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Progesterone relates to enhanced incisional acute pain and pinprick hyperalgesia in the luteal phase of female volunteers

Pogatzki-Zahn, Esther M.a,*; Drescher, Christianea; Englbrecht, Jan S.a; Klein, Thomasb; Magerl, Walterb; Zahn, Peter K.c

doi: 10.1097/j.pain.0000000000001561
Research Paper

The role of sex hormones on postsurgical pain perception is basically unclear. Here, we studied the role of endogenous gonadal hormones for pain and hyperalgesia in human volunteers after experimental incision. A 4-mm incision was made in the volar forearm of 15 female volunteers both in the follicular and the luteal phase (random block design). Somatosensory profiles were assessed at baseline and 1 to 72 hours after incision by quantitative sensory testing, compared between both cycle phases, and related to individual plasma levels of gonadal hormones. Sensory testing at baseline revealed significantly lower pain thresholds (25 vs 46 mN, P < 0.005) and increased pain ratings to pinprick (0.96 vs 0.47, P < 0.0001) in the luteal phase; similarly, 1 hour after incision, pain intensity to incision (38 vs 21/100, P < 0.005), pinprick hyperalgesia by rating (P < 0.05), and area of secondary hyperalgesia (P < 0.001) were enhanced in the luteal phase. Multiple regression analysis revealed that pinprick pain sensitivity at baseline was significantly predicted by progesterone (partial r = 0.67, P < 0.001), follicle-stimulating hormone (FSH) (partial r = 0.61, P < 0.005), and negatively by testosterone (partial r = −0.44, P < 0.05). Likewise, incision-induced pain and pinprick hyperalgesia (rating and area) were significantly predicted by progesterone (partial r = 0.70, r = 0.46, and r = 0.47, respectively; P < 0.05-0.0001) and in part by FSH; the contribution of estrogen, however, was fully occluded by progesterone for all measures. In conclusion, pinprick pain and incision-induced pain and mechanical hyperalgesia were greater in the luteal phase and predicted by progesterone, suggesting a major role for progesterone. Other hormones involved are testosterone (protective) and in part FSH.

In healthy female volunteers, pinprick-evoked pain and pain and hyperalgesia after experimental incision were substantially modulated by endogenous sex hormones (eg, progesterone and testosterone).

aDepartment of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital of Muenster, Muenster, Germany

bDepartment of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim (CBTM), University Medicine Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany. Dr. Klein is now with Mundipharma Research GmbH & Co., KG, Limburg (Lahn), Germany

cDepartment of Anaesthesiology, Intensive Care Medicine, Palliative Care Medicine and Pain Management, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH Bochum, Ruhr University Bochum, Bochum, Germany

Corresponding author. Address: Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Albert-Schweitzer-Campus 1, A1 48149 Muenster, Germany. Tel.: 0049-251-8347261; fax: 0049-251-88704. E-mail address: (E.M. Pogatzki-Zahn).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

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W. Magerl and P.K. Zahn contributed equally to this work.

Received September 03, 2018

Received in revised form March 07, 2019

Accepted March 09, 2019

Online date: March 21, 2019

© 2019 International Association for the Study of Pain
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