Sensitization of central trigeminovascular neurons: Blockade by intravenous naproxen infusion

Abstract

We have previously observed that migraine attacks impervious to triptan therapy were readily terminated by subsequent intravenous administration of the non-steroidal anti-inflammatory drug (NSAID) ketorolac. Since such attacks were associated with periorbital allodynia -a symptom of central sensitization -we examined whether infusion of the NSAID naproxen can block sensitization of central trigeminovascular neurons in the medullary dorsal horn, using in vivo single-unit recording in the rat. Topical exposure of the cerebral dura to inflammatory soup (IS) for 5 min resulted in a short-term burst of activity (<8 min) and a long-lasting (>120 min) neuronal hyper-responsiveness to stimulation of the dura and periorbital skin (group 1). Infusion of naproxen (1 mg/kg) 2 h after IS (group 1) brought all measures of neuronal responsiveness back to the baseline values recorded prior to IS, and depressed ongoing spontaneous activity well below baseline. When given preemptively 1 h before IS (group 2), naproxen blocked the short-term burst of activity and every long-term measure of neuronal hyper-responsiveness that was studied in the central neurons. The same preemptive treatment, however, failed to block IS-induced short-term burst of activity in C-unit meningeal nociceptors (group 3). The results suggest that parenteral administration of naproxen, unlike triptan therapy, can exert direct inhibition over central trigeminovascular neurons in the dorsal horn. Though impractical as a routine migraine therapy, parenteral NSAID administration should be useful as a non-narcotic rescue therapy for migraine in the setting of the emergency department.

Nitroglycerin provocation in normal subjects is not a useful human migraine model?

“…Highly soluble aspirin 1000 mg is effective in migraine (8) but its mode of action in migraine is uncertain. Animal studies indicate that NSAIDs, including aspirin, may inhibit central trigeminal neurons in nucleus caudalis (9,10). This mechanism of action should work for all kinds of pain in the head, but aspirin was without any effect in the present vascular headache model.…”

Acute Migraine Medications and Evolution From Episodic to Chronic Migraine: A Longitudinal Population‐Based Study

“…It has been suggested that individuals with central sensitization respond poorly to tritpans but not to NSAIDs. 33,34 Perhaps drugs that directly address migraine-related inflammation may prevent or reverse central sensitization and the risk of TM. In individuals with high frequency of attacks, central sensitization is frequently present even between the attacks 17 and, accordingly, the NSAIDs would not be protective.…”

Vagal afferent modulation of spinal trigeminal neuronal responses to dural electrical stimulation in rats

“…Previously it has been shown that some antimigraine drugs of different pharmacological classes, such as triptans (Goadsby and Knight, 1997), non-steroidal anti-inflammatory drugs (Jakubowski et al, 2005(Jakubowski et al, , 2007Sokolov et al, 2010), and calcitonin gene-related peptide receptor antagonists (Storer et al, 2004a) produce considerable inhibition of spike activity of the spinal trigeminal neurons, indicating a key aspect of their pharmacodynamics. In the present study, the use of non-pharmacological but clinically proven effective physiotherapeutic technique resulted in analogous changes in trigeminal neuronal activity.…”