Adenosine A1 and A2 receptors are widely distributed in the brain and spinal cord and
represent a non-opiate target for pain management. Activated spinal A1 receptors inhibit
sensory transmission by inhibiting the slow ventral root potential, which is the
C-fiber-evoked excitatory response associated with nociception. Adenosine may inhibit
intrinsic neurons through an increase in K+ conductance and presynaptic inhibition of sensory
nerve terminals to inhibit the release of substance P and perhaps glutamate. Although
adenosine A3 receptors are not found in the nervous system, adenosine is also known to have
anti-inflammatory properties that may contribute to pain relief in the peripheral setting of
inflammation.