IngentaConnect Marked enhancement of anti-allodynic effect by combined intrathec...

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.

Keywords: Pain: central, allodynia, neuropathic; spinal cord: interaction, potentiation; analgesics: adenosine, morphine; anesthetic technique: spinal

Language: English

Document Type: Original article

Affiliations: 1: Karolinska Institutet, Pediatric Anesthesia and Intensive Care, Astrid Lindgren Children's Hospital, Karolinska Hospital, Stockholm, 2: Department of Medical Laboratory Sciences and Technology, Division of Clinical Neurophysiology and 3: Department of Anesthesia and Intensive Care, Huddinge University Hospital, Huddinge, Sweden

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

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