Co-localization of
opioid and
melanocortin receptor expression, especially at the spinal cord level in the dorsal horn and in the gray matter surrounding the central canal led to the suggestion that
melanocortins might play a role in nociceptive processes. In the present studies, we aimed to determine the effects of
melanocortins, administered intrathecally, on
allodynia, and to ascertain whether there is an interaction between
opioid and
melanocortin systems at the spinal cord level.
Neuropathic pain was induced by chronic constriction injury (CCI) of the right sciatic nerve in rats.
Tactile allodynia was assessed using von Frey filaments, while thermal hyperlagesia was evaluated in cold water
allodynia test. In the present experiments,
melanocortin receptor antagonist,
SHU9119 was much more potent than
mu-opioid receptor agonist,
morphine after their intrathecal (i.th.) administration in neuropathic rats.
SHU9119 alleviated
allodynia in a comparable manner to
DAMGO, a selective and potent
mu-opioid receptor agonist. Administration of
melanocortin receptor agonist,
melanotan-II (MTII) increased the sensitivity to tactile and cold stimulation. Moreover, we demonstrated that the selective blockade of
mu-opioid receptor by
cyprodime (CP) enhanced antiallodynic effect of
SHU9119 as well as pronociceptive action of MTII, whereas the combined administration of
mu receptor agonist (
DAMGO) and
SHU9119 significantly reduced the
analgesic effect of those
ligands.
DAMGO also reversed the proallodynic effect of
melanocortin receptor agonist, MTII. In conclusion, it seems that the endogenous opioidergic system acts as a functional antagonist of melanocortinergic system, and
mu-opioid receptor activity appears to be involved in the modulation of
melanocortin system function.