Galanin and galanin receptors (GalRs) have been reported to be
involved in the transmission and modulation of nociceptive
information in the central nervous system (CNS). However, the
underlying mechanism of the antinociception of GalRs in
neuropathic pain remains unclear. This study investigated the
antinociception induced by galanin receptor 1 (GalR1) via protein
kinase A (PKA) signaling pathway in the nucleus accumbens
(NAc) of rats with neuropathic pain. A mononeuropathy model
was replicated by ligation of the left sciatic nerve, following which
the expression of phospho-PKA (p-PKA) in the NAc were
markedly up-regulated at 14th and 28th day after ligation of sciatic
nerve, and p-PKA expression was down-regulated by intra-NAc
injection of GalR1 agonist M617, but the GalR1 antagonist M35
did not have an effect. We also found that M35 in the NAc
blocked the M617-induced increase in the hind paw withdrawal
latencies (HWLs) of rats with mononeuropathy, but M35 alone
had no effect on HWLs, and PKA inhibitor H-89 attenuated the
M617-induced an increase in the HWLs. These results suggested
that GalR1 induced an antinociception via inhibiting PKA
activation, implying that GalR agonists may be potential and
potent therapeutic options to treat chronic neuropathic pain.