Effect of IL-1beta microinjection into the posterior hypothalamic area on trigeminal nociception in the rat

The hypothalamus has been implicated in the pathophysiology of the most disabling forms of primary headache, namely migraine and cluster headache. Interleukin-1beta (IL-1beta) is highly expressed in the hypothalamus. We recorded from the trigeminal nucleus caudalis of rats using extracellular electrophysiological methods from neurons responding to electrical stimulation of the peri-middle meningeal artery dura mater and having receptive fields in the ophthalmic division of the trigeminal nerve. Data were collected from fifteen clusters of wide-dynamic range neurons with stable baseline firing responses between 97 and 101% ( n=3 for each unit) to stimulation. Microinjection of IL-1beta into the posterior hypothalamus of 9 animals resulted in a modest inhibition of evoked trigeminal responses in three units, no effect in six and no overall effect for the entire cohort studied. The mean maximum response was a non-significant reduction in firing to 83+/-7% ( n=9) at 30 minutes post-injection of IL-1beta. There was some variation of effect dependent on site of injection with central posterior hypothalamus being the predominant area that resulted in inhibition. There was no inhibition in the six animals injected with vehicle (saline). If there is an important effect for IL-1beta in the posterior hypothalamus it is likely to be highly somatotopically restricted.