Lactate concentrations in incisions indicate ischemic-like conditions may contribute to postoperative pain

J Pain. 2007 Jan;8(1):59-66. doi: 10.1016/j.jpain.2006.06.003. Epub 2006 Sep 1.


The substances in wounds that cause incisional pain and hyperalgesia after surgery are poorly understood. We have developed and characterized rat models for incision-induced pain behaviors and measured increased tissue hydrogen ion concentration. Because lactate may facilitate nociceptor responses to low pH and contribute to ischemic pain mechanisms, we measured tissue lactate after incision of the plantar region of the hindpaw, gastrocnemius muscle, and paraspinal region in halothane anesthetized rats using in vivo microdialysis. Incisions were performed at 1 site (plantar, gastrocnemius, or paraspinal incision) in each rat. The corresponding contralateral side was used as the control. In anesthetized rats, a microdialysis fiber was passed into the incision and the control side. L-Lactate was measured using the lactate oxidase method. Tissue concentration was determined from postoperative day 0 to postoperative day 14 using the no net flux method. Lactate was increased on the day of hindpaw incision to 3.6 +/- 1.6 mmol/L compared with control (2.1 +/- .6 mmol/L) and remained increased through 7 days. In the gastrocnemius muscle, lactate was increased the day after incision (4.2 +/- 1.2 mmol/L vs 1.7 +/- .5 mmol/L) until postoperative day 7. On the day of the paraspinal incision, lactate was 3.4 +/- 1.1 mmol/L on the operated side and 2.2 +/- .6 mmol/L in the control side. Lactate remained increased through postoperative day 8 at the paraspinal incision. These experiments demonstrate that incision of the plantar hindpaw, the gastrocnemius muscle, and the paraspinal region increased tissue lactate concentration. The wound environment contains increased lactate at the same time that pH is decreased; lactate could potentially facilitate nociceptor activation by low pH and contribute to pain after surgery.

Perspective: This study demonstrates that lactate is increased in wounds when pain behaviors and acid are increased. Lactate and low pH are present in incisions and indicate an ischemic pain mechanism that may contribute to postsurgical pain.

Publication types

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

MeSH terms

  • Anesthesia, Inhalation
  • Anesthetics, Inhalation
  • Animals
  • Behavior, Animal
  • Foot / blood supply
  • Foot / physiology
  • Halothane
  • Hindlimb / blood supply
  • Hindlimb / physiology
  • Hydrogen-Ion Concentration
  • Ischemia / metabolism*
  • Ischemia / pathology
  • Lactic Acid / metabolism*
  • Male
  • Microdialysis
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / physiology
  • Pain Measurement
  • Pain, Postoperative / metabolism*
  • Pain, Postoperative / pathology
  • Rats
  • Rats, Sprague-Dawley


  • Anesthetics, Inhalation
  • Lactic Acid
  • Halothane