Different analgesic effects of adenosine between postoperative and neuropathic pain

BACKGROUND Adenosine is an endogenous neuromodulator in both the peripheral and central nervous systems. Adenosine inhibits pain signals by hyperpolarizing neuronal membrane. METHODS To clarify the effects of adenosine on pain signals, we tested intrathecal adenosine injection in two neuropathic pains (spinal cord compression and chronic constriction of sciatic nerve) and postoperative pain (plantar incision). RESULTS In all three kinds of pain models, significant shortening of withdrawal latencies to thermal stimulation were detected from 24 h to 1 week after the surgery. Significant improvements of pain sensation were observed in all three models after intrathecal injection of Cl-adenosine 24 h after surgery. At 72 h after surgery, intrathecal Cl-adenosine injection inhibited hyperalgesia in the two neuropathic pain models but not in the postoperative pain model. Adenosine A1R messenger RNA (mRNA) expression significantly decreased in the plantar incision model. Adenosine A1R protein levels also decreased compared with the other two models and normal control. CONCLUSIONS These results suggest that adenosine effectively inhibits pain signals in neuropathic pain but is less effective in postoperative pain because of the decrease in adenosine A1 receptors.