Reduction in the mechanonociceptive response by intrathecal administration of glycine and related compounds.
We have previously reported that enhanced glycine release is produced by epidural spinal cord stimulation, a clinical method for treating neuropathic pain. Our current hypothesis is that glycine administered intrathecally reduces neuropathic pain as measured by the Randall-Selitto method. Neuropathic rats created by unilateral partial ligation of the sciatic nerve were treated with intrathecal infusion of glycine, strychnine, MK-801, or 5,7-DKA at 0.1 mumol, or artificial CSF for 2 hours at a rate of 10 microliters/min. Force required to produce the pain response was significantly increased after glycine administration and reduced using strychnine, a specific glycine receptor (Gly l) antagonist. Strychnine blocked the response to glycine when infused together. Administration of the non-specific NMDA receptor MK-801 antagonist and 5,7-DKA, a specific glycine-NMDA receptor (Gly 2) antagonist, however, failed to block the response to glycine. Our results provide evidence for the use of glycine and related compounds to treat neuropathic pain.
Simpson
R K
RK
Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Gondo
M
M
Robertson
C S
CS
Goodman
J C
JC
D000818:Animals; D002555:Cerebrospinal Fluid / Q000502:physiology; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005998:Glycine / Q000627:therapeutic use*; D018684:Glycine Agents / Q000627:therapeutic use; D007278:Injections, Spinal; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects*; D009437:Neuralgia / Q000188:drug therapy*; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology*; D013331:Strychnine / Q000627:therapeutic use; D004561:Transcutaneous Electric Nerve Stimulation
D018691:Excitatory Amino Acid Antagonists; D018684:Glycine Agents; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid; D013331:Strychnine; C066192:5,7-dichlorokynurenic acid; D005998:Glycine