Korean J Anesthesiol.  2002 Jun;42(6):823-830. 10.4097/kjae.2002.42.6.823.

The Interaction of Morphine and Adenosine Receptor Agonists on Antiallodynia in Rats with a Nerve Ligation Injury

• Lee JR
• Kim YK
• Choi DK
• Park JY
• Kwak MJ
• Hwang JH

• KMID: 2032001
• DOI: http://doi.org/10.4097/kjae.2002.42.6.823

Abstract

BACKGROUND: A Nerve ligation injury may produce a pain syndrome that includes tactile allodynia. Reversal effects on tactile allodynia have been demonstrated after an intrathecal administration of adenosine analogues or morphine. Adenosine receptor agonists have been known to have antinociceptive and antiallodynic effects in many animal and human studies. We examined the drug interactions between morphine and adenosine agonists in a rat model of a nerve ligation injury.
METHODS
Male Sprague Dawley rats were prepared with a tight ligation of the left lumbar 5 th and 6 th spinal nerves and chronic lumbar intrathecal catheter implantation for drug administration. We measured the tactile allodynia by applying von Frey filaments ipsilateral to the lesioned hindpaw. Thresholds for paw withdrawal were assessed. Morphine (1 - 30ng), adenosine (1 - 30ng) and R-PIA (0.1 - 10ng) were administered to obtain the dose-response curves and the 50% effective dose (ED50). Fractions of ED50 values were administered to establish the ED50 of drug combinations. Drug interactions were evaluated by the fractional and isobolographic analyses. Allodynic thresholds for left lesioned hindpaw withdrawal to the von Frey hairs test were assessed and converted to % maximal possible effect (%MPE).
RESULTS
The antiallodynic effect of morphine, adenosine, and R-PIA were produced in a dose dependent manner. The antiallodynic effects of combinations showed a similar pattern. Isobolographic analysis revealed a synergistic interaction for the morphine-R-PIA combination but not for the morphine-adenosine combination. However, fractional analysis produced a synergistic result for two combination groups.
CONCLUSIONS
The results demonstrated that intrathecal co-administration of adenosine A1 receptors agonist and morphine showed the synergistic effect on nerve ligation injury induced allodynia.

Keyword

Adenosine; allodynia; drug interaction; intrathecal injection; morphine; R-PIA

MeSH Terms

Adenosine*
Animals
Catheters
Drug Combinations
Drug Interactions
Hair
Humans
Hyperalgesia
Injections, Spinal
Ligation*
Male
Models, Animal
Morphine*
Purinergic P1 Receptor Agonists*
Rats*
Rats, Sprague-Dawley
Receptor, Adenosine A1
Receptors, Purinergic P1*
Spinal Nerves
Adenosine
Drug Combinations
Morphine
Purinergic P1 Receptor Agonists
Receptor, Adenosine A1
Receptors, Purinergic P1