///2010 Abstract Details
2010 Abstract Details2018-05-01T17:52:49+00:00

Central oxytocin reduces hypersensitivity from injury, but not labor pain

Abstract Number: 125
Abstract Type: Original Research

James C. Eisenach M.D.1 ; Baogang Liu M.D., Ph.D.2; Chuanyao Tong M.D.3

Introduction

Chronic pain after childbirth is remarkably rare compared to surgery, suggesting a protective mechanism. We probed the time course of this protection in rats as well as tested the role of central oxytocin on labor pain behaviors.

Methods

Following ACUC approval, female rats were anesthetized and the L5 and L6 spinal nerves were ligated (SNL), a nerve injury model of chronic neuropathic pain. An intrathecal catheter of guide cannula into the paraventricular nucleus (PVN) was inserted in some rats. Withdrawal threshold to von Frey filaments was determined. Animals without SNL were video recorded during labor and their behaviors scored. Groups were compared by a two-way repeated measures ANOVA with P < 0.05 considered significant.

Results

SNL, performed in mid-pregnancy, reduced withdrawal threshold from 16 1.2 g before to 2.6 0.3 g 1 week after surgery (n=20). Withdrawal threshold increased from the day of delivery (3.3 0.4 g) to 8.2 0.6 g 24 days later, then abruptly decreased to 2.6 0.2 g when the pups were weaned. This effect was not observed if the pups were removed on the day of delivery (withdrawal threshold remained 2.9 - 4.4 g; n=5). Surrogate pups presented to virgin female rats with SNL surgery did not affect their withdrawal threshold (3.8 1.1 g before pups, 2.7-5.5 g with pups over 10 days; n=6).

At the time of postpartum partial inhibition of SNL hypersensitivity (withdrawal threshold 8.4 0.6 g; n=13), intrathecal injection of naloxone, 10 mcg did not affect withdrawal threshold (8.7 1 g), whereas injection of the selective oxytocin receptor antagonist, 1-deamino-2D-Tyr(Oethyl)-4-Thr-8-Orn-oxytocin, 12 mcg, reduced withdrawal threshold to 2.9 0.3 g. Infusion of phentolamine (500 nL, 3 mM), into the PVN also reduced withdrawal threshold from 13 1.2 g to 7.2 1.1 g, whereas vehicle infusion into the PVN had no effect (12 1.4 g before, 13 1.5 g after).

To determine whether central oxytocin alters labor pain behaviors, oxytocin, 1 microM/hr, was infused beginning the day before delivery. The number of contraction related nocifensive behaviors during labor in these animals (105 10/hr), did not differ with those receiving vehicle (125 31/hr). In contrast, intrathecal morphine, 1 mcg/hr, nearly abolished these behaviors (0.8 0.5/hr),

Discussion

These data suggest that both delivery and presence of pups were important to a reduction in hypersensitivity from pre-existing injury in postpartum rats. The effect was blocked by a spinal inhibitor of oxytocin receptors and an inhibitor of oxytocin neuron excitation in the PVN (phentolamine), consistent with activation of descending oxytocin inhibition to the spinal cord. These data suggest that increased central oxytocin tone may participate in protection against chronic pain after childbirth, but not from labor pain itself.

Supported in part by NIH grant GM48085

SOAP 2010