Skip to main content

Advertisement

SpringerLink
Log in

Chronification of Pain: Mechanisms, Current Understanding, and Clinical Implications

  • Other Pain (A Kaye and N Vadivelu, Section Editors)
  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The development of acute to chronic pain involves distinct pathophysiological changes in the peripheral and central nervous systems. This article reviews the mechanisms, etiologies, and management of chronic pain syndromes with updates from recent findings in the literature.

Recent Findings

Chronic post-surgical pain (CPSP) is not limited to major surgeries and can develop after smaller procedures such as hernia repairs. While nerve injury has traditionally been thought to be the culprit for CPSP, it is evident that nerve-sparing surgical techniques are not completely preventative. Regional analgesia and agents such as ketamine, gabapentinoids, and COX-2 inhibitors have also been found to decrease the risks of developing chronic pain to varying degrees. Yet, given the correlation of central sensitization with the development of chronic pain, it is reasonable to utilize aggressive multimodal analgesia whenever possible.

Summary

Development of chronic pain is typically a result of peripheral and central sensitization, with CPSP being one of the most common presentations. Using minimally invasive surgical techniques may reduce the risk of CPSP. Regional anesthetic techniques and preemptive analgesia should also be utilized when appropriate to reduce the intensity and duration of acute post-operative pain, which has been correlated with higher incidences of chronic pain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Pergolizzi J, Ahlbeck K, Aldington D, Alon E, Coluzzi F, Dahan A, et al. The development of chronic pain: physiological CHANGE necessitates a multidisciplinary approach to treatment. Curr Med Res Opin. 2013;29(9):1127–35. https://doi.org/10.1185/03007995.2013.810615.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Alford DP, Krebs EE, Chen IA, Nicolaidis C, Bair MJ, Liebschutz J. Update in pain medicine. J Gen Intern Med. 2010;25(11):1222–6. https://doi.org/10.1007/s11606-010-1452-4.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Voscopoulos C, Lema M. When does acute pain become chronic? Br J Anaesth. 2010;105(Suppl 1):i69–85. https://doi.org/10.1093/bja/aeq323.

    Article  PubMed  Google Scholar 

  4. Butterworth JF, Mackey DC, Wasnick JD. Morgan and Mikhail’s clinical anesthesiology. 5th ed. New York: McGraw-Hill Education; 2013.

    Google Scholar 

  5. Sandkühler J. Models and mechanisms of hyperalgesia and allodynia. Physiol Rev. 2009;89(2):707–58. https://doi.org/10.1152/physrev.00025.2008.

    Article  PubMed  Google Scholar 

  6. Sivilotti L, Woolf CJ. The contribution of GABAA and glycine receptors to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord. J Neurophysiol. 1994;72(1):169–79. https://doi.org/10.1152/jn.1994.72.1.169.

    Article  CAS  PubMed  Google Scholar 

  7. Baba H, Ji R-R, Kohno T, Moore KA, Ataka T, Wakai A, et al. Removal of GABAergic inhibition facilitates polysynaptic A fiber-mediated excitatory transmission to the superficial spinal dorsal horn. Mol Cell Neurosci. 2003;24(3):818–30. https://doi.org/10.1016/S1044-7431(03)00236-7.

    Article  CAS  PubMed  Google Scholar 

  8. Woolf CJ, Thompson SW. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain. 1991;44(3):293–9. https://doi.org/10.1016/0304-3959(91)90100-C.

    Article  CAS  PubMed  Google Scholar 

  9. Woolf CJ, Shortland P, Coggeshall RE. Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature. 1992;355(6355):75–8. https://doi.org/10.1038/355075a0.

    Article  CAS  PubMed  Google Scholar 

  10. Crombie IK, Davies HT, Macrae WA. Cut and thrust: antecedent surgery and trauma among patients attending a chronic pain clinic. Pain. 1998;76(1–2):167–71. https://doi.org/10.1016/S0304-3959(98)00038-4.

    Article  CAS  PubMed  Google Scholar 

  11. De Kock M. Expanding our horizons: transition of acute postoperative pain to persistent pain and establishment of chronic postsurgical pain services. Anesthesiology. 2009;111(3):461–3. https://doi.org/10.1097/ALN.0b013e3181afde28.

    Article  PubMed  Google Scholar 

  12. Reddi D, Curran N. Chronic pain after surgery: pathophysiology, risk factors and prevention. Postgrad Med J. 2014;90(1062):222–7. https://doi.org/10.1136/postgradmedj-2013-132215.

    Article  CAS  PubMed  Google Scholar 

  13. Nomori H, Horio H, Fuyuno G, Kobayashi R. Non-serratus-sparing antero-axillary thoracotomy with disconnection of anterior rib cartilage. Improvement in postoperative pulmonary function and pain in comparison to posterolateral thoracotomy. Chest. 1997;111(3):572–6. https://doi.org/10.1378/chest.111.3.572.

    Article  CAS  PubMed  Google Scholar 

  14. Tasmuth T, Blomqvist C, Kalso E. Chronic post-treatment symptoms in patients with breast cancer operated in different surgical units. Eur J Surg Oncol: J Eur Soc Surg Oncol Br Assoc Surg Oncol. 1999;25(1):38–43.

