Intrathecal morphine reduces allodynia after peripheral nerve injury in rats via activation of a spinal A1 adenosine receptor.
BACKGROUND
The degree to which intrathecally administered morphine can alleviate hypersensitivity in animals after peripheral nerve injury is controversial, and the mechanisms by which morphine works in these circumstances are uncertain. In normal animals, morphine induces adenosine release, and in vitro data suggest that this link is disrupted after peripheral nerve injury. Therefore, using a controlled, blinded study design, the authors tested intrathecal morphine efficacy in rats with peripheral nerve injury and the role of spinal A1 adenosine receptors in the action of morphine.


METHODS
Male rats underwent intrathecal catheter implantation and lumbar spinal nerve ligation, resulting in hypersensitivity to tactile stimulation of the paw. Intrathecal morphine alone or with naloxone or the specific A1 adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentyxanthine (DPCPX), was administered, and withdrawal threshold to von Frey filament application to the hind paw was determined.


RESULTS
Intrathecal morphine (0.25-30 microg) dose-dependently reversed mechanical hypersensitivity after spinal nerve ligation, with an ED50 of 0.79 microg. The effect of morphine was blocked by intrathecal naloxone. Intrathecal DPCPX alone had no effect on withdrawal threshold after spinal nerve ligation but completely reversed the effect of morphine, with an ID50 of 5.6 microg.


CONCLUSIONS
This study is in accord with two recent reports that support short-term efficacy of intrathecal morphine to reverse hypersensitivity to mechanical stimuli in animal models of neuropathic pain. Despite previous studies demonstrating that morphine releases less adenosine after peripheral nerve injury, the current study suggests that the antihypersensitivity effect of morphine in these conditions is totally reliant on A1 adenosine receptor activation.
Zhang
Yong
Y
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Conklin
Dawn R
DR
Li
Xinhui
X
Eisenach
James C
JC
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism* / Q000502:physiology; D013127:Spinal Nerves / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism
D043682:Receptor, Adenosine A1; D009020:Morphine