Pain Medicine  |   September 2018
Plasticity and Function of Spinal Oxytocin and Vasopressin Signaling during Recovery from Surgery with Nerve Injury
Amie L. Severino, Ph.D.; Rong Chen, Ph.D.; Kenichiro Hayashida, D.V.M., Ph.D.; Carol A. Aschenbrenner, M.A.; Haiguo Sun, Ph.D.; et al Christopher M. Peters, Ph.D.; Silvia Gutierrez, Ph.D.; Bethany Pan, B.S.; James C. Eisenach, Ph.D.
Author Notes
  • From the Departments of Anesthesiology (A.L.S., K.H., C.A.A., C.M.P., S.G., J.C.E.); Physiology and Pharmacology (R.C., H.S., J.C.E.); and School of Medicine (B.P.), Wake Forest School of Medicine, Winston-Salem, North Carolina.
  • Submitted for publication May 10, 2017. Accepted for publication May 4, 2018.
    Submitted for publication May 10, 2017. Accepted for publication May 4, 2018.×
  • Address correspondence to Dr. Eisenach: Department of Anesthesiology, Wake Forest School of Medicine, 1 Medical Center Boulevard, Winston-Salem, North Carolina, 27157. jimeisenach@gmail.com. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Basic Science / Central and Peripheral Nervous Systems / Obstetric Anesthesia / Pain Medicine
Pain Medicine   |   September 2018
Plasticity and Function of Spinal Oxytocin and Vasopressin Signaling during Recovery from Surgery with Nerve Injury
Anesthesiology 9 2018, Vol.129, 544-556. doi:10.1097/ALN.0000000000002290
Anesthesiology 9 2018, Vol.129, 544-556. doi:10.1097/ALN.0000000000002290
Abstract

What We Already Know about This Topic:

  • Pain resolves more quickly from cesarean delivery than other abdominal surgeries

  • Pregnancy-related hormones such as oxytocin may reduce postoperative pain in women, although similar systems may function in men as well

What This Article Tells Us That Is New:

  • Blockade of either oxytocin or vasopressin 1A receptors increased mechanical hypersensitivity in both male and female rats after partial spinal nerve ligation

  • Levels of oxytocin in the spinal cord as well as oxytocin and vasopressin 1A receptor expression were increased after spinal nerve ligation in rats of both sexes

Background: Recovery from pain after surgery is faster after cesarean delivery than after other abdominal procedures. The authors hypothesized that recovery in rats after surgery could be reversed by antagonism of spinal oxytocin or vasopressin receptors, that there may be a sex difference, and that spinal oxytocin innervation could change after surgery.

Methods: Male and female rats underwent partial spinal nerve ligation surgery. Effects of nonselective and selective oxytocin and vasopressin 1A receptor antagonists on mechanical hypersensitivity during partial recovery were assessed (n = 8 to 14/group). Oxytocin immunoreactivity in the dorsal horn of the spinal cord (n = 7 to 8/group) and messenger RNA (mRNA) expression for oxytocin-binding receptors in dorsal root ganglia and spinal cord (n = 8/group) were measured.

Results: Intrathecal injection of oxytocin and vasopressin receptor antagonists were similarly effective at reducing withdrawal threshold (in all experiments from 22 [19, 26] median [first quartile, third quartile]) g to 8.3 [6.4, 12] g after injection) in both sexes, while having no or minimal effects in animals without surgery. Oxytocin fiber immunoreactivity was 3- to 5-fold greater in lumbar than other regions of the spinal cord and was increased more than 2-fold in lumbar cord ipsilateral to surgery. Injury was also associated with a 6.5-fold increase in oxytocin receptor and a 2-fold increase in vasopressin 1A receptor messenger RNA expression in the L4 dorsal root ganglion ipsilateral to surgery.

Conclusions: : These findings suggest that the capacity for oxytocin signaling in the spinal cord increases after surgery and that spinal oxytocin signaling plays ongoing roles in both sexes in recovery from mechanical hypersensitivity after surgery with known nerve injury.