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Methods and compositions using ampk activators for pharmacological prevention of chronic pain

a technology of ampk activator and composition, applied in the field of pain treatment, can solve the problems of nsaids) not always preventing the transition to chronic post-surgical pain, and many patients suffer adverse gastrointestinal discomfort, so as to reduce or prevent the development of pain

Inactive Publication Date: 2018-11-08
THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chronic pain following surgical incisions is a major clinical problem.
Currently available therapeutics given for acute post-surgical pain (e.g., opiates and non-steroidal anti-inflammatory drugs, i.e., NSAIDs) do not always prevent the transition to chronic post-surgical pain.
Moreover, because these drugs are typically administered orally, many patients suffer adverse gastrointestinal discomfort.

Method used

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  • Methods and compositions using ampk activators for pharmacological prevention of chronic pain
  • Methods and compositions using ampk activators for pharmacological prevention of chronic pain
  • Methods and compositions using ampk activators for pharmacological prevention of chronic pain

Examples

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example 1

[0071]Materials and Methods

[0072]Experimental Animals:

[0073]Male ICR mice (Harlan, 20-25 g) were used for the study. All animal procedures were approved by the Institutional Animal Care and Use Committee of The University of Arizona and were in accordance with International Association for the Study of Pain guidelines.

[0074]Behavior Testing:

[0075]For the testing, animals were placed in acrylic boxes with wire mesh floors and allowed to habituate for approximately 1 h on all testing days. Paw withdrawal thresholds were measured using calibrated von Frey filaments (Stoelting, Wood Dale, Ill.) by stimulating the plantar aspect of left hind paw using the up-down method (Chaplan et al., 1994).

[0076]Plantar Incision and Behavioral Testing:

[0077]Prior to surgery all animals were assessed for paw withdrawal thresholds. A mouse model of incisional pain was used for this study (Banik et al., 2006). A 5 mm longitudinal incision was made with a number 11 blade through skin, fascia and muscle of...

example 2

[0096]Case Study

[0097](1) Patient A, a 28 year old female, presents for a scheduled cesarean section. Vial signs and labs appear normal. Obstetrician makes a low transverse incision, and delivery proceeds normally. Approximately 18 hours after surgery, Patient A is administered a sub-efficacious dose of biguanide AMPK activator metformin and a sub-efficacious dose of AMPK activator A769662 to help prevent incision-induced pain such as chronic pain development. Follow up with Patient A regarding incision-induced pain occurs bi-weekly for six weeks post-op. Patient A experiences little incision-induced pain within 5 days post-op, and no pain is observed by 3 weeks post-op.

[0098](2) Patient B, a 55 year-old male, present to surgery for gastric banding surgery. Before anesthesia is initiated, Patient B is administered a sub-efficacious dose of biguanide AMPK activator phenformin and a sub-efficacious dose of AMPK activator leptin to help prevent incision-induced pain such as chronic pai...

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Abstract

Methods and compositions using a combination of adenosine monophosphate protein kinase (AMPK) activators for treating pain such as post-surgical pain or development of chronic pain. The two or more AMPK activators work synergistically and may be administered in individually sub-efficacious doses. The AMPK activators may have different mechanisms of AMPK activation. The AMPK activators may be administered systemically and / or topically in, for example, as a gel, ointment, cream, lotion, suspension, liquid, or transdermal patch.

Description

CROSS REFERENCE[0001]This application is a continuation and claims benefit of U.S. patent application Ser. No. 14 / 956,042 filed Dec. 1, 2015, which is a continuation-in-part and claims benefit of U.S. patent application Ser. No. 14 / 318,245 filed Jun. 27, 2014, now U.S. Pat. No. 9,233,085, which claims priority to and is a non-provisional of U.S. Provisional Patent Application No. 61 / 840,886, filed Jun. 28, 2013, the specification(s) of which is / are incorporated herein in their entirety by reference.GOVERNMENT SUPPORT[0002]This invention was made with government support under Grant No. R01 GM102575 awarded by NIH. The government has certain rights in the invention.FIELD OF THE INVENTION[0003]The present invention relates to methods and compositions for treating pain, more particularly to methods and compositions featuring two (or more) different 5′ adenosine monophosphate-activated protein kinase (AMPK) activators for treating pain, for example post-surgical pain (e.g., pain at an in...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/22A61K31/616A61K38/18A61K38/20A61K31/4439A61K31/4375A61K31/4365A61K31/155A61K38/02A61K31/05A61K31/7056
CPCA61K31/616A61K38/185A61K38/204A61K31/4439A61K31/4375A61K38/2264A61K31/4365A61K31/155A61K38/02A61K31/05A61K31/7056A61K9/0014A61K9/06
Inventor PRICE, THEODORE J.DUSSOR, GREGORYTILLU, DIPTILIAN, BO
Owner THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA
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