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

Abstract

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.

Changes of heat pain sensitivity during the menstrual cycle in Japanese young adults: a randomized trial

“…Moreover, Piroli et al have shown that healthy young women exhibit lower postoperative pain sensitivity by undergoing gynecological laparoscopy in the follicular phase compared with that in the luteal phase 9) . Furthermore, results of the present study agree with recent findings that pinprick evoked pain, incision-induced pain, and mechanical hyperalgesia were significantly greater during the luteal phase compared to the follicular phase in female volunteers 10) . Moreover, the VAS scores of pain intensity, in relation to the pain threshold, were not significantly different between the two phases in the present study.…”

Human surrogate models of central sensitization: A critical review and practical guide

“…The model did not entail brush allodynia. In women, both the intensity and extent of hyperalgesia were found sensitive to the hormonal phases (Pogatzki‐Zahn et al., 2019 ). Systemic lidocaine previous to incision prevented 2HA, while neither subcutaneous nor systemic lidocaine reverted hyperalgesia once it was fully developed (Kawamata, Takahashi, et al., 2002 ; Kawamata, Watanabe, et al., 2002 ).…”

Within-session test-retest reliability of pressure pain threshold and mechanical temporal summation in healthy subjects

“…It is acknowledged that factors such as race/ethnicity, sex (e.g. phases of menstrual cycle [65]) and age could influence pain sensitivity [66,67], but considering that we measured reliability of pain sensitivity in a single session rather than pain sensitivity per se, the effect of these factors on our results remain limited. Future studies must be conducted in chronic pain participants, such as chronic low back pain.…”