Adenosine A1but Not A2aReceptor Agonist Reduces Hyperalgesia Caused by a Surgical Incision in Rats

Abstract

ADENOSINE, an important endogenous modulator of neurotransmission, inhibits synaptic transmission in the central nervous system1–3 and is involved in the regulation of several biologic functions, including anxiety, cognition, and memory, mediating its actions by stimulation of adenosine A¹, A^2a, A^2b, and A³G protein–coupled receptors. There is now ample evidence that activation of spinal A¹adenosine receptors (A¹Rs), present in superficial layers of the dorsal spinal cord and on afferent terminals of nociceptors,4 causes antinociception after nerve injury or inflammation and decreases C fiber–driven responses in dorsal horn neurons.5 Mice lacking A¹Rs exhibited increased nociceptive responses.6,7 However, the exact mechanisms by which A¹Rs agonists cause antinociception remain to be defined. Patel et al. 8 demonstrated that activation of A¹Rs hyperpolarizes spinal dorsal horn neurons by increasing potassium conductance, resulting in postsynaptic inhibition of excitatory transmission. Furthermore, the inhibitory action of adenosine in the spinal cord may be caused by activation of presynaptic A¹Rs present on sensory afferent terminals and dorsal root ganglion neurons, leading to a decrease in cyclic adenosine monophosphate (cAMP) production and an inhibition of excitatory neurotransmitter release.1,2