Inhibition of nociceptive dural input in the trigeminal nucleus caudalis by somatostatin receptor blockade in the posterior hypothalamus.
Somatostatin is a neuromodulator in the central nervous system and is involved in the regulation of metabolic and neuroendocrine functions. Recent experimental and clinical findings point to a role for somatostatin in the central processing of nociception. We studied the effects of somatostatin receptor modulation in the posterior hypothalamic area (PH) of the rat on dural nociceptive input. Somatostatin (10 microg/microl) and the somatostatin antagonist cyclo-somatostatin (50 microg/microl) were microinjected into the PH and the effects on responses of neurons in the trigeminal subnucleus caudalis studied. Injection of somatostatin (n=11) did not affect A- and C-fibre responses to dural electrical stimulation, nor was spontaneous activity altered (P>0.05). Injection of cyclo-somatostatin (n=10) into the PH reduced A-(-35.5+/-5.8%) and C-fibre (-43.1+/-7.5%) responses to dural stimulation and resulted in decreased spontaneous activity (-38.1+/-7.3%, P<0.05). Responses to facial thermal stimulation were decreased by 51.2+/-5.8% (n=5). Control injections had no significant effect (n=9). Blockade of somatostatin receptors in the PH has an anti-nociceptive effect on dural and facial input, probably mediated via GABAergic mechanisms. As somatostatin is also involved in hypothalamic regulation of metabolic, neuroendocrine and autonomic functions, somatostatin receptor mechanisms in the PH may play a role in the pathophysiology of primary headache disorders, such as migraine or cluster headache.
Bartsch
T
T
Headache Group, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Levy
M J
MJ
Knight
Y E
YE
Goadsby
P J
PJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007034:Hypothalamus, Posterior / Q000187:drug effects*; D008297:Male; D008845:Microinjections / Q000379:methods; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology / Q000528:radiation effects; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D012867:Skin / Q000294:innervation; D014275:Trigeminal Caudal Nucleus / Q000166:cytology / Q000187:drug effects*
D018756:GABA Antagonists; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C067675:cyclosomatostatin; D001640:Bicuculline