Papers of the Week

Memantine (MEM) is one of the important clinical medications in treating moderate to severe Alzheimer disease. The effect of MEM on preventing or treating punctate allodynia has been thoroughly studied but not on the induction of dynamic allodynia. The aim of this study is to investigate whether MEM could prevent the induction of dynamic allodynia and its underlying spinal mechanisms. 1)in vivo SNI pain model, pretreatment with MEM at a lower dose (10nmol, i.t.; MEM-10) selectively prevented the induction of dynamic allodynia, but not the punctate allodynia. 2) Pretreatment with either MK801-10 (MK801-10nmol, i.t.) or higher dose of MEM (30nmol, i.t.; MEM-30) prevented the induction of both dynamic and punctate allodynia. 3) MEM-10 showed significant effect on the inhibition of the SNI induced overactivation of microglia in spinal dorsal horn. 4) In contrast, in CFA model, MEM-10 neither affected the CFA injection induced activation of microglia in spinal dorsal horn nor the induction of dynamic allodynia. 5) Immunohistology studies showed Kir2.1 channel distributed widely and co-localized with microglia in the spinal dorsal horn of mice. 6) Pretreatment with either minocycline, a microglia inhibitor, or ML133, a Kir2.1 inhibitor, both selectively prevented the overactivation of microglia in spinal dorsal horn, and the induction of dynamic allodynia following SNI. The selectively inhibitory effect on the induction of dynamic allodynia in SNI model by low dose of the memantine (MEM-10) was tightly correlated with the blockade of microglia Kir2.1 channel to suppress the microglia activation.