Nefopam has a pharmacologic profile distinct from that of
opioids or other anti-inflammatory drugs. Several recent studies demonstrate that
nefopam has a mechanism of action similar to those of anti-depressants and
anticonvulsants for treating
neuropathic pain. The present study investigates the mechanical antiallodynic effect of
nefopam using immunohistochemical study and western blot analysis in a rat
neuropathic pain model. Twenty-eight male Sprague-Dawley rats were subjected to left fifth lumbar (L5) spinal nerve
ligation and intrathecal
catheter implantation, procedures which were not performed on the 7 male Sprague-Dawley rats in the
sham surgery group (group S).
Nefopam, either 10 or 100 µg/kg (group N10 or N100, respectively), and
normal saline (group C) were intrathecally administered into the
catheter every day for 14 days. The mechanical allodynic threshold of intrathecal
nefopam was measured using a dynamic plantar aesthesiometer. Immunohistochemistry targeting cluster of differentiation molecule 11b (CD11b) and
glial fibrillary acidic protein (GFAP) was performed on the harvested spinal cord at the level of L5.
Extracellular signal-regulated kinase 1/2 (ERK 1/2) and cyclic
adenosine monophosphate response element
binding protein (CREB) were measured using western blot analysis. The N10 and N100 groups showed improved mechanical allodynic threshold, reduced CD11b and GFAP expression, and attenuated ERK 1/2 and CREB in the affected L5 spinal cord. In conclusion, intrathecal
nefopam reduced
mechanical allodynia in a rat
neuropathic pain model. Its mechanical antiallodynic effect is associated with inhibition of glial activation and suppression of the
transcription factors'
mitogen-activated protein kinases in the spinal cord.