    Article  CAS  Google Scholar 

  15. Stiff G, Rhodes M, Kelly A, Telford K, Armstrong CP, Rees BI. Long-term pain: less common after laparoscopic than open cholecystectomy. Br J Surg. 1994;81(9):1368–70. https://doi.org/10.1002/bjs.1800810939.

    Article  CAS  PubMed  Google Scholar 

  16. Maguire MF, Latter JA, Mahajan R, Beggs FD, Duffy JP. A study exploring the role of intercostal nerve damage in chronic pain after thoracic surgery. Eur J Cardiothorac Surg. 2006;29(6):873–9. https://doi.org/10.1016/j.ejcts.2006.03.031.

    Article  PubMed  Google Scholar 

  17. Carpenter JS, Sloan P, Andrykowski MA, McGrath P, Sloan D, Rexford T, et al. Risk factors for pain after mastectomy/lumpectomy. Cancer Pract. 1999;7(2):66–70. https://doi.org/10.1046/j.1523-5394.1999.07208.x.

    Article  CAS  PubMed  Google Scholar 

  18. Peters ML, Sommer M, de Rijke JM, Kessels F, Heineman E, Patijn J, et al. Somatic and psychologic predictors of long-term unfavorable outcome after surgical intervention. Ann Surg. 2007;245(3):487–94. https://doi.org/10.1097/01.sla.0000245495.79781.65.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Leslie TA, Illing RO, Cranston DW, Guillebaud J. The incidence of chronic scrotal pain after vasectomy: a prospective audit. BJU Int. 2007;100(6):1330–3. https://doi.org/10.1111/j.1464-410X.2007.07128.x.

    Article  PubMed  Google Scholar 

  20. Hayes CJ, Painter JT. A comprehensive clinical review of opioid-induced allodynia: discussion of the current evidence and clinical implications. J Opioid Manag. 2017;13(2):95–103. https://doi.org/10.5055/jom.2017.0373.

    Article  PubMed  Google Scholar 

  21. Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145–61.

    PubMed  Google Scholar 

  22. Brandsborg B, Nikolajsen L, Hansen CT, Kehlet H, Jensen TS. Risk factors for chronic pain after hysterectomy: a nationwide questionnaire and database study. Anesthesiology. 2007;106(5):1003–12. https://doi.org/10.1097/01.anes.0000265161.39932.e8.

    Article  PubMed  Google Scholar 

  23. Max MB, Stewart WF. The molecular epidemiology of pain: a new discipline for drug discovery. Nat Rev Drug Discov. 2008;7(8):647–58. https://doi.org/10.1038/nrd2595.

    Article  CAS  PubMed  Google Scholar 

  24. Diatchenko L, Nackley AG, Tchivileva IE, Shabalina SA, Maixner W. Genetic architecture of human pain perception. Trends Genet. 2007;23(12):605–13. https://doi.org/10.1016/j.tig.2007.09.004.

    Article  CAS  PubMed  Google Scholar 

  25. Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain. 2006;7(4):281–9. https://doi.org/10.1016/j.jpain.2005.11.008.

    Article  PubMed  Google Scholar 

  26. Ossipov MH, Morimura K, Porreca F. Descending pain modulation and chronification of pain. Curr Opin Support Palliat Care. 2014;8(2):143–51. https://doi.org/10.1097/SPC.0000000000000055.

    PubMed  PubMed Central  Google Scholar 

  27. Jess P, Jess T, Beck H, Bech P. Neuroticism in relation to recovery and persisting pain after laparoscopic cholecystectomy. Scand J Gastroenterol. 1998;33(5):550–3.

    Article  CAS  PubMed  Google Scholar 

  28. Matta JA, Cornett PM, Miyares RL, Abe K, Sahibzada N, Ahern GP. General anesthetics activate a nociceptive ion channel to enhance pain and inflammation. Proc Natl Acad Sci U S A. 2008;105(25):8784–9. https://doi.org/10.1073/pnas.0711038105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pluijms WA, Steegers MH, Verhagen AFTM, Scheffer GJ, Wilder-Smith OHG. Chronic post-thoracotomy pain: a retrospective study. Acta Anaesthesiol Scand. 2006;50(7):804–8. https://doi.org/10.1111/j.1399-6576.2006.01065.x.

    Article  CAS  PubMed  Google Scholar 

  30. Werner MU, Mjöbo HN, Nielsen PR, Rudin A. Prediction of postoperative pain: a systematic review of predictive experimental pain studies. Anesthesiology. 2010;112(6):1494–502. https://doi.org/10.1097/ALN.0b013e3181dcd5a0.

    Article  PubMed  Google Scholar 

  31. Kaye AD, Helander EM, Vadivelu N, Lumermann L, Suchy T, Rose M et al. Consensus statement for clinical pathway development for perioperative pain management and care transitions. Pain Ther. 2017.

  32. Gritsenko K, Khelemsky Y, Kaye AD, Vadivelu N, Urman RD. Multimodal therapy in perioperative analgesia. Best Pract Res Clin Anaesthesiol. 2014;28(1):59–79. https://doi.org/10.1016/j.bpa.2014.03.001.

    Article  PubMed  Google Scholar 

  33. McCartney CJL, Sinha A, Katz J. A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia. Anