What causes pain following surgery?

During surgery, cutting of the tissues and nerve fibers causes an intense burst of nociceptive pain.1

Once tissues have been damaged, inflammatory pain increases sensitivity to the affected area and encourages patients to reduce movement of, or contact with, the injury until repair is complete to minimize further damage.1

Neuropathic pain is caused when the tissue trauma overloads the pain receptors that send messages to the spinal cord, which becomes overstimulated. In the resultant central sensitization, any stimulation becomes unpleasant; a patient may feel pain in movement or physical touch in locations far from the surgical site.1

All three types contribute to patient discomfort following surgery, but inflammation poses additional challenges for postoperative pain management.1

How long does acute postoperative pain last?

While the duration of postoperative pain varies widely depending on the procedure performed, severe pain usually lasts approximately 3 days, or 72 hours.2,3

Graph of patient pain intensity over 72 hours; 75% of patients are still in moderate to severe pain 48 hours after surgery.

How does acute postoperative pain become chronic?

Postoperative pain that persists longer than 3 months is considered to be chronic.4 Studies show that the severity of acute postoperative pain can be predictive of the development of chronic pain in a number of procedures. Unresolved, persistent postoperative pain can cause prolonged inflammatory states that induce changes in associated nociceptors, establishing the pathophysiology of chronic pain.4,5

Flowchart of how inadequate postoperative pain management during the first 72 hours can lead to chronic pain.

What is the difference between analgesics and anesthetics?

Analgesia is insensibility to pain without the loss of consciousness.6

Anesthesia is the loss of sensation with or without the loss of consciousness. General anesthesia affects the entire body and renders the patient unconscious, while local anesthesia only affects a limited part of the body.7

A notable difference between local anesthesia and analgesia is that anesthetics actually stop pain signals, while analgesics render the patient less able to perceive pain.6,7

How does local anesthesia work?

Local anesthetics can be a strong foundation for postoperative pain management and a first line of defense for patients. The target of the local anesthetic bupivacaine is the voltage-gated sodium ion channel. To prevent a pain signal from propagating along a nerve cell, bupivacaine must penetrate the cell membrane, become ionized, and then block these channels from inside the nerve cell, preventing the sodium ions from entering and changing the polarity of the nerve cell.8

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What is the duration of available local anesthetics?

Local anesthetics are an important tool in postoperative pain management because they reduce the amount of pain a patient feels when he or she wakes. But generic local anesthetics are not designed to provide pain relief beyond 8 to 12 hours, and longer-acting local anesthetics exhibit limited and inconsistent efficacy beyond 24 hours—in part because the inflammatory process inhibits their ability to penetrate the nerve cell membrane.

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What role does inflammation play following surgery?

The body’s inflammatory response is intended to promote the healing of damaged tissues by increasing sensitivity to movement and contact at the site of injury.1 The tissue damage activates nociceptor cells, which release inflammatory mediators.1,14 Inflammation is a significant driver of postoperative discomfort; it reaches its peak around 24 hours following surgery but continues to be high through the first 72 hours.1,15 And because inflammation can cause tissue acidosis, it can pose additional pain management challenges.16

Inflammation causes the surgical site to become flooded with acidic metabolites such as lactic acid, lowering pH at the surgical site and increasing the local concentration of hydrogen ions. This makes it more likely for the bupivacaine to become ionized. In its ionized form, bupivacaine is unable to penetrate the nerve cell membrane and therefore cannot block pain signals.1,14

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What are the pros and cons of opiate pain medication?

Opioids can be effective (and inexpensive) analgesics. Given that many available local anesthetics are not designed to last beyond 24 hours, opioids have been used to ease patients’ postoperative pain after local anesthetics have worn off.3,8,18

Opioids come with risks. In addition to the risk of long-term dependence and addiction, the adverse events associated with opioids can range from mildly problematic to life-threatening and may increase length of hospital stay for patients.19,20 Common adverse events include21:

  • Nausea
  • Vomiting
  • Pruritus
  • Somnolence
  • Urinary retention
  • Constipation
  • Respiratory depression

Some research also suggests that opioids may not be the most effective way to treat pain. Because opioid receptors are distributed throughout the central nervous system, opioids have a limited effect on the transmission of peripheral pain signals. In short, while opioids can mask the sensation of pain, they do not actually stop pain signals at the site of injury.22

Paradoxically, in some cases opioids can actually render patients more sensitive to pain. They can increase the production and release of nociceptive pain signals, enhance the facilitation of signal transmission, and make second-order neurons more sensitive to nociceptive signals. This is known as hyperalgesia.23

What are the American Society of Anesthesiologists' recommendations for the use of opioids and local anesthetics in postoperative pain management?

The ASA is dedicated to raising and maintaining the standards of the medical practice of anesthesiology and to improving patient care. They provide patient advocacy, education, research, and scientific knowledge to members. The ASA has developed a practice guideline for responsible pain management in the perioperative setting, which can be accessed here.

