Neuropathic pain is among the most common and difficult-to-treat types of
chronic pain and is associated with
sodium channel malfunction. The
sodium channel blocker ralfinamide has exhibited potent
analgesic effects in several preclinical
pain models and in patients with mixed
neuropathic pain syndromes (Phase II trials), but it failed to ameliorate neuropathic
low back pain in Phase III trials. It is unclear whether
ralfinamide is effective against
neuropathic pain induced by specified etiologies. In the present study, the antinociceptive effects of
ralfinamide in
neuropathic pain models induced by spared nerve injury and
chemotherapy were compared in a
gabapentin-controlled manner. The effects of
ralfinamide on physiological
pain were evaluated in mechanical withdrawal, hot plate, and
acetic acid writhing tests. We also investigated the effects of
ralfinamide on cardiovascular function and locomotor activity. Oral
ralfinamide dose-dependently alleviated spared nerve injury-induced
allodynia in rats and mice.
Ralfinamide increased mechanical withdrawal thresholds in
oxaliplatin-induced and
paclitaxel-induced
neuropathic pain.
Ralfinamide did not affect physiological
pain, locomotion, or cardiovascular function. Together,
ralfinamide attenuated
mechanical allodynia in all the
neuropathic pain models tested, with subtle differences in efficacy. The effect of
ralfinamide is comparable to that of
gabapentin, but with no interference in basal mechanical sensitivity. The present study supports the effectiveness of selective
sodium channel blockade as an
analgesic strategy, as well as the development of compounds similar to
ralfinamide.