Intrathecal lamotrigine attenuates mechanical allodynia and suppresses microglial and astrocytic activation in a rat model of spinal nerve ligation.
OBJECTIVE
Lamotrigine, a novel anticonvulsant, is a sodium channel blocker that is efficacious in certain forms of neuropathic pain. Recently, microglial and astrocytic activation has been implicated in the development of nerve injury-induced neuropathic pain. We have assessed the effects of continuous intrathecal administration of lamotrigine on the development of neuropathic pain and glial activation induced by L5/6 spinal-nerve ligation in rats.


METHODS
Following left L5/6 spinal nerve ligation (SNL), Sprague-Dawley male rats were intrathecally administered lamotrigine (24, 72, or 240 μg/day) or saline continuously for 7 days. Mechanical allodynia of the left hind paw to von Frey filament stimuli was determined before surgery (baseline) and once daily for 7 days postoperatively. On day 7, spinal activation of microglia and astrocytes was evaluated immunohistochemically, using antibodies to the microglial marker OX-42 and the astrocyte marker glial fibrillary acidic protein (GFAP).


RESULTS
Spinal-nerve ligation induced mechanical allodynia in saline-treated rats, with OX-42 and GFAP immunoreactivity being significantly increased on the ipsilateral side of the spinal cord. Continuously administered intrathecal lamotrigine (240 μg/day) prevented the development of mechanical allodynia, and lower dose of lamotrigine (72 μg/day) ameliorated allodynia. Intrathecal lamotrigine (72 and 240 μg/day) inhibited nerve ligation-induced microglial and astrocytic activation, as evidenced by reduced numbers of cells positive for OX-42 and GFAP.


CONCLUSIONS
Continuously administered intrathecal lamotrigine blocked the development of mechanical allodynia induced by SNL with suppression of microglial and astrocytic activation. Continuous intrathecal administration of lamotrigine may be a promising therapeutic intervention to prevent neuropathy.
Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea.
Yun-Sik
YS
Choi
In-Gu
IG
Jun
Sung-Hoon
SH
Kim
Jong-Yeon
JY
Park
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy*; D060186:Infusions, Spinal; D000077213:Lamotrigine; D008026:Ligation; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009437:Neuralgia / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000293:injuries*; D014227:Triazines / Q000008:administration & dosage / Q000627:therapeutic use*; D061567:Voltage-Gated Sodium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*
D014227:Triazines; D061567:Voltage-Gated Sodium Channel Blockers; D000077213:Lamotrigine