Fig. 3.
Pharmacological activation of NO/cGMP every other day for 9 days causes chronic hyperalgesia that does not revert to baseline until days 13–15[120]. Thus, days after clearance of exogenous NO/cGMP activators, endogenous NO/cGMP signaling is upregulated and potentiates chronicity. Blocking sGC using ODQ restores baseline response on day 10. This migraine model is responsive to various anti-migraine drugs in human use.