Estrogen rapidly enhances incisional pain of ovariectomized rats primarily through the G protein-coupled estrogen receptor.

Guanghui An,Tao Yan,Wenhui Li,Shitong Li

doi:10.3390/ijms150610479

Abstract

It has become increasingly apparent that the pain threshold of females and males varies in an estrogen dependent manner. To investigate the modulation of pain by estrogen and the molecular mechanisms involved in this process. A total of 48 rats were ovariectomized (OVX). At 14 and 20 days after OVX, rats were divided into eight groups: groups 1–4 were administered drugs intravenously (IV); groups 5–8 were administered through intrathecal (IT) catheter. Hind paw incision was made in all animals to determine incisional pain. Paw withdraw threshold (PWT) was tested prior to and 24 h after incision. The test drugs were applied 24 h after the incision. Rats were either IV or IT administered with: 17-β-estradiol (E2), G protein-coupled estrogen receptor (GPER)-selective agonist (G1), GPER-selective antagonist (G15) and E2 (G15 + E2), or solvent. Before and 30 min after IV drug administration and 20 min during the IT catheter administration, PWT was tested and recorded. 24 h after incisional surgery, the PWT of all rats significantly decreased. Both in the IV group and IT group: administration of E2 and G1 significantly decreased PWT. Neither administration of G15 + E2 nor solvent significantly changed PWT. Estrogen causes rapid reduction in the mechanical pain threshold of OVX rats via GPER.

Highlights

It has been shown that estrogen can influence pain threshold
The basal mechanical pain thresholds of male and female rats vary in an estrogen-dependent manner [6]
There was no significant difference in paw withdraw threshold (PWT) between the groups before the incision surgery, and the PWT dropped significantly 24 h after the surgery (Table 1, Figure 1A–C)

Summary

Introduction

It has been shown that estrogen can influence pain threshold. In a study of healthy subjects, tested by a variety of stimuli including thermal stimulation, pressure stimulation and chemical stimulation, the pain threshold and tolerance were found to be lower in females than males [1,2,3,4]. Females suffered more from clinical pain disorders than males in terms of migraines and trigeminal neuralgia [5]. The basal mechanical pain thresholds of male and female rats vary in an estrogen-dependent manner [6]. Administration of estrogen has been shown to result in sensitization of nociceptive neurons, resulting in a decrease of the pain threshold [7,8].

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