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Systems and Methods to Treat Pain Locally

Inactive Publication Date: 2006-11-09
MEDTRONIC INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0012] Embodiments according to the present invention can treat pain through the local administration of one or more compounds that inhibit the NFκB pathway. Local administration of these compounds helps to prevent unwanted side effects, such as immunosuppression, associated with systemic drug administration.

Problems solved by technology

First, it warns of dangerous environmental stimuli (such as hot or sharp objects) by triggering reflexive responses that end contact with the dangerous stimuli.
Second, if reflexive responses do not avoid dangerous environmental stimuli effectively, or tissue injury or infection otherwise results, acute pain facilitates recuperative behaviors.
In some individuals, however, signals that terminate the immune system response are not effective entirely and pro-inflammatory cytokine activity in the area remains active.
The herniated disc also may damage the nerve root by pinching or compressing it, leading to additional immune system activation in the area.
In those individuals where immune system activation does not abate completely, however, neuropathic pain may result.
Inhibiting the immune system, however, is problematic as a general treatment because it leaves an individual vulnerable to infection and unable to repair tissue injuries effectively.
Thus, treatments that inhibit pro-inflammatory cytokines throughout the body generally are not appropriate except in the most extreme cases of neuropathic pain.
Other pain treatments likewise are not effective or appropriate for treating acute or neuropathic pain caused by pro-inflammatory cytokines.
However, because NFκB is also involved in normal cellular physiology, such as mounting an effective immune response, systemic inhibition of this pathway could result in serious side effects.

Method used

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  • Systems and Methods to Treat Pain Locally
  • Systems and Methods to Treat Pain Locally
  • Systems and Methods to Treat Pain Locally

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0036] Animals were randomly assigned to treatment groups and administered control or test compounds as follows: animals received either vehicle (Phosphate Buffered Saline; PBS), the protein-based TNFα inhibitor, Enbrel® as a positive control (3 mg / kg Immunex Corp., Seattle, Wash.) or sulfasalazine, a small molecule inhibitor of NFκB at a dose of 5 mg / kg or 50 mg / kg.

[0037] Animal behavioral testing was conducted on Days 7, 14 and 21 after CCI. In the thermal hyperalgesia test, animals were placed in the clear plastic chamber of a plantar analgesia instrument and allowed to acclimate to the environment for 15 minutes. After the acclimation period, a radiant (heat) beam source stimulus was applied to the CCI hind paw of each animal. The heat source device was set at an intensity of 50, and a maximum latency period of 15 seconds was set to prevent tissue damage according to the recommendations of the instrument manufacturer. If a paw withdrawal occurred within the 15 second period, an...

example 2

[0039] In a subsequent study, additional lower doses of sulfasalazine were evaluated for their effectiveness as a pain treatment using the CCI model. Specifically, the same methods as described above were used except that sulfasalazine was administered at doses of 5 mg / kg; 1 mg / kg or 0.2 mg / kg. As can be seen in FIG. 3, control animals receiving vehicle showed paw withdrawal latencies averaging an increase of about 45%, 41% and 39% over baseline on test days 7, 14 and 21 respectively. Positive control animals receiving the protein-based TNFα inhibitor, Enbrel® increased paw withdrawal latencies to about 51%, 63% and 62% over baseline on test days 7, 14 and 21 respectively. Again, however, all doses of sulfasalazine increased paw withdrawal latencies on all test days even further (to an average of between about 65% to about 85% over baseline measures on all test days), again suggesting that sulfasalazine and NFκB inhibition can provide an effective pain treatment. Indeed, this data s...

example 3

[0040] The ability of sulfasalazine to inhibit pain was also evaluated using a different sensitivity measure following CCI, namely mechanical (or tactile) allodynia. In this study, mechanical allodynia was determined in reaction to probing with von Frey filaments (Stoelting, Wood Dale, Ill.). Mechanical sensitivity was measured on Days 8, 15 and 22 following CCI by determining the median 50% foot withdrawal threshold for von Frey filaments using the up-down method described in Chaplan et al. (J Neurosci Methods 1994; 54:55) which is incorporated by reference herein for its teachings regarding the up-down method. Rats were placed under a plastic cover (9×9×20 cm) on a metal mesh floor. The area tested was the middle glabrous area between the footpads of the plantar surface of the injured hind paw within the L4 innervation area. The plantar area was touched with a series of 9 von Frey hairs with approximately exponentially incremental bending forces (von Frey values: 3.61, 3.8, 4.0, 4...

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PUM

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Abstract

Disclosed herein are systems and methods for contributing to the local treatment of pain. More specifically, the disclosed systems and methods contribute to the local treatment pain by inhibiting the NFκB family of transcription factors.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of U.S. patent application Ser. No. 10 / 972,157 filed on Oct. 22, 2004 which is incorporated by reference herein in its entirety for all purposes.FIELD OF THE INVENTION [0002] The present invention relates to systems and methods for contributing to the local treatment of pain. More specifically, the systems and methods of the present invention contribute to the local treatment of pain by inhibiting the NFκB family of transcription factors. BACKGROUND OF THE INVENTION [0003] Pain can be divided into two types: acute pain and neuropathic pain. Acute pain refers to pain experienced when tissue is being damaged or is damaged. Acute pain serves at least two physiologically advantageous purposes. First, it warns of dangerous environmental stimuli (such as hot or sharp objects) by triggering reflexive responses that end contact with the dangerous stimuli. Second, if reflexive responses do not avoid dan...

Claims

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Application Information

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IPC IPC(8): A61M31/00A61K31/00A61M37/00A01N61/00
CPCA61K9/0019G01N2800/2842A61K9/1647A61K31/00A61K31/185A61K31/192A61K31/352A61K31/366A61K31/381A61K31/401A61K31/4168A61K31/4402A61K31/498A61M37/0069A61K9/0024A61P25/02A61P25/04A61P29/00A61K9/0085A61M5/14244A61M5/14276
Inventor BURRIGHT, ERIC N.SHAFER, LISA L.MCKAY, BILLZANELLA, JOHN
Owner MEDTRONIC INC
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