HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Sarntinoranont, M. Articles by Morrison, P. F. Search for Related Content PubMed PubMed Citation Articles by Sarntinoranont, M. Articles by Morrison, P. F.

COMPLEX FUNCTIONS OF THE CENTRAL NERVOUS SYSTEM, SLEEP AND LOCOMOTION

Direct interstitial infusion of NK₁-targeted neurotoxin into the spinal cord: a computational model

¹Division of Bioengineering and Physical Science, Office of Research Services, ²Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, and ³Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892

Submitted 7 August 2002 ; accepted in final form 4 March 2003

Convection-enhanced delivery of substance P (SP) nocitoxins to the spinal cord interstitium is under consideration for the treatment of chronic pain. To characterize treatment protocols, a three-dimensional finite-element model of infusion into the human dorsal column was developed to predict the distribution of SP-diphtheria toxin fusion protein (SP-DT') within normal and target tissue. The model incorporated anisotropic convective and diffusive transport through the interstitial space, hydrolysis by peptidases, and intracellular trafficking. For constant SP-DT' infusion (0.1 µl/min), the distribution of cytotoxicity in NK₁ receptor-expressing neurons was predicted to reach an asymptotic limit at 6–8 h in the transverse direction at the level of the infusion cannula tip (60% ablation of target neurons in lamina I/II). Computations revealed that SP-DT' treatment was favored by a stable SP analog (half-life 60 min), high infusate concentration (385 nM), and careful catheter placement (adjacent to target lamina I/II). Sensitivity of cytotoxic regions to NK₁ receptor density and white matter protease activity was also established. These data suggest that intraparenchymal infusions can be useful for treatment of localized chronic pain.

convection-enhanced delivery; intraparenchymal infusions; pain therapy; pharmacodynamic model; convection; finite-element method

This article has been cited by other articles:

				O. Skott Pain: new insights, new treatments? Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R30 - R31. [Full Text] [PDF]