Short-Term Sleep Disturbance-Induced Stress Does not Affect Basal Pain Perception, but Does Delay Postsurgical Pain Recovery

J Pain. 2015 Nov;16(11):1186-99. doi: 10.1016/j.jpain.2015.07.006. Epub 2015 Sep 3.


Chronic sleep disturbance-induced stress is known to increase basal pain sensitivity. However, most surgical patients frequently report short-term sleep disturbance/deprivation during the pre- and postoperation periods and have normal pain perception presurgery. Whether this short-term sleep disturbance affects postsurgical pain is elusive. Here, we report that pre- or postexposure to rapid eye movement sleep disturbance (REMSD) for 6 hours daily for 3 consecutive days did not alter basal responses to mechanical, heat, and cold stimuli, but did delay recovery in incision-induced reductions in paw withdrawal threshold to mechanical stimulation and paw withdrawal latencies to heat and cold stimuli on the ipsilateral side of male or female rats. This short-term REMSD led to stress shown by an increase in swim immobility time, a decrease in sucrose consumption, and an increase in the level of corticosterone in serum. Blocking this stress via intrathecal RU38486 or bilateral adrenalectomy abolished REMSD-caused delay in recovery of incision-induced reductions in behavioral responses to mechanical, heat, and cold stimuli. Moreover, this short-term REMSD produced significant reductions in the levels of mu opioid receptor and kappa opioid receptor, but not Kv1.2, in the ipsilateral L4/5 spinal cord and dorsal root ganglia on day 9 after incision (but not after sham surgery).

Perspective: Our findings show that short-term sleep disturbance either pre- or postsurgery does not alter basal pain perception, but does exacerbate postsurgical pain hypersensitivity. The latter may be related to the reductions of mu and kappa opioid receptors in the spinal cord and dorsal root ganglia caused by REMSD plus incision. Prevention of short-term sleep disturbance may help recovery from postsurgical pain in patients.

Keywords: Short-term sleep disturbance; postoperative pain; stress; surgery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Disease
  • Corticosterone / blood
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Hormone Antagonists / pharmacology
  • Kv1.2 Potassium Channel / metabolism
  • Lumbar Vertebrae
  • Male
  • Mifepristone / pharmacology
  • Pain Perception / drug effects
  • Pain Perception / physiology*
  • Pain, Postoperative / drug therapy
  • Pain, Postoperative / physiopathology*
  • Rats, Sprague-Dawley
  • Receptors, Opioid, kappa / metabolism
  • Receptors, Opioid, mu / metabolism
  • Sleep Wake Disorders / drug therapy
  • Sleep Wake Disorders / physiopathology*
  • Sleep, REM / physiology
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • Stress, Physiological / drug effects
  • Stress, Physiological / physiology*


  • Hormone Antagonists
  • Kv1.2 Potassium Channel
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Mifepristone
  • Corticosterone