Clonidine-induced neuronal activation in the spinal cord is altered after peripheral nerve injury.
BACKGROUND
Alpha 2 adrenoceptor agonists produce antinociception in normal animals and alleviate mechanical allodynia in animals with nerve injury, although their mechanism of action may differ in these situations. The purpose of this study was to examine the location and number of cells in the spinal cord activated by intrathecal clonidine in these two circumstances and to test whether one class of interneurons, cholinergic, express alpha 2 adrenoceptors.


METHODS
Intrathecal saline or clonidine, 10 and 30 microg, was injected in normal rats or those with mechanical allodynia following partial sciatic nerve section. Two hours later, animals were anesthetized and pericardially perfused. The number of cells in superficial and deep dorsal horn laminae at the L4-L5 level immunostained for phosphorylated cAMP response element binding protein (pCREB) were quantified. In separate studies, the authors colocalized alpha2C adrenoceptors with cholinergic neurons.


RESULTS
Intrathecal clonidine increased pCREB immunoreactive cells in both superficial and deep laminae by 50-100% in normal animals. The number of pCREB immunoreactive cells increased in nerve-injured compared to normal rats. Intrathecal clonidine decreased pCREB immunoreactive cells in the deep dorsal horn of injured animals. Alpha2C adrenoceptors colocalized with cholinergic neurons in both superficial and deep dorsal horn.


CONCLUSIONS
Previous studies suggest a shift in alpha 2 adrenoceptor subtype and the involvement of cholinergic interneurons in antinociception in the spinal cord after nerve injury. The current results suggest that intrathecal clonidine, by direct or indirect methods, increases neuronal activation in normal animals, presumably leading to net inhibition of pain signaling, whereas it reduces the increase in neuronal activity induced by nerve injury.
Pancaro
Carlo
C
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Ma
Weiya
W
Vincler
Michelle
M
Duflo
Frederic
F
Eisenach
James C
JC
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000032:analysis; D003000:Clonidine / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000032:analysis; D012584:Sciatic Nerve / Q000293:injuries*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission
D000700:Analgesics; D017362:Cyclic AMP Response Element-Binding Protein; D018341:Receptors, Adrenergic, alpha-2; D002795:Choline O-Acetyltransferase; D003000:Clonidine