Intrathecal adenosine following spinal nerve ligation in rat: short residence time in cerebrospinal fluid and no change in A(1) receptor binding.
BACKGROUND
Intrathecal adenosine produces a remarkably prolonged effect to relieve mechanical hypersensitivity after peripheral nerve injury in animals. The purpose of the current study was to investigate whether this reflected an alteration in kinetics of adenosine in cerebrospinal fluid or in the number of spinal A1 adenosine receptors after nerve injury.


METHODS
Male rats were anesthetized, and the left L5 and L6 spinal nerves were ligated. Two weeks later, a lumbar intrathecal catheter and intrathecal space microdialysis catheter were inserted. Adenosine, 20 microg, was injected intrathecally in these and in normal rats, and microdialysates of the intrathecal space were obtained. Radioligand binding studies of adenosine A1 receptors were determined in spinal cord tissue from other normal and spinal nerve-ligated rats.


RESULTS
Adenosine disappeared from rat cerebrospinal fluid within 30 min after intrathecal injection, with no difference between normal and spinal nerve-ligated animals. A1 adenosine receptor binding sites in the spinal cord were increased after spinal nerve ligation. This increase disappeared when adenosine deaminase was added to the membrane homogenates, suggestive of decreased endogenous adenosine in the membranes of nerve-ligated animals.


CONCLUSIONS
These data show that prolonged alleviation of hypersensitivity observed with intrathecal adenosine in this animal model of neuropathic pain is not due to prolonged residence in cerebrospinal fluid, although pharmacokinetics in tissues are unknown. Similarly, there is no evidence for up-regulation in spinal A1 adenosine receptors after spinal nerve ligation, and the adenosine deaminase experiment is consistent with a depletion of adenosine in spinal cord tissue after spinal nerve ligation.
Bantel
Carsten
C
Department of Anesthesiology, Wake Forst University Schhol of Medicine, Winston-Salem, North Carolina 27157, USA.
Tobin
Joseph R
JR
Li
Xinhui
X
Childers
Steven R
SR
Chen
Shao Rui
SR
Eisenach
James C
JC
D000241:Adenosine / Q000134:cerebrospinal fluid / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D007278:Injections, Spinal; D008026:Ligation; D008297:Male; D017551:Microdialysis; D010146:Pain / Q000188:drug therapy*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000378:metabolism; D013127:Spinal Nerves / Q000502:physiology; D014970:Xanthines / Q000378:metabolism
D000700:Analgesics; D018047:Receptors, Purinergic P1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine