Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 56 11 2019 01 15 720 725 EN Poroshat Nazemi Nurse Anesthetist, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. Amir Hossein Orandi Department of Anesthesiology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. Amir Ali Orandi Department of Anesthesiology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. Amir Poya Zanjani Department of Anesthesiology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. Hossein Majedi Department of Anesthesiology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. Mojgan Rahimi Department of Anesthesiology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. Kasra Karvandian Department of Anesthesiology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. Fardin Yousefshahi Department of Anesthesiology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. Atieh Sedighian Nurse Anesthetist, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. Seyed Ali Emami Department of Anesthesiology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. 2017 12 23 2018 07 28 Clonidine, the α2-adrenergic agonist, is usually used as an antihypertensive drug. Dextromethorphan is a non-competitive NMDA antagonist which is routinely prescribed to suppress cough. However, there are not confidential documents regarding their analgesic effects. Due to the controversies over the analgesic properties of these two drugs, this study was designed to evaluate cold pain threshold changes following their administration. This study was conducted to assess the impact of oral clonidine and dextromethorphan on ice-water immersion tolerance. Four closed sachets labeled with codes were dedicated to each participant. Each of these four sachets contained placebo, 0.3 mg/kg dextromethorphan, 0.2 mg clonidine or both of the previous drugs randomly. The cold pain threshold was measured five times for each participant, once before taking any drug (T1) and the next four times (T2-T5) after taking each of the four sachets. 35 volunteers (15 men and 20 women) participated in the study. The study showed that cold pain threshold was higher in men than women (P=0.004) and also in participants above 30 than those under 30-year-old (P=0.007). Moreover, the pain threshold did not change significantly after the administration of clonidine (P=0.33) or dextromethorphan (P=0.21), but the threshold significantly increased after receiving a combination of dextromethorphan and clonidine compared with placebo overall (P=0.001). Cold pain threshold was higher in men and individuals over than 30-year-old and decreased significantly after administration of clonidine and dextromethorphan conjointly. Body mass index has no relation with changes in cold pain threshold by taking mentioned medications. https://acta.tums.ac.ir/index.php/acta/article/view/6906 https://acta.tums.ac.ir/index.php/acta/article/download/6906/5183