“Locus coeruleus (LC) nucleus is involved in noradrenergic descending pain modulation.
LC receives dense orexinergic projections from the lateral hypothalamus. Orexin-A and -B are hypothalamic peptides which modulate a variety of brain functions via orexin type-1 (OX1) and orexin type-2 (OX2) receptors.
Previous studies have shown that activation of OX1 receptors induces endocannabinoid synthesis and alters synaptic neurotransmission by retrograde signaling via affecting cannabinoid type-1 (CB1) receptors.
In the present study the interaction of orexin-A and endocannabinoids was examined at the LC level in a rat model of inflammatory pain…
This data show that, activation of OX1 receptors in the LC can induce analgesia and also the blockade of OX1 or CB1 receptors is associated with hyperalgesia during formalin test.
Our findings also suggest that CB1 receptors may modulate the analgesic effect of orexin-A.
These results outline a new mechanism by which orexin-A modulates the nociceptive processing in the LC nucleus.”