Local anesthetic inhibition of voltage-activated potassium currents in rat dorsal root ganglion neurons. Anesthesiology 94: 1089-1095. [PDF]


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Thomas S. McDowell Opioid Modulation of Nociceptive Transmission E-mail: tsmcdowe@wisc.edu Research Strengths: Membrane Excitability and Synaptic Transmission, Molecular Neuroscience Primary nociceptive neurons, whose cell bodies reside in the dorsal root ganglia, transmit noxious sensations from the periphery to neurons in the dorsal horn of the spinal cord. Analgesic agents such as opioids may block nociceptive transmission in the dorsal horn through both presynaptic and postsynaptic effects. Our current research focuses on presynaptic mechanisms of opioid action. Using the whole cell patch clamp technique, we are examining the effects of opioids and other G protein coupled receptor agonists on voltage-gated calcium channels in acutely isolated primary sensory neurons. Heat-sensitive nociceptive neurons are identified in vitro by sensitivity to the TRPV1 receptor agonist capsaicin. The goals of this research project are to identify and characterize different populations of nociceptive neurons with respect to their function, opioid sensitivity, and growth factor dependence using primarily pharmacological and biophysical approaches. We are also interested in sensory neuron excitability and how local anesthetics and opioids influence neuronal activity by interactions with both voltage- and ligand-gated ion channels. Future research projects include the study of postsynaptic effects of opioids and the modulation of spinal nociceptive synaptic pathways by recording from dorsal horn neurons in spinal cord slices. Selected Publications: McDowell, T.S. 2004. Exogenous nerve growth factor attenuates opioid-induced inhibition of voltage-activated Ba2+ currents in rat sensory neurons. Neuroscience 125: 1029-1037. [PDF] McDowell, T.S. 2003. Fentanyl decreases Ca2+ currents in a population of capsaicin responsive sensory neurons. Anesthesiology 98: 223-231. [PDF] McDowell, T.S., and R.Y. Yukhananov. 2002. HSP90 inhibitors alter capsaicin- and ATP-induced currents in rat dorsal root ganglion neurons. NeuroReport 13: 437-441. [PDF] Lokuta, A.J., H. Komai, T.S. McDowell, and H.H. Valdivia. 2002. Functional properties of ryanodine receptors from rat dorsal root ganglia. FEBS Lett. 511: 90-96. [PDF] Komai H.K., and T.S. McDowell. 2001. Local anesthetic inhibition of voltage-activated potassium currents in rat dorsal root ganglion neurons. Anesthesiology 94: 1089-1095. [PDF]

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