Adenosine A1 receptor agonists reduce hyperalgesia after spinal cord injury in rats.
METHODS
An in vivo study using a spinal cord compression model in rats.


OBJECTIVE
To evaluate the effect of adenosine on thermal hyperalgesia after spinal cord injury (SCI).


BACKGROUND
After SCI, some patients suffer dysesthesia that is unresponsive to conventional treatments. We previously established a rat thoracic spinal cord mild-compression model by which we were able to induce thermal hyperalgesia in the hind limbs.


METHODS
The thoracic spinal cord was compressed gently using a 20-g weight for 20 min. The withdrawal latency in response to thermal stimulation was monitored bilaterally in the hind limbs using Hargreaves' Plantar test apparatus.


RESULTS
SCI-induced thermal hyperalgesia was mimicked by the intrathecal application of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist. Hyperalgesia induced by SCI was significantly inhibited by the intrathecal application of 10-30 nmol chloro-adenosine (Cl-adenosine), a nonselective adenosine receptor agonist. The effect of Cl-adenosine (10 nmol) on hyperalgesia after SCI was blocked by the simultaneous application of DPCPX. Intrathecal application of R(-)N6-(2phenylisopropyl) adenosine (R-PIA; 10 nmol), a selective A1 receptor agonist, also inhibited SCI-induced hyperalgesia. In contrast, intrathecal application of CGS21680, a selective adenosine A2a receptor agonist, did not inhibit SCI-induced hyperalgesia.


CONCLUSIONS
These results suggest that adenosine inhibits hyperalgesia through the stimulation of A1 receptors. Adenosine or adenosine A1 receptor agonists should be considered as candidates for new therapeutic methods for treating post-SCI dysesthesia.
Horiuchi
H
H
Department of Orthopaedic Surgery, Ehime University School of Medicine, Tohon city, Ehime, Japan.
Ogata
T
T
Morino
T
T
Yamamoto
H
H
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology*; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013117:Spinal Cord Compression / Q000150:complications*; D016896:Treatment Outcome; D014970:Xanthines / Q000494:pharmacology
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D000700:Analgesics; D010627:Phenethylamines; D043682:Receptor, Adenosine A1; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C047235:N-(1-methyl-2-phenylethyl)adenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine