title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Karolinska Institutet, Pediatric Anesthesia and Intensive Care, Astrid Lindgren Children's Hospital, Karolinska Hospital, Stockholm, Sweden. Margareta.von.heijne@karo.ki.se
authors.forename: M
authors.initials: M
authors.lastname: von Heijne
authors.forename: J X
authors.initials: JX
authors.lastname: Hao
authors.forename: A
authors.initials: A
authors.lastname: Sollevi
authors.forename: X J
authors.initials: XJ
authors.lastname: Xu
authors.forename: Z
authors.initials: Z
authors.lastname: Wiesenfeld-Hallin
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D007278:Injections, Spinal; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000523:psychology; D010660:Phenylisopropyladenosine / Q000008:administration & dosage / Q000627:therapeutic use*; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000701:Analgesics, Opioid; D058906:Purinergic P1 Receptor Agonists; D010660:Phenylisopropyladenosine; D009020:Morphine