This article reviews material presented at the 2016 Scottsdale Headache Symposium. This presentation provided scientific results and rationale for the use of intranasal oxytocin for the treatment of migraine headache. Results from preclinical experiments are reviewed, including in vitro experiments demonstrating that trigeminal ganglia neurons possess oxytocin receptors and are inhibited by oxytocin. Furthermore, most of these same neurons contain CGRP, the release of which is inhibited by oxytocin. Results are also presented which demonstrate that nasal oxytocin inhibits responses of trigeminal nucleus caudalis neurons to noxious stimulation using either noxious facial shock or nitroglycerin infusion. These studies led to testing the analgesic effect of intranasal oxytocin in episodic migraineurs-studies which did not meet their primary endpoint of pain relief at 2 h, but which were highly informative and led to additional rat studies wherein inflammation was found to dramatically upregulate the number of oxytocin receptors available on trigeminal neurons. This importance of inflammation was supported by a series of in vivo rat behavioral studies, which demonstrated a clear craniofacial analgesic effect when a pre-existing inflammatory injury was present. The significance of inflammation was further solidified by a small single-dose clinical study, which showed analgesic efficacy that was substantially stronger in chronic migraine patients that had not taken an anti-inflammatory drug within 24 h of oxytocin dosing. A follow-on open label study examining effects of one month of intranasal oxytocin dosing did show a reduction in pain, but a more impressive decrease in the frequency of headaches in both chronic and high frequency episodic migraineurs. This study led to a multicountry double blind, placebo controlled study studying whether, over 2 months of dosing, "as needed" dosing of intranasal oxytocin by chronic and high frequency migraineurs would reduce the frequency of their headaches compared to a 1-month baseline period. This study failed to meet its primary endpoint, due to an extraordinarily high placebo rate in the country of most of the patients (Chile), but was also highly informative, showing strong results in other countries and strong post hoc indications of efficacy. The results provide a strong argument for further development of intranasal oxytocin for migraine prophylaxis.

Oxytocin receptor expression in calcitonin gene-related peptide containing trigeminal ganglion neurons, and the blockade of calcitonin gene-related peptide release from trigeminal dural afferents suggests that activation of these receptors may provide therapeutic benefit in patients with migraine and other primary headache disorders.

LOFTIN, MARK, MELINDA SOTHERN, LAURA TROSCLAIR, ANN O'HANLON, JAMES MILLER, AND JOHN UDALL. Scaling VO 2 peak in obese and non-obese girls. Obes Res. 2001;9:290 -296. Objective: The conventional ratio method (milliliters O 2 per mass) typically is used to express VO 2 peak. The goal of the current study was to compare VO 2 peak of obese girls with normal-weight girls by ratio and allometric scaling methods. Research Methods and Procedures: We compared VO 2 peak by ratio and allometric methods in 46 obese and 47 normal-weight girls. Indirect calorimetry was used to measure VO 2 peak during either treadmill running or walking. Regression analysis was used to determine coefficients for mass and stature for each group with ANOVA used to compare data between groups. Results: The obese girls were taller and had higher values of body fatness (p Յ 0.05). Absolute VO 2 peak (liters per minute) was similar between groups; however VO 2 peak relative to mass was 50% lower (p Յ 0.05) in the obese girls. When VO 2 peak (milliliters per minute per kilogram) and mass were correlated, r ϭ Ϫ0.48 was found in the obese group. Allometric scaling of logarithmic transformed stature and mass reduced this to r ϭ Ϫ0.002, thus eliminating the bias associated with the ratio method. Adjusting VO 2 peak allometrically scaled for mass, stature, and the combination of mass and stature reduced the difference between groups from 50% (ratio method) to 10% to 11% (p Յ 0.05) with higher values found in the normal-weight girls. Discussion: These results demonstrate the bias associated with the ratio method when comparing VO 2 peak in obese girls with VO 2 peak in normal-weight girls. Allometric scaling eliminated the bias and thus may reflect a truer comparative response.

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Severe thermal injury is associated with hypermetabolism and hypercatabolism, leading to skeletal muscle breakdown, lean body mass loss, weight loss, and negative nitrogen balance. Muscle protein catabolism in patients with severe thermal injury is the result of stress-induced increased release of cytokines and counterregulatory hormones. Coupled with decreased serum anabolic hormone concentrations such as testosterone and growth hormone along with the presence of insulin resistance, anabolism in patients with severe thermal injury is inefficient or impossible during the acute postburn period. This causes difficulty in restoring lean body mass and regaining lost body weight, as well as poor healing of the burn wound and delayed patient recovery. Oxandrolone, a synthetic derivative of testosterone, has been used in adult patients with severe thermal injury to enhance lean body mass accretion, restore body weight, and accelerate wound healing. In clinical studies, oxandrolone 10 mg orally twice/day improved wound healing, restored lean body mass, and accelerated body weight gain. During the rehabilitation period, oxandrolone therapy with adequate nutrition and exercise improved lean body mass, increased muscle strength, and restored body weight. However, most data on oxandrolone use in adult patients with severe thermal injury are derived from single-center studies, many of which enrolled a relatively small number of subjects and some of which had a poor design. Multicenter, prospective, randomized studies are needed to better define the optimal oxandrolone dosage and to confirm the efficacy and safety of this drug in adult patients with severe thermal injury.