A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 176

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 1034
Function: getPubMedXML

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3152
Function: GetPubMedArticleOutput_2016

File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

Antisense oligonucleotide knockdown of mGlu₅ receptor attenuates the antinociceptive tolerance and up-regulated expression of spinal protein kinase C associated with chronic morphine treatment. | LitMetric

AI Article Synopsis

  • The mGlu₅ receptor plays a critical role in the development of morphine tolerance, affecting pain response in the spinal cord.
  • An antisense oligodeoxynucleotide (ODN) was used to decrease the expression of the mGlu₅ receptor in rats, which resulted in a significant reduction of tolerance to morphine.
  • This treatment also prevented the increase of spinal protein kinase C (PKC) levels associated with morphine tolerance, indicating that mGlu₅ receptor modulation may offer a pathway to reduce tolerance in pain management.

Article Abstract

Spinal metabotropic glutamate receptor 5 (mGlu₅ receptor) is known to influence the development of intrathecal morphine antinociceptive tolerance. However, the signaling mechanisms remain unknown. We carried out intrathecal administration of an antisense oligodeoxynucleotide (ODN), which results in reduced expression of spinal mGlu₅ receptor, to determine its effects on morphine tolerance and spinal protein kinase C (PKC) expression. Rats were treated intrathecally with saline, morphine, mGlu5 receptor antisense ODN or mGlu5 receptor mismatched ODN. Behavioral tests were used to test the thermal and mechanical pain thresholds. Eight days later, rats were sacrificed and spinal cords were harvested to assess the expression of spinal PKC (α, γ and ε) by Western blotting and real-time polymerase chain reaction (PCR). Compared to control, intrathecal mGlu₅ receptor antisense ODN resulted in a ~53.9% reduction of spinal mGlu₅ receptor after 8days treatment. The mGlu5 receptor antisense ODN prevented the development of morphine tolerance. Expression of spinal PKC (α, γ and ε) was up-regulated at the mRNA and protein levels during the development of tolerance. Meanwhile, antisense ODN but not mismatched ODN reduced the spinal dorsal horn levels of PKC (α, γ and ε) which had been up-regulated after morphine exposure. We conclude that mGlu₅ receptor participates in the development of morphine tolerance. Expression of spinal PKC (α, γ and ε) at the mRNA and protein levels increased during morphine tolerance. Antisense ODN of mGlu₅ receptor prevented the tolerance and inhibited the altered expression of spinal PKC (α, γ and ε) during the development of tolerance.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2012.02.046DOI Listing

Publication Analysis

Top Keywords

mglu₅ receptor
28
expression spinal
24
antisense odn
20
morphine tolerance
16
spinal pkc
16
mglu5 receptor
12
receptor antisense
12
receptor
11
spinal
11
tolerance
9

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!