Nerve growth factor (
NGF) is involved in
pain transduction mechanisms and plays a key role in many persistent
pain states, notably those associated with
inflammation. On this basis, both the
NGF ligand and its
receptor TrkA (
tyrosine kinase A) represent an eligible target for
pain therapy. Although the direct involvement of
NGF in
pain modulation is well established, the effect of a direct functional block of the
TrkA receptor is still unknown. In this study, we have demonstrated that MNAC13, the only anti-TrkA
monoclonal antibody for which function neutralizing properties have been clearly shown both in vitro and in vivo, induces
analgesia in both inflammatory and
neuropathic pain models, with a surprisingly long-lasting effect in the latter. The
formalin-evoked
pain licking responses are significantly reduced by the MNAC13 antibody in CD1 mice. Remarkably, treatment with the anti-TrkA antibody also produces a significant antiallodynic effect on
neuropathic pain: repeated i.p.
injections of MNAC13 induce significant functional recovery in mice subjected to sciatic nerve
ligation, with effects persisting after administration. Furthermore, a clear synergistic effect is observed when MNAC13 is administered in combination with
opioids, at doses that are not efficacious per se. This study represents a direct demonstration that
neutralizing antibodies directed against the
TrkA receptor may display potent
analgesic effects in inflammatory and
chronic pain.