Intrathecal lithium reduces neuropathic pain responses in a rat model of peripheral neuropathy.
We tested the ability of lithium (Li(+)) to block heat hyperalgesia, cold allodynia, mechanical allodynia and mechanical hyperalgesia in rats experimentally subjected to painful peripheral neuropathy. Chronic constrictive injury (CCI) to the sciatic nerve induced persistent hyperalgesia and allodynia. Intrathecal injection of Li(+) (2.5-40 micromol) into the region of lumbar enlargement dose-dependently reduced heat hyperalgesia, cold allodynia and mechanical allodynia for 2-6 h after injection, but had no effect on mechanical hyperalgesia. Li(+) had no significant effect on responses from control and sham-operated animals. Intrathecal injection of myo-inositol (2.5 mg) significantly reversed both the anti-hyperalgesic and anti-allodynic effect of Li(+). These findings suggest that intrathecal Li(+) suppresses neuropathic pain response in CCI rats through the intracellular phosphatidylinositol (PI) second messenger system in spinal cord neurons. Lithium (Li(+)) has already found widespread clinical application; these results suggest that its therapeutic utility may be extended to include treatment of neuropathic pain syndromes resulting from peripheral nerve injury.
Shimizu
T
T
Department of Anesthesiology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, Japan. tshimizu@anes.med.osaka-u.ac.jp
Shibata
M
M
Wakisaka
S
S
Inoue
T
T
Mashimo
T
T
Yoshiya
I
I
D000818:Animals; D002908:Chronic Disease; D003080:Cold Temperature; D004347:Drug Interactions; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology; D007278:Injections, Spinal; D007294:Inositol / Q000494:pharmacology; D008094:Lithium / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D007294:Inositol; D008094:Lithium