Melatonin inhibits the up-regulation of N-type calcium channel in
neuropathic pain by activating the MT2 receptor in rats
Abstract
The aim of the study was to clarify the effect of melatonin on
neuropathic pain by N-type calcium channel (Cav2.2) inhibition in dorsal
root ganglion (DRG) neurons after spared nerve injury (SNI) surgery.
Immunofluorescence was used to identify the co-expression of Cav2.2 and
the MT2 receptor and detect the changes in Cav2.2 expression in DRG
neurons. Western-blot was also performed to detect the expression of
Cav2.2 in DRG neurons. The action potential and current of Cav2.2
channels in DRG neurons were detected using whole-cell patch clamp
analysis. Behavioral studies were conducted using thermal stimulation
and acetone after melatonin was injected intraperitoneally. The results
revealed that Cav2.2 and the MT2 receptor were co-expressed in medium
and small sized DRG neurons, and the intensity of Cav2.2 increased after
SNI. Injection of melatonin activated the MT2 receptor and relieved
nociceptive pain through decreased the Cav2.2 expression and current in
DRG neurons. Melatonin can significantly decrease the increase in Cav2.2
current density and excitability after SNI. In addition, the Cav2.2
activation curve shifted to the left after SNI, but there was no change
in inactivation. 10 μM melatonin significantly inhibited the
excitability of DRG neurons and Cav2.2 current, the inactivation curve
of Cav2.2 current shifted significantly to the left. However, the MT2
receptor antagonist 4-P-PDOT reversed the inhibition of melatonin on
Cav2.2 current. We conclude that melatonin inhibits the increased Cav2.2
expression and current; on the other hand, it reduces the excitability
of DRG neurons after SNI surgery via the MT2 receptor pathway.