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Method of Inhibiting Chronification of Pain

a technology of chronification and pain, applied in the field of tapentadol, can solve the problems of confusion of evidence for the effect of different anaesthesiology and analgesic regimens on chronic pain after surgery, prolonging pain sensation, and reducing pain in patients, so as to reduce neuropathic pain and facilitate the treatment and inhibition of migrain

Inactive Publication Date: 2012-12-06
GRUNENTHAL GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0022]Further, it has been surprisingly found that tapentadol is useful in the treatment and inhibition of migraine. In contrast to most analgesic drugs which differently reduce neuropathic pain in cephalic versus extracephalic territories, tapentadol has been found equally effective in both territories. Its effect surprisingly involves synergy between the two pharmacological actions of tapentadol, particularly at cephalic level.

Problems solved by technology

In consequence, pain sensation last longer than would typically be expected in view of progressing postoperative wound healing; even though wound healing has been nearly completed, the patient still suffers from pain.
Unfortunately, the evidence for the effect of different anaestetic and analgesic regimens on chronic pain after surgery is confused.
There are also studies, however, that have not shown benefit.
Several studies have looked at multimodal analgesic techniques and the use of drugs such as gabapentin, venlafaxine, and ketamine, but once again the results are not consistent (cf.
It is known that conventional opioid analgesics can detrimentally influence the development of chronic pain.
Thus, as far as the inhibition of postoperative hyperalgesia in mice is concerned, morphine does have no advantageous effect or even is disadvantageous.
Neuropathic pain is a major problem for clinicians, as available treatments produce incomplete pain relief, and have dose-limiting side effects.
Besides, neuropathic pain in territories innervated by the trigeminal system (“cephalic” territories) is even more difficult to treat than that in other parts of the body (“extracephalic” territories).
However, all these models concerned neuropathic pain in extracephalic territories, and none is known yet regarding the potential antiallodynic / antihyperalgesic effects of tapentadol in cephalic territories.

Method used

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  • Method of Inhibiting Chronification of Pain
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  • Method of Inhibiting Chronification of Pain

Examples

Experimental program
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Effect test

example 1

Paw Incision Model for Postoperative Pain

[0111]Post operative, incisional pain is a common form of persistent, acute pain. Brennan et al. (Brennan T J, Vandermeulen E P, and Gebhart G F. Characterization of a rat model of incisional pain. Pain 1996; 64:493-501) developed a post operative model in rats with surgical intervention on the plantar surface of the hind foot for the evaluation of novel analgesic therapeutics. A surgical incision of the rat foot causes a reliable and quantifiable tactile hypersensitivity during the initial post operative period and lasting for several days after surgery. This model may thus be useful for predicting analgesia by investigational agents for post operative pain.

[0112]The experiments were carried out in male albino rats (Sprague Dawley) with 170 g-230 g body weight from a commercial breeder (Charles River, Germany). Surgery was performed as previously described. Brennan et al. (Brennan T J, Vandermeulen E P, and Gebhart G F. Characterization of a...

example 2

Respective Effects of Tapentadol on Mechanical Allodynia / Hyperalgesia in Rats with Ligatures of the Infraorbital Nerve Versus the Sciatic Nerve

Methods

[0120]Male Sprague-Dawley rats (Charles River Laboratories, L′Arbresle, France), weighing 150-200 g on arrival, were used. Animals were maintained under controlled environmental conditions (22±1° C., 60% relative humidity, 12 h / 12 h light / dark cycle, food and water ad libitum) starting from reception in the laboratory, for at least 1 week before any intervention or treatment and thereafter, until euthanasia.

Chronic Constriction Injury to the Infraorbital Nerve (CCI-ION)

[0121]Rats were anaesthetized with sodium pentobarbital (50 mg / kg i.p.). Unilateral CCI-ION was performed under direct visual control using a Zeiss microscope (10-25×). Briefly, the head was fixed in a Horsley-Clarke stereotaxic frame and a midline scalp incision was made, exposing skull and nasal bone. The edge of the orbit, formed by the maxillary, frontal, lacrimal, a...

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Abstract

The use of tapentadol in the treatment of pain and / or pain chronification in a subject suffering from pain chronification and / or in the treatment of pain and inhibition of pain chronification in a subject suffering from pain and at risk of pain chronification, as well as the use of tapentadol for the treatment or inhibition of migraine.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority based on U.S. provisional patent application Nos. 61 / 471,919 and 61 / 480,621, filed Apr. 5, 2011 and Apr. 29, 2011, respectively, the entire disclosures of each of which are incorporated herein by reference. Priority is also claimed based on European patent application nos. EP 11 002 811.5 and EP 11 003 508.6, filed Apr. 5, 2011 and Apr. 29, 2011, respectively, the entire disclosures of each of which are likewise incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]The invention relates to tapentadol for use in the treatment of pain in a subject suffering from pain chronification and / or for use in the treatment or the inhibition of pain chronification. The invention also relates to tapentadol for use in the treatment or inhibition of migraine, i.e. of migraine-related pain, and headache-related pain.[0003]Tapentadol (CG5503), the chemical name for which is (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/135A61P25/06A61P29/00
CPCA61K31/137A61P1/04A61P19/00A61P21/00A61P25/00A61P25/06A61P29/00A61P43/00A61P25/04A61K9/0053
Inventor SCHIENE, KLAUSSTEIGERWALD, IIONAHAMON, MICHELSCHNEIDER, JOHANNESREINARTZ, SILVIAJAHNEL, ULRICHTZSCHENTKE, THOMAS
Owner GRUNENTHAL GMBH
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