Intrathecal Lamotrigine Attenuates Mechanical Allodynia and Suppresses Microglial and Astrocytic Activation in a Rat Model of Spinal Nerve Ligation

Abstract

PurposeLamotrigine, 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 MethodsFollowing 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).ResultsSpinal-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.ConclusionContinuously 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.

Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord

“…[ 7 , 8 ] The sodium channel blocking effect could have resulted in less intense firing of neurons involved in peripheral nerve injury, and subsequent inhibition of activation of microglia. [ 25 , 26 ] The causal relationship between anti-allodynic effect of i.t. treatment of PA and microglial activation should be further explored to elucidate the mechanism underlying its anti-allodynic effect.…”

ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain

“…These are just a few of the possible microglial biochemical changes induced by nerve-injury that may be involved in generating and maintaining neuropathic pain. Despite the uncertain mechanism by which microglial cells cause neuropathic pain, multiple studies have shown that microglial activation inhibiting decreases hyperalgesia and allodynia following nerve damage [51][52][53].…”