Hundreds of thousands of patients each year develop chronic pain and hyperalgesia. Many of these conditions remain poorly treated due to our limited understanding of functional organization in the spinal dorsal horn. Though extracellular studies in intact animals are well suited for defining the complex physiologic systems underlying pain signaling, intracellular studies in reduced preparations are best suited for determination of cellular processes. As a means to advance our understanding of spinal mechanisms of pain encoding we propose that these approaches should be combined. To this end we have adapted whole-cellpatch clamp intracellular recording for use in an intact anesthetized preparation of the rodent dorsal horn. Initial studies with this approach have already revealed new properties of neurons in the superficial spinal lamina. For example, biophysical parameters of spinal neurons were correlated to their profile of responses to peripheral stimuli. Additionally, a novel population of silent dorsal horn cells has been identified with latent responses to cutaneous stimuli that can be activated by membrane depolarization. Thus, in viva whole cell patch clamp in intact animals represents an exciting new approach for the study of cellular mechanisms of sensory integration in the dorsal horn. We propose here to extend our preliminary studies in cells of the superficial lamina, to expand the study to include neurons in deeper spinal lamina, and importantly, to determine the biophysical differences between projection and non-projection neurons. The studies outlined in this application will define the mechanisms by which the biophysical properties of cells influence both their action potential and subliminal excitatory and inhibitory responses to natural cutaneous stimuli. Additionally we will define the ionic bases of the biophysical differences among cells of differing functional classification. Knowledge of this kind is a key to advancing our knowledge of the cellular mechanisms of dorsal horn sensory integration and so will result in a better understanding and improved treatment of acute and chronic pain as well as further our understanding of conscious perception of somatic sensation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS039933-02
Application #
6540237
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Porter, Linda L
Project Start
2001-04-01
Project End
2005-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
2
Fiscal Year
2002
Total Cost
$225,000
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Anesthesiology
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Cata, Juan P; Weng, Han-Rong; Dougherty, Patrick M (2008) The effects of thalidomide and minocycline on taxol-induced hyperalgesia in rats. Brain Res 1229:100-10
Garcia, Jose M; Cata, Juan P; Dougherty, Patrick M et al. (2008) Ghrelin prevents cisplatin-induced mechanical hyperalgesia and cachexia. Endocrinology 149:455-60
Dougherty, Patrick M; Cata, Juan P; Burton, Allen W et al. (2007) Dysfunction in multiple primary afferent fiber subtypes revealed by quantitative sensory testing in patients with chronic vincristine-induced pain. J Pain Symptom Manage 33:166-79
Lee, J I; Verhagen Metman, L; Ohara, S et al. (2007) Internal pallidal neuronal activity during mild drug-related dyskinesias in Parkinson's disease: decreased firing rates and altered firing patterns. J Neurophysiol 97:2627-41
Cata, Juan P; Weng, Han-Rong; Burton, Allen W et al. (2007) Quantitative sensory findings in patients with bortezomib-induced pain. J Pain 8:296-306
Cata, J P; Weng, H R; Lee, B N et al. (2006) Clinical and experimental findings in humans and animals with chemotherapy-induced peripheral neuropathy. Minerva Anestesiol 72:151-69
Weng, H-R; Chen, J H; Cata, J P (2006) Inhibition of glutamate uptake in the spinal cord induces hyperalgesia and increased responses of spinal dorsal horn neurons to peripheral afferent stimulation. Neuroscience 138:1351-60
Weng, Han-Rong; Aravindan, Natarajan; Cata, Juan P et al. (2005) Spinal glial glutamate transporters downregulate in rats with taxol-induced hyperalgesia. Neurosci Lett 386:18-22
Weng, H-R; Dougherty, P M (2005) Response properties of dorsal root reflexes in cutaneous C fibers before and after intradermal capsaicin injection in rats. Neuroscience 132:823-31
Chen, J H; Weng, H-R; Dougherty, P M (2004) Sensitization of dorsal root reflexes in vitro and hyperalgesia in neonatal rats produced by capsaicin. Neuroscience 126:743-51

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