Increased nociceptive response in mice lacking the adenosine A1 receptor

The role of the adenosine A, receptor in nociception was assessed using mice lacking the A, receptor (A(1)R-/-) and in rats. Under normal conditions, the A(1)R-/- mice exhibited moderate heat hyperglesia in comparison to the wild-type mice (A(1)R+/+). The mechanical and cold sensitivity were unchanged. The antinociceptive effect of morphine given intrathecally (i.t.), but not systemically, was reduced in A(1)R-/- mice and this reduction in the spinal effect of morphine was not associated with a decrease in binding of the p-opioid ligand DAMGO in the spinal cord. A(1)R-/- mice also exhibited hypersensitivity to heat, but not mechanical stimuli, after localized inflammation induced by carrageenan. In mice with photochemically induced partial sciatic nerve injury, the neuropathic pain-like behavioral response to heat or cold stimulation were significantly increased in the A(1)R-/-mice. Peripheral nerve injury did not change the level of adenosine A, receptor in the dorsal spinal cord in rats and i.t. administration of R-PIA effectively alleviated pain-like behaviors after partial nerve injury in rats and in C57/BL/6 mice. Taken together, these data suggest that the adenosine A(1) receptor plays a physiological role in inhibiting nociceptive input at the spinal level in mice. The C-fiber input mediating noxious heat is inhibited more than other inputs. A(1) receptors also contribute to the antinociceptive effect of spinal morphine. Selective A(1) receptor agonists may be tested clinically as analgesics, particularly under conditions of neuropathic pain. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.