prostaglandin-d2 and Headache

Clinical trials use placebos with the assumption that they are inert, thus all placebos are considered to be equal. Here we show that this assumption is wrong and that different placebo procedures are associated to different therapeutic rituals which, in turn, trigger different mechanisms and produce different therapeutic outcomes. We studied high altitude, or hypobaric hypoxia, headache, in which two different placebos were administered. The first was placebo oxygen inhaled through a mask, whereas the second was placebo aspirin swallowed with a pill. Both placebos were given after a conditioning procedure, whereby either real oxygen or real aspirin was administered for three consecutive sessions to reduce headache pain. We found that after real oxygen conditioning, placebo oxygen induced pain relief along with a reduction in ventilation, blood alkalosis and salivary prostaglandin (PG)E2, yet without any increase in blood oxygen saturation (SO2). By contrast, after real aspirin conditioning, placebo aspirin induced pain relief through the inhibition of all the products of cyclooxygenase, that is, PGD2, PGE2, PGF2, PGI2, thromboxane (TX)A2, without affecting ventilation and blood alkalosis. Therefore, two different placebos, associated to two different therapeutic rituals, used two different pathways to reduce headache pain. The analgesic effect following placebo oxygen was superior to placebo aspirin. These findings show that different placebos may use different mechanisms to reduce high altitude headache, depending on the therapeutic ritual and the route of administration. In clinical trials, placebos and outcome measures should be selected very carefully in order not to incur in wrong interpretations.

Topics: Adult; Dinoprost; Dinoprostone; Epoprostenol; Female; Headache; Humans; Hypoxia; Male; Oxygen; Prostaglandin D2; Thromboxane A2

Prostaglandins (PGs) are involved in nociception and mast cell degranulation. Prostaglandin D₂ (PGD₂) is a vasodilatator released during mast cell degranulation. The headache-eliciting effect of PGD₂ has not been studied in man.. Twelve healthy volunteers were randomly allocated to receive intravenous infusion of 384 ng/kg/min PGD₂ over 25 min in a placebo-controlled, double-blind cross-over study. We recorded headache intensity and associated symptoms, velocity in the middle cerebral artery (V(MCA)) and diameter of the superficial temporal artery (STA) and radial artery (RA) using ultrasonography.. In the period 0-14 h, 11 subjects reported headache on PGD₂ compared to one subject on placebo (P = 0.002). During the in-hospital phase (0-120 min), the area under the headache curve was larger on PGD₂ compared to placebo (P < 0.05). Median peak headache, 1 (0-1), occurred 10 min after start of PGD(2) infusion. There was no difference in incidence of headache in the post-hospital phase between PGD₂ (n = 3) and placebo (n = 1). There was a decrease in V(MCA) (P < 0.001), increase in STA (P < 0.001) and RA (P < 0.006) diameter during PGD₂ infusion compared to placebo. Peak decrease in V(MCA) was 28.3% after 10 min and peak increase in STA was 55.7% after 20 min on the PGD₂ day.. The present study shows that PGD₂ is a very strong vasodilator of MCA, STA and RA, but causes only mild headache.

Topics: Adolescent; Adult; Cerebrovascular Circulation; Double-Blind Method; Female; Headache; Humans; Male; Middle Cerebral Artery; Prostaglandin D2; Vasodilation; Young Adult