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Peripheral antihyperalgesic mechanis...

Patwardhan, Amol Madhusudan.

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Peripheral antihyperalgesic mechanisms of opioids and cannabinoids.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Peripheral antihyperalgesic mechanisms of opioids and cannabinoids./
Author:	Patwardhan, Amol Madhusudan.
Description:	179 p.
Notes:	Adviser: Kenneth Hargreaves.
Contained By:	Dissertation Abstracts International67-04B.
Subject:	Health Sciences, Pharmacology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3215138
ISBN:	9780542649899

Peripheral antihyperalgesic mechanisms of opioids and cannabinoids.
Patwardhan, Amol Madhusudan.

Peripheral antihyperalgesic mechanisms of opioids and cannabinoids. - 179 p.

Adviser: Kenneth Hargreaves.

Thesis (Ph.D.)--The University of Texas Health Science Center at San Antonio, 2006.

The subset of peripherally selective analgesics that inhibit sensory transmission at the nociceptor level are an attractive area of research, since such analgesics might exert minimal CNS related side effects. In animal models of pain, both opioids and cannabinoids demonstrate peripherally mediated antihyperalgesia/antinociception. However, the mechanisms behind selective efficacy of peripheral opioids in inflamed tissue and the efficacy of peripheral cannabinoids despite the lack of metabotropic cannabinoid receptors on nociceptors are not clearly understood.

ISBN: 9780542649899Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

Peripheral antihyperalgesic mechanisms of opioids and cannabinoids.
LDR:03560nam 2200301 a 45 001 964036
005 20110901
008 110901s2006 eng d
020 $a 9780542649899
035 $a (UMI)AAI3215138
035 $a AAI3215138
040 $a UMI $c UMI
100 1 $a Patwardhan, Amol Madhusudan. $3 1287109
245 1 0 $a Peripheral antihyperalgesic mechanisms of opioids and cannabinoids.
300 $a 179 p.
500 $a Adviser: Kenneth Hargreaves.
500 $a Source: Dissertation Abstracts International, Volume: 67-04, Section: B, page: 1936.
502 $a Thesis (Ph.D.)--The University of Texas Health Science Center at San Antonio, 2006.
520 $a The subset of peripherally selective analgesics that inhibit sensory transmission at the nociceptor level are an attractive area of research, since such analgesics might exert minimal CNS related side effects. In animal models of pain, both opioids and cannabinoids demonstrate peripherally mediated antihyperalgesia/antinociception. However, the mechanisms behind selective efficacy of peripheral opioids in inflamed tissue and the efficacy of peripheral cannabinoids despite the lack of metabotropic cannabinoid receptors on nociceptors are not clearly understood.
520 $a In the present thesis, three major hypotheses were tested. First, that signaling initiated by the activation of receptors for the inflammatory mediators such as bradykinin and proteases induce functional competence in the metabotropic delta opioid receptor (DOR) to inhibit trigeminal nociceptors and possibly contribute to enhanced peripheral DOR antihyperalgesia in inflamed tissue. Second, that signaling initiated by the activation of ionotropic cannabinoid receptors inhibit trigeminal nociceptors in a calcium-calcineurin dependent fashion and possibly contribute to peripheral cannabinoid antihyperalgesia. Third, that both metabotropic DOR and ionotropic cannabinoid receptor ligands inhibit activation of isolated human nociceptors.
520 $a The results of the studies performed in chapters 2 and 3 demonstrate that in trigeminal sensory neurons, inflammatory mediators such as a B2 agonist (bradykinin) and PAR-2 agonists (eg., SLIGR) enhance inhibitory signaling of metabotropic DOR in a PKC dependent pathway. Moreover, bradykinin evokes trafficking of the DOR to the plasma membrane in a PKC independent fashion. Both of these mechanisms possibly contribute to the enhanced peripheral DOR antihyperalgesia in inflamed tissue. The studies performed in chapter 4 demonstrate that both in the trigeminal and DRG system, the activation of ionotropic cannabinoid receptors inhibits TRPV1 function in a calcium-calcineurin dependent fashion and thus possibly contributes to the peripheral cannabinoid antihyperalgesia. Finally, studies performed in chapter 5 demonstrate that in isolated human pulpal tissue, DOR agonists inhibit nociceptor activation whereas the cannabinoids shows a trend toward inhibition.
520 $a The results from present studies add to our understanding of both metabotropic and ionotropic pathways to inhibit nociceptors that can lead to identification of novel peripherally acting analgesics. Moreover, the results demonstrate a need for different pharmacological strategies in treating inflammatory and noninflammatory pain conditions.
590 $a School code: 0853.
650 4 $a Health Sciences, Pharmacology. $3 1017717
690 $a 0419
710 2 0 $a The University of Texas Health Science Center at San Antonio. $3 1030926
773 0 $t Dissertation Abstracts International $g 67-04B.
790 $a 0853
790 1 0 $a Hargreaves, Kenneth, $e advisor
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3215138