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Method and compositions for treatment of chronic neuropathic pain

a neuropathic pain and composition technology, applied in the field of chronic neuropathic pain treatment methods and compositions, can solve the problems of no scientifically validated treatment for chronic pain, increased incidence of chronic pain, and huge burden on society in both health care and productivity loss

Inactive Publication Date: 2005-09-22
APKARIAN TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0005] The present invention answers this need by providing a method for treating chronic pain in an individual suffering from chronic pain, comprising administering to the individual an amount of a therapeutic comprising glycine receptor agonist or glycine transporter antagonist in an amount effective to treat the chronic pain. In specific embodiments, the therapeutic comprises D-cycloserine and / or sarcosine. The therapeutic may also contain a secondary analgesic such as opiates, NSAIDs, and cox-2 inhibitors.

Problems solved by technology

Treatment of chronic pain is a challenge for physicians and patients since there are no medications that specifically target the condition, and since the medications presently used result in very little relief and are based on their efficacy in acute pain conditions or on their efficacy on relieving secondary effects like anxiety and depression.
Incidence of chronic pain is increasing in society and its burden on society is huge in both health care and lost productivity.
Currently there are no scientifically validated therapies for relieving chronic pain.

Method used

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  • Method and compositions for treatment of chronic neuropathic pain
  • Method and compositions for treatment of chronic neuropathic pain
  • Method and compositions for treatment of chronic neuropathic pain

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0054] Rats with mechanically injured paws were used as models of neuropathic pain. In the test, a weight is applied to the injured paw, and the pain response is assessed. More effective pain control allows the rat to tolerate a greater weight. Rats (groups or 8-10 rats per treatment) were treated with oral saline (control) or 3, 10 or 30 mg / kg of D-cycloserine for a period of two weeks. Pain was monitored from two days before the treatment commenced for a period of 35 days total.

[0055]FIG. 2A shows a graphical representation of the results of this study, with the period of oral treatment with D-cycloserine shown in the shaded region. The open squares represent the control. The black squares represent 30 mg / kg dosage. The two intermediate lines are 3 (lighter) and 10 mg / kg (darker). As can be seen, during the time of treatment, there is a generally dose-dependent response. Post-treatment, the animals show long-lasting analgesia, with a return to initial neuropathy levels at day 35....

example 2

[0060] To model drug-induced pain, rats were treated with cisplatin (2 mg / kg), a common chemotherapy drug. As shown graphically in FIG. 4, after 14 days of treatment, the rats had developed mechanical sensitivity. In the next 14 days of treatment with cisplatin, oral treatment with 30 mg / kg of D-cycloserine, two treatments per day, result in a partial reversal of the mechanical sensitivity (gray bars). In contrast, sensitivity was maintained in rats treated with a saline control (white bars). Thus, in rat models of cisplatin-induced neuropathy, pain behavior decreases 50% in two weeks in animals treated with cycloserine compared with animals treated with placebo.

example 3

[0061]FIG. 5 shows the effects of infusing D-cycloserine (50 μg) into the medial prefrontal cortex (black squares), bilateral amygdala (black triangles), and visual cortex (white triangles) as compared to a saline infusion in the medial prefrontal cortex (white squares) in a rat exhibiting mechanical sensitivity Only medial prefrontal cortex and amygdala infusions result in analgesia.

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Abstract

Chronic pain is treated in an individual suffering from chronic pain by administering to the individual an amount of a therapeutic containing a glycine receptor agonist such as D-cycloserine or a GlyT-1 glycine transporter antagonist such as sarcosine in an amount effective to treat the chronic pain. The therapeutic may also contain a secondary analgesic such as opiates, NSAIDs or cox-2 inhibitors. The analgesic can be formulated in a pharmaceutical composition in the form of an injectable solution that contains at least two different analgesics, at least one of the analgesics of which is a glycine receptor agonist or a GlyT-1 glycine transporter antagonist. Suitable pharmaceutical compositions contain D-cycloserine and / or sarcosine, optionally in combination with opiates, NSAIDs or cox-2 inhibitors.

Description

STATEMENT OF RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application Ser. No. 60 / 555,264, filed Mar. 22, 2004, which application is incorporated herein by reference.STATEMENT CONCERNING GOVERNMENT FUNDING [0002] This invention was made in part with funds from NIH Grants Nos. NS 35115 and NS 42660. The United States Government may have certain rights in the invention.BACKGROUND OF THE INVENTION [0003] This application relates to the use of glycine receptor agonists and glycine transporter antagonists for the treatment of chronic pain. [0004] Treatment of chronic pain is a challenge for physicians and patients since there are no medications that specifically target the condition, and since the medications presently used result in very little relief and are based on their efficacy in acute pain conditions or on their efficacy on relieving secondary effects like anxiety and depression. Incidence of chronic pain is increasing in society and its bur...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/198A61K31/365A61K31/42A61K45/06
CPCA61K31/198A61K31/365A61K31/42A61K45/06A61K2300/00A61P25/04
Inventor APKARIAN, A. VANIA
Owner APKARIAN TECH
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