Relief of inflammatory pain in rats by local use of the selective P2X7 ATP receptor inhibitor, oxidized ATP.
OBJECTIVE
Oxidized ATP (oATP) is a selective inhibitor of the P2Z/P2X7 ATP receptor for extracellular ATP, which contributes to the antinociceptive effect. This study sought to determine the mechanism by which local administration of oATP is able to relieve inflammatory pain in arthritic rat paws.


METHODS
Arthritis was induced in Wistar rats by injections of Freund's complete adjuvant into one hind paw. Nociceptive thresholds were measured before and after local injection of oATP into the inflamed paws. The influence on pain transmission due to the presence of recruited inflammatory cells at the site of inflammation was determined by inhibiting the initial phase of their migration (by intravenous treatment with fucoidin, which blocks the adhesion molecules of the selectin family). ATP intraplantar content was determined in the different experimental conditions. Histologic features of the hind paws were evaluated by using the anti-P2X7 receptor polyclonal antibody.


RESULTS
Intraplantar administration of oATP into inflamed paws significantly relieved inflammatory pain. The antinociceptive effect of oATP was independent of the immune-cell recruitment. ATP levels in inflamed tissues were significantly reduced by oATP treatment. A variable presence of P2X7 receptors on cutaneous sensory nerves with respect to the different treatments was observed. Following oATP treatment, there was a reduction in P2X7 expression in the endings of peripheral nerves, as well as in endothelial cells.


CONCLUSIONS
Oxidized ATP inhibits inflammatory pain in arthritic rats by inhibition of the P2X7 receptor for ATP, which is localized on nerve terminals.
Dell'Antonio
Giacomo
G
IRCCS Hospital San Raffaele, Milan, Italy.
Quattrini
Angelo
A
Cin
Elena Dal
ED
Fulgenzi
Alessandro
A
Ferrero
Maria Elena
ME
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*; D000287:Administration, Topical; D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D001168:Arthritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004487:Edema / Q000188:drug therapy; D005528:Foot; D006614:Hindlimb; D007107:Immune System / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D010146:Pain / Q000503:physiopathology*; D010166:Palliative Care; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D058486:Receptors, Purinergic P2X7; D040521:Subcutaneous Tissue / Q000378:metabolism
D000700:Analgesics; C546470:P2rx7 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; C017199:2',3'-dialdehyde ATP; D000255:Adenosine Triphosphate