The lack of efficacy of oxytocin and NSAIDs

studies [8–10]. The first study found that 32 IU of oxytocin nasal spray induced better results in patients with chronic migraine if they had not taken NSAIDs [8]. However, this study failed to report the number of patients and statistical evaluation. The second study found that 40 IU of oxytocin (twice a day, for 13 weeks) reduced abdominal discomfort but not constipation in 59 women with refractory constipation [9]. However, this study did not report whether NSAIDs were used or not [1, 9]. The third study found that oxytocin dose dependently reduced the severity of headache in 112 patients not taking analgesic medications [10]. However, the doses of oxytocin were not specified. It is reported that patients received six puffs of a solution containing different concentrations of oxytocin (100, 200 or 400 ng) without specifying whether these concentrations were referred to 1 ml, to 1 puff, or to 6 puffs. Considering that usually 1 puff consists of 0.1 ml of solution, and 1 IU corresponds to 2 μg of oxytocin [11], we calculated the maximum dose of oxytocin expressed in IU. If the highest dose (400 ng) was referred to 1 ml, each patient received 0.12 IU (400 ng/ml; each patient received 0.6 ml; 0.6 ml contains 240 ng, corresponding to 0.12 IU); if the dose was referred to 1 puff, each patient received 1.2 IU (400 ng/ puff; 400 ng × 6 = 2,400 ng corresponding to 1.2 IU); if it referred to the total of 6 puffs, each patient received 0.2 IU (400 ng/6 puffs corresponding to 0.2 IU). Accordingly, the maximum dose administered (1.2 IU) would be much lower than those usually administered. For instance, 27 and 33 times lower than that used in the first (32 IU) and in the second study (40 IU), respectively [8, 9]. The limits of these studies did not allow any conclusions to be drawn on the possible influence of NSAIDs on the effects induced by oxytocin. It has been observed that NSAID administration reduces the secretion of endogenous oxytocin [12], although this effect should not influence response We read with interest the Commentary of Drs. Kwong and Chan on the lack of analgesic effects induced by the administration of oxytocin nasal spray to fibromyalgic patients [1–3]. We agree with them that these negative results are very disappointing, particularly as the inverse relationship between plasma oxytocin levels and the severity of pain found by other studies persuaded us to conduct our study [4]. We also agree with them on the possibility that the severity of pain may change throughout the menstrual cycle of fertile women. Indeed, in fibromyalgic patients, the severity of pain is higher in the luteal than in the follicular phase [5], and, in healthy fertile women, plasma oxytocin levels are lower during the luteal than the follicular phase [6]. The expression of brain oxytocin receptors is modulated by estrogen and progesterone [7]. However, in our study, patients included seven postmenopausal and seven premenopausal women, most of the latter with irregular cycles (n = 5). This sample was not adequate to investigate possible swing of fibromyalgic symptoms throughout the menstrual cycle. Finally, we read with great interest the hypothesis that the lack of efficacy of oxytocin may be due to the use of nonsteroidal anti-inflammatory drugs (NSAIDs) [1]. This hypothesis was based on the results of three clinical