It has been shown that
kappa opioid receptor (KOR) antagonists, such as
nor-binaltorphimine (
nor-BNI), have antinociceptive effects in some
pain models that affect the trigeminal system. Also, its
anxiolytic-like effect has been extensively demonstrated in the literature. The present study aimed to investigate the systemic, local, and central effect of
nor-BNI on trigeminal
neuropathic pain using the infraorbital nerve constriction model (CCI-ION), as well as to evaluate its effect on anxiety-like behavior associated with this model. Animals received
nor-BNI systemically; in the trigeminal ganglion (TG); in the subarachnoid space to target the spinal trigeminal nucleus caudalis (Sp5C) or in the central amygdala (CeA) 14 days after CCI-ION surgery. Systemic administration of
nor-BNI caused a significant reduction of facial
mechanical hyperalgesia and promoted an
anxiolytic-like effect, which was detected in the elevated plus-maze and the light-dark transition tests. When administered in the TG or CeA, the KOR antagonist was able to reduce facial
mechanical hyperalgesia induced by CCI-ION, but without changing the anxiety-like behavior. Moreover, no change was observed on nociception and anxiety-like behavior after
nor-BNI injection into the Sp5C. The present study demonstrated antinociceptive and
anxiolytic-like effects of
nor-BNI in a model of trigeminal
neuropathic pain. The antinociceptive effect seems to be dissociated from the
anxiolytic-like effect, at both the sites involved and at the dose need to achieve the effect. In conclusion, the kappa
opioid system may represent a promising target to be explored for the control of trigeminal
pain and associated anxiety. However, further studies are necessary to better elucidate its functioning and modulatory role in chronic trigeminal
pain states.