The involvement of
opioid receptor activation in the antinociceptive effect of either
fluvoxamine, a
selective serotonin reuptake inhibitor, or
serotonin (5-HT) on
thermal hyperalgesia and
mechanical allodynia in a model of
neuropathic pain in mice induced by sciatic nerve
ligation was examined. The experiments were conducted 2 or 6 weeks after unilateral sciatic nerve
ligation. Ipsilateral
thermal hyperalgesia and
mechanical allodynia were observed both 2 and 6 weeks after sciatic nerve
ligation. Neither s.c.
fluvoxamine nor i.t.
5-HT affected sciatic nerve
ligation-induced
thermal hyperalgesia or
mechanical allodynia in mice 2 weeks after sciatic nerve
ligation. However, the same dose of either
fluvoxamine or
5-HT significantly reduced
mechanical allodynia but not
thermal hyperalgesia in sciatic nerve ligated mice 6 weeks after surgery. The antinociceptive effect of
fluvoxamine on sciatic nerve
ligation-induced
mechanical allodynia in mice 6 weeks after surgery was completely abolished by pretreatment with either
naloxone, a nonselective
opioid receptor antagonist, or
beta-funaltrexamine, a selective
mu-opioid receptor antagonist. Furthermore, pretreatment with
naltrindole, a selective
delta-opioid receptor antagonist, partially but significantly inhibited the antinociceptive effect of
fluvoxamine in sciatic nerve ligated mice at the 6th postoperative week. The antinociceptive effect induced by i.t.
5-HT was also completely antagonized by either
naloxone or
beta-funaltrexamine, and partially inhibited by
naltrindole. However, pretreatment with
nor-binaltorphimine, a selective
kappa-opioid receptor antagonist, had no effect against either s.c.
fluvoxamine- or i.t. 5-HT-induced antinociception. These results suggest that the antinociceptive effect of s.c.
fluvoxamine or i.t.
5-HT in the chronic state of sciatic nerve
ligation-induced
neuropathic pain may be related to opioidergic activity, mainly through the activation of spinal mu- and
delta-opioid receptors.