Intrathecal Lamotrigine Attenuates Mechanical Allodynia and Suppresses Microglial and Astrocytic Activation in a Rat Model of Spinal Nerve Ligation.
10.3349/ymj.2013.54.2.321
- Author:
Yun Sik CHOI
1
;
In Gu JUN
;
Sung Hoon KIM
;
Jong Yeon PARK
Author Information
1. Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. jongyeon_park@amc.seoul.kr
- Publication Type:Original Article
- Keywords:
Astrocytes;
intrathecal;
lamotrigine;
microglia;
neuropathic pain
- MeSH:
Animals;
Astrocytes/drug effects/*physiology;
Disease Models, Animal;
Hyperalgesia/*drug therapy;
Infusions, Spinal;
Ligation;
Male;
Microglia/drug effects/*physiology;
Neuralgia/drug therapy;
Rats;
Rats, Sprague-Dawley;
Spinal Nerves/*injuries;
Triazines/administration & dosage/*therapeutic use;
Voltage-Gated Sodium Channel Blockers/administration & dosage/*therapeutic use
- From:Yonsei Medical Journal
2013;54(2):321-329
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: 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. MATERIALS AND METHODS: Following left L5/6 spinal nerve ligation (SNL), Sprague-Dawley male rats were intrathecally administered lamotrigine (24, 72, or 240 microg/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 microg/day) prevented the development of mechanical allodynia, and lower dose of lamotrigine (72 microg/day) ameliorated allodynia. Intrathecal lamotrigine (72 and 240 microg/day) inhibited nerve ligation-induced microglial and astrocytic activation, as evidenced by reduced numbers of cells positive for OX-42 and GFAP. CONCLUSION: 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.
