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Modulation of nociceptive dural input to the trigeminal nucleus caudalis via activation of the orexin 1 receptor in the rat
Author(s) -
Holland P. R.,
Akerman S.,
Goadsby P. J.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.05168.x
Subject(s) - orexin , nociception , stimulation , orexin a , medicine , endocrinology , lateral hypothalamus , antagonist , neuropeptide , chemistry , orexin receptor , receptor antagonist , hypothalamus , receptor
Migraine pathophysiology is thought to involve the trigeminal innervation of the dura mater and intracranial blood vessels. Electrical stimulation of dural blood vessels is painful in humans and causes activation of neurons in the caudal‐most portion of the trigeminal nucleus in experimental animals. The hypothalamic neuropeptides orexin A and B are selectively synthesized in the lateral and posterior hypothalamus, and recent findings have implicated their involvement in nociceptive processing. To evaluate the potential for orexin receptor modulation of trigeminovascular nociceptive afferents, we examined the effects of intravenous orexin A and B on responses of neurons in the trigeminal nucleus caudalis. To dissect the receptor pharmacology of responses to stimulation we utilized the novel orexin 1 receptor (OX 1 R) antagonist N‐(2‐methyl‐6‐benzoxazolyl)‐N′′‐1,5‐naphthyridin‐4‐yl urea (SB‐334867). Orexin A 30 µg/kg ( F 1.9 , 9.8 = 21.93, P < 0.001) and 50 µg/kg ( F 3.2 , 16.4 = 3.28, P < 0.045) inhibited the A‐fibre responses to dural electrical stimulation over 60 min. Maximum inhibition was achieved at 25 min for both 30 µg/kg ( t 5 = 19.83, n = 6, P < 0.001) and 50 µg/kg ( t 5 = 7.74, n = 6, P < 0.001). The response with orexin A 30 µg/kg was reversed by pretreatment with the OX 1 R antagonist SB‐334867 ( F 3.5 , 17.5 = 0.49, P = 0.73), which had no effect when given alone. Orexin B and control vehicle administration had no significant effect on trigeminal neuronal firing. The current study demonstrates that orexin A is able to inhibit A‐fibre responses to dural electrical stimulation via activation of the OX 1 R.