Korean J Anesthesiol.  2007 Feb;52(2):212-218. 10.4097/kjae.2007.52.2.212.

The Effects of Intrathecal Adenosine A1 Receptor Agonists (R-PIA) on the Morphine Tolerance in a Rat Model of Postoperative Pain

• Jun IG
• Piao LZ
• Kwon MY
• Park JY

• KMID: 2236625
• DOI: http://doi.org/10.4097/kjae.2007.52.2.212

Abstract

BACKGROUND
Analgesic tolerance to opioids has been described in both experimental and clinical conditions, which may limit their clinical utility. This study investigated the effects of intrathecal adenosine A1 receptor agonist (R-PIA) on spinal morphine tolerance.
METHODS
SD rats were given intrathecal injections of saline 10microliter, R-PIA 10microgram, morphine 10microgram, or R-PIA plus morphine combinations for 7 days (R-PIA given for days 1-7; days 1-3; or days 5-7). Antiallodynic testing using von Frey filaments was carried out before and 30 minutes after the drug injection. On day 8, an antiallodynic dose-response curve was constructed and the 50% effective dose (ED(50)) for morphine (given alone) was calculated for each study group.
RESULTS
The coinjection group of R-PIA with morphine blocked the development of tolerance, as shown by the preservation of morphine antiallodynia over 7 days the concomitant decrease in the ED(50) values on day 8, compared with the morphine-alone group. Although additive analgesia over days 1-7 cannot be ruled out, the reductions of the ED(50) in the R-PIA and morphine combination group suggest some suppression of tolerance.
CONCLUSIONS
These results suggest that intrathecal R-PIA prevents the development of spinal opioid tolerance. Future studies will be needed to examine the respective roles of supraspinal and peripheral sites of R-PIA and morphine interaction, and to investigate the mechanisms underlying the action of R-PIA on opioid tolerance.

Keyword

allodynia; intrathecal; morphine; postoperative pain; R-PIA; tolerance

MeSH Terms

Adenosine A1 Receptor Agonists*
Adenosine*
Analgesia
Analgesics, Opioid
Animals
Hyperalgesia
Injections, Spinal
Models, Animal*
Morphine*
Pain, Postoperative*
Rats*
Receptor, Adenosine A1*
Adenosine
Adenosine A1 Receptor Agonists
Analgesics, Opioid
Morphine
Receptor, Adenosine A1