Intrathecal GM1 ganglioside and local nerve anesthesia reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy.
Our previous experiments demonstrated that systemic treatment with GM1 ganglioside reduces nociceptive behaviors and spinal cord metabolic activity in a rat model of painful peripheral mononeuropathy produced by experimental sciatic nerve ligation (chronic constrictive injury, CCI). In the present study, we examined the effects of intrathecal (i.t.) GM1 treatment on thermal hyperalgesia and spontaneous pain behaviors resulting from nerve ligation in order to determine the locus of GM1 action. In addition, a local anesthetic agent, bupivacaine, given alone or combined with i.t. GM1, was applied to the injured sciatic nerve to determine if peripheral nerve anesthesia would influence post-injury nociceptive behaviors. Thermal hyperalgesia to radiant heat decreased in a dose-dependent manner when GM1 (10-80 nmol, i.t.) was administered once daily onto the lumbar segments of the spinal cord beginning 1 h after experimental nerve injury and continued for the first 9 days after nerve ligation. Moreover, this GM1 (80 nmol) treatment regimen reliably lowered spontaneous pain behavior rating scores in CCI rats suggesting the possible attenuation of spontaneous pain. The central site of i.t. GM1 action is located at the caudal (probably lumbar) spinal cord, since i.t. injection of 20 nmol GM1 onto the cervical spinal cord did not produce any protective effect. A single perinerve injection of a local anesthetic agent, bupivacaine (0.5%, 0.6 ml), on the 3rd day after nerve ligation reduced thermal hyperalgesia for at least 24 h following injection, a duration longer than that of the local anesthetic action of bupivacaine. Neither a single bupivacaine injection nor four daily i.t.(ABSTRACT TRUNCATED AT 250 WORDS)
Mao
J
J
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Price
D D
DD
Hayes
R L
RL
Lu
J
J
Mayer
D J
DJ
D000772:Anesthesia, Local; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002045:Bupivacaine / Q000627:therapeutic use; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000627:therapeutic use*; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000523:psychology; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000293:injuries* / Q000473:pathology
D005677:G(M1) Ganglioside; D002045:Bupivacaine