Spinal cord alpha 2-adrenoceptors may be located postsynaptically with respect to primary sensory neurons: destruction of primary C-afferents with neonatal capsaicin does not affect the number of [3H]clonidine binding sites in mice.

Mice were treated with 50 mg/kg capsaicin on the second day of life, which causes a permanent and selective loss of a large proportion of afferent C-fibers. Two months later the spinal cords were removed and the content of alpha 2-adrenoceptors assayed by radioligand binding with [3H]clonidine. In these tests the content of alpha 2-adrenoceptors was found to be 568 +/- 27 fmol/mg protein in the capsaicin-treated animals and it was virtually the same -596 +/- 9 fmol/mg protein - in control animals. The affinity of [3H]clonidine for the alpha 2-adrenoceptor was not affected by capsaicin (Kd = 3.25 +/- 0.29 nM for capsaicin and 3.23 +/- 0.32 nM for the controls). In functional tests clonidine applied s.c. induced a marked reduction in the pain sensitivity to capsaicin. The results indicate that spinal cord alpha 2-adrenoceptors are located postsynaptically with respect to the primary sensory neurons and potentially that stimulation of these receptors by alpha 2-adrenoceptor agonist mediates inhibition of nociceptive transmission.