Anesth Pain Med.  2016 Jul;11(3):236-248. 10.17085/apm.2016.11.3.236.

Mechanisms of postoperative pain

• Kang S
• Brennan TJ

• KMID: 2344925
• DOI: http://doi.org/10.17085/apm.2016.11.3.236

Abstract

Good pain control after surgery is important to facilitate overall recovery, improve patient satisfaction, decrease morbidity, and reduce health care cost. However, despite heightened awareness and development of new guidelines in recent decades, we have failed to make major improvements in postoperative pain control. Currently available analgesic therapies have limited efficacy, and pain after surgery continues to be a significant clinical problem. Our goal is to develop more effective and safer clinical strategies that will eliminate or greatly reduce postoperative pain, and a better understanding of the mechanisms of pain induced by surgery would be essential to achieve this goal. Evidence suggests that the pathophysiological mechanisms and optimal treatment of postoperative pain are different from many other painful conditions. Recognizing the necessity and importance of relevant pre-clinical models, we have developed and characterized rodent incision models that have close similarities to postoperative pain in patients. Previous studies have demonstrated the clinical relevance and translatability of these pre-clinical models of postoperative pain. In this review, we describe the rodent incision pain models, and summarized our current understanding of the mechanisms of postoperative pain, highlighting key findings from our previous studies using these models.

Keyword

Central sensitization; Incision; Peripheral sensitization; Postoperative pain; Post-surgical pain

MeSH Terms

Central Nervous System Sensitization
Health Care Costs
Humans
Pain, Postoperative*
Patient Satisfaction
Rodentia

Figure

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  Fig. 1 Rat plantar incision model. (A, B) A 1 cm longitudinal incision is made through skin and fascia, starting 0.5 cm from the proximal edge of the heel. (C, D) The flexor digitorum brevis muscle is elevated and incised longitudinally, with the muscle origin and insertion remained intact. (E, F) After hemostasis, the skin is closed with two mattress sutures.

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  Fig. 2 Guarding pain behavior after incision. The position of both paws are observed during 1 min period repeated every 5 min, and a score of 0, 1, or 2 is given, depending of the position in which each paw is found during the majority of the 1 min period; (A) A score of 0 is given for full weight bearing of the paw, causing blanching or distortion of the wound by the mesh; (B) A score of 1 is given if the area of the wound touches the mesh without blanching or distorting; (C) A score of 2 is given if the paw is completely off the mesh. The sum of the twelve scores recorded during 1 h session for each paw is obtained, and the cumulative pain score is the difference between the scores from the incised and non-incised paw.

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  Fig. 3 Summary of chemical responses of nociceptors to lactic acid of three different pH levels. (A) Sample recordings from one single C-fiber innervating ≤ 2 mm from the incision. After a 5-min baseline, 15 mM lactic acid with pH 6.5, 6.0 and 5.5 was sequentially applied for 5 min, followed by 5-min washout. The interval between each acid application was 15 min. The upper and lower panels show the digitized oscilloscope tracings and spike density histograms (bin width = 10 s), respectively. Inset displays the action potential of this unit. CV = conduction velocity. (B, C) Prevalence of acid-responsive units in C-fibers (B) and A-fibers (C). (D) Mean discharge rate of each acid-responsive C-fiber during application of 15 mM lactic acid with three different pH levels. Imp = impulse. Reprinted from Anesthesiolgoy, Vol. 111, S. Kang and T. J. Brennan, “Chemosensitivity and mechanosensitivity of nociceptors from incised rat hindpaw skin,” p 155-164, 2009, with permission from Wolters Kluwer Health, Inc.

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  Fig. 4 Time course changes in tissue pH, lactate concentration, and tissue oxygen tension after gastrocnemius muscle (A), paraspinal skin (B) and plantar (C) incision. A decrease in tissue oxygen tension occurs concurrently with a decrease in pH and an increase in lactate after incision. By postoperative day 10, tissue oxygen tension, lactate, and pH have returned to that of the control. The area shaded in gray represents the time after incision when pain-related behaviors are observed. Control is the value for the contralateral un-incised site. Error bars were omitted for simplicity. (Adapted and modified from reference [23] & [22]). Reprinted from Wound Repair Regen, Vol. 21, S. Kang and et al., “Wound hypoxia in deep tissue after incision in rats,” p 730-739, 2013, with permission from John Wiley and Sons.

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