Neuropathic pain: A comparison of the glutamate release inhibition and anti-allo

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J Neurochem. 2007 Jan 4

A comparison of the glutamate release inhibition and anti-allodynic

effects of gabapentin, lamotrigine, and riluzole in a model of

neuropathic pain.

Coderre TJ, Kumar N, Lefebvre CD, Yu JS.

Departments of Anesthesia, Neurology & Neurosurgery and Psychology,

McGill University, Montreal, Canada.

The effects of treatment with the anti-convulsant agents,

lamotrigine and riluzole were compared with gabapentin in a rat

experimental model of neuropathic pain. Rats were treated

intraperitoneally, with gabapentin (30, 100 and 300 mg/kg),

lamotrigine (2, 10 and 50 mg/kg) or riluzole (6 and 12 mg/kg) prior

to, and every 12 h for 4 days following chronic constriction injury

(CCI) of the sciatic nerve.

Mechanical and cold sensitivity were assessed prior to surgery

(baseline) and then at 4, 8 and 12 days following CCI. The four-day

treatment with each of the agents was effective at producing

reductions in the development of mechanical and cold

hypersensitivity for periods ranging from the fourth to 12th day.

The highest doses of each of the agents were also assessed on

formalin-induced nociceptive behaviors and on formalin-induced

increases in extracellular glutamate (Glu) and aspartate (Asp) in

the spinal cord dorsal horn (SCDH) of awake behaving rats using in

vivo microdialysis. Nociceptive scores in formalin test were

significantly decreased by gabapentin (300 mg/kg i.p.) and riluzole

(12 mg/kg i.p.), but not by lamotrigine (50 mg/kg i.p.).

Formalin-induced increases in glutamate levels in SCDH were lowered

significantly, as compared with the controls, with all drugs both in

the first phase and second phases, with the greatest effects for

riluzole and gabapentin. Similar suppressive effects of the drugs

were observed on formalin-induced increases in spinal aspartate,

except that gabapentin and lamotrigine produced effects only during

the second phase. Riluzole produced profound and prolonged

reductions in the spinal levels of glutamate and aspartate both for

basal and formalin-stimulated release.

In conclusion, the results suggest that the anti-convulsant agents

gabapentin, lamotrigine and riluzole may reduce the development of

hyperalgesia in a rat model of neuropathic pain by reducing the

spinal release of glutamate. Riluzole's pronounced suppressive

effects on spinal EAA levels is attributed to its established role

as a glutamate release inhibitor and an enhancer of glutamate

transporter activity.