Posterior hypothalamic modulation of ocular‐responsive trigeminal subnucleus caudalis neurons is mediated by O rexin‐ A and O rexin1 receptors

Orexin‐A ( O x A ) is synthesized in posterior and lateral regions of the hypothalamus and contributes to homeostatic regulation of body functions including pain modulation. To determine if orexinergic mechanisms contribute to posterior hypothalamus ( PH )‐induced modulation of ocular input to subnucleus caudalis/upper cervical (Vc/C1) neurons, the orexin‐1 receptor antagonist SB 334867 was applied to the dorsal brainstem surface prior to PH disinhibition, by bicuculline methiodide, in male rats under isoflurane anesthesia. Ocular input to V c/ C 1 units by bright light or hypertonic saline was markedly reduced by PH disinhibition and reversed completely by local V c/ C 1 application of SB 334867. O x A applied to the V c/ C 1 surface mimicked the effects of PH disinhibition in a dose‐dependent manner. O x A ‐induced inhibition was prevented by co‐application of SB 334867, but not by the orexin‐2 receptor antagonist TCS Ox2 29. PH disinhibition and local O x A application also reduced the high threshold convergent cutaneous receptive field area of ocular units, suggesting widespread effects on somatic input to V c/ C 1 ocular units. V c/ C 1 application of O x A or SB 334867 alone did not affect the background discharge of ocular units and suggested that the PH – O x A influence on ocular unit activity was not tonically active. V c/ C 1 application of O x A or SB 334867 alone also did not alter mean arterial pressure, whereas PH disinhibition evoked prompt and sustained increases. These results suggest that stimulus‐evoked increases in PH outflow acts through O x A and orexin‐1 receptors to alter the encoding properties of trigeminal brainstem neurons responsive to input from the ocular surface and deep tissues of the eye.