Marked enhancement of anti-allodynic effect by combined intrathecal administration of the adenosine A1-receptor agonist R-phenylisopropyladenosine and morphine in a rat model of central pain.

Abstract

BACKGROUND:

There is often no satisfactory treatment for chronic pain after spinal cord injury. We have previously reported that intrathecal (i.t.) administration of the adenosine A1-receptor agonist R-phenylisopropyl-adenosine (R-PIA) or the opioid morphine has anti-allodynic effects in a model of presumed chronic central pain after photochemically induced spinal cord injury in rats. In the present study, we set out to investigate the possible interaction between i.t. R-PIA and morphine in spinally injured rats.

METHODS:

Sprague-Dawley rats displaying allodynia-like behaviors to mechanical and cold stimuli after photochemically induced spinal cord injury with minor motor deficits were used. R-PIA and morphine, either alone or in combination, were administered i.t. through an implanted catheter to lumbar spinal cord.

RESULTS:

Cumulative doses of R-PIA or morphine dose-dependently reduced the mechanical allodynia-like behavior, with a threshold of 1 nmol and 1.5 nmol, respectively. When co-administrated, R-PIA and morphine produced marked suppression of mechanical allodynia at doses of 5 pmol and 7.5 pmol, respectively. The effect of i.t. co-administration of R-PIA and morphine on cold allodynia was comparable to i.t. R-PIA alone. The combination of R-PIA and morphine did not increase adverse effects such as motor deficits in comparison to either drug alone.

CONCLUSION:

These results demonstrate a supra-additive interaction between the adenosine A1-receptor agonist R-PIA and morphine to reduce mechanical allodynia-like behavior in rats with chronic spinal cord injury. The combination of R-PIA and morphine administered spinally may be superior to R-PIA or morphine alone for treating such pain.

• Authors: M von Heijne, J X Hao, A Sollevi, X J Xu, Z Wiesenfeld-Hallin
• Journal: Acta anaesthesiologica Scandinavica (Acta Anaesthesiol Scand) Vol. 44 Issue 6 Pg. 665-71 (Jul 2000) ISSN: 0001-5172 [Print] England
• PMID: 10903013 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Purinergic P1 Receptor Agonists
• Phenylisopropyladenosine
• Morphine

Topics

• Analgesics, Opioid (administration & dosage, therapeutic use)
• Animals
• Behavior, Animal (drug effects)
• Dose-Response Relationship, Drug
• Drug Synergism
• Female
• Injections, Spinal
• Morphine (administration & dosage, therapeutic use)
• Pain (drug therapy, psychology)
• Phenylisopropyladenosine (administration & dosage, therapeutic use)
• Purinergic P1 Receptor Agonists
• Rats
• Rats, Sprague-Dawley