Systemic administration of
local anesthetics has been shown to transiently reverse thermal and tactile
hypersensitivity induced by
peripheral nerve injury, effects that have been taken as suggesting direct actions on the peripheral nerves. The present study sought to determine whether a central site of action could contribute to, or account for, the effects of
lidocaine on nerve injury-induced thermal and tactile
hypersensitivity. Systemic
lidocaine and its peripherally restricted analogues,
QX-314 or
QX-222, effectively reversed thermal
hypersensitivity after spinal nerve
ligation injury. Nerve injury-induced tactile
hypersensitivity, however, was reversed by systemic
lidocaine but not
QX-314 or
QX-222. Microinjection of either
lidocaine or
QX-314 into the rostral ventromedial medulla fully reversed spinal nerve
ligation-induced thermal and tactile
hypersensitivity. The data strongly suggest that nerve injury-induced thermal and tactile
hypersensitivity are mediated through different mechanisms. In addition, the present study supports a prominent contribution of the central nervous system in the activity of systemically given
lidocaine against nerve injury-induced tactile and thermal
hypersensitivity. Thus,
lidocaine might reverse tactile
hypersensitivity mainly through its actions within the central nervous system, whereas its reversal of thermal
hypersensitivity might occur through either central or peripheral sites.
PERSPECTIVE: Nerve injury-induced
neuropathic pain has proved remarkably difficult to treat. Systemic administration of
ion channel blockers such as
lidocaine has been explored for the management of chronic
pain. This work indicates that systemic rather than local administration of
lidocaine would be more effective in treating
tactile allodynia.