How many surgical patients become addicted to opioids?

More than 50 million surgical procedures happen in the United States each year; 90% of patients undergoing a surgical procedure are prescribed opioids for pain management. As many as 6.5% of those patients taking opioids for postoperative pain management may become persistent users of opioids. That equals 2.6 million people. Of those 2.6 million, 440,000 will become addicted to opioids.18-20

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References: 1. Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med. 2004;140(6):441-451. doi:10.7326/0003-4819-140-8-200404200-00010. 2. Svensson I, Sjöström B, Haljamäe H. Assessment of pain experiences after elective surgery. J Pain Symptom Manage. 2000;20(3):193-201. doi:10.1016/S0885-3924(00)00174-3. 3. Data on file. DRG Physician Survey. Heron Therapeutics; 2016. 4. Perkins FM, Kehlet H. Chronic pain as an outcome of surgery: a review of predictive factors. Anesthesiology. 2000;93(4):1123-1133. doi:10.1097/00000542-200010000-00038. 5. Voscopoulos C, Lema M. When does acute pain become chronic? Brit J Anaesth. 2010;105(suppl 1):i69-i85. doi:10.1093/bja/aeq323. 6. Analgesia. Merriam-Webster Website. 2019.https://www.merriam-webster.com/dictionary/analgesia. Accessed January 18, 2019. 7. Anesthesia. Merriam-Webster Website. 2019. https://www.merriam-webster.com/dictionary/anesthesia. Accessed January 18, 2019. 8. Berde CB, Strichartz GR. Local anesthetics. In: Miller RD, Cohen NH, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young WL, eds. Miller’s Anesthesia. Vol 2. 8th ed. Philadelphia, PA: Saunders; 2015:1012-1054.e4. 9. Gorfine SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Dis Colon Rectum. 2011;54(12):1552-1559. doi:10.1097/DCR.0b013e318232d4c1. 10. Brown L, Weir T, Shasti M, et al. The efficacy of liposomal bupivacaine in lumbar spine surgery. Int J Spine Surg. 2018;12(4):434-440. doi:10.14444/5052. 11. Ali A, Sundberg M, Hansson U, Malmvik J, Flivik G. Doubtful effect of continuous intraarticular analgesia after total knee arthroplasty: A randomized, double-blind study of 200 patients. Acta Orthopaedica. 2015;86(3):373-377. doi:10.3109/17453674.2014.991629. 12. Carvalho B, Clark DJ, Yeomans DC, Angst MS. Continuous subcutaneous instillation of bupivacaine compared to saline reduces interleukin 10 and increases substance P in surgical wounds after cesarean delivery. Anesth Analg. 2010;111(6):1452-1459. doi:10.1213/ANE.0b013e3181f579de. 13. Kim J, Burke SM, Kryzanski JT, et al. The role of liposomal bupivacaine in reduction of postoperative pain after transforaminal lumbar interbody fusion: a clinical study. World Neurosurg. 2016;91:460-467. doi:10.1016/j.wneu.2016.04.058. 14. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267-284. doi:10.1016/j.cell.2009.09.028. 15. Enoch S, Leaper DJ. Basic science of wound healing. Surgery (Oxford). 2007;26(2):31-37. doi:10.1016/j.mpsur.2007.11.005. 16. Hargreaves KM, Keiser K. Local anesthetic failure in endodontics: mechanisms and management. Endod Topics. 2002;1(1):26-39. doi:10.1034/j.1601-1546.2002.10103.x. 17. Vane JR, Botting R. Mechanism of action of anti-inflammatory drugs. FASEB J. 1987;1(2):89-96. doi:10.1096/fasebj.1.2.3111928. 18. Hill MV, McMahon ML, Stucke RS, Barth RJ Jr. Wide variation and excessive dosage of opioid prescriptions for common general surgical procedures. Ann Surg. 2017;265(4):709-714. doi:10.1097/SLA.0000000000001993. 19. Brummett CM, Waljee JF, Goesling J, et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg. 2017;152(6):e170504. doi:10.1001/jamasurg.2017.0504. 20. Banta-Green CJ, Merrill JO, Doyle SR, Boudreau DM, Calsyn DA. Opioid use behaviors, mental health and pain: development of a typology of chronic pain patients. Drug Alcohol Depend. 2009;104(1-2):34-42. doi:10.1016/j.drugalcdep.2009.03.021. 21. Kessler ER, Shah M, Gruschkus SK, Raju A. Cost and quality implications of opioid‐based postsurgical pain control using administrative claims data from a large health system: opioid‐related adverse events and their impact on clinical and economic outcomes. Pharmacotherapy. 2013;33(4):383-391. doi:10.1002/phar.1223. 22. Al-Hasani R, Bruchas MR. Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology. 2011;115(6):1363-1381. doi:10.1097/ALN.0b013e318238bba6. 23. Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145-161. http://www.painphysicianjournal.com/current/pdf?article=MTQ0Ng%3D%3D&journal=60. Accessed October 1, 2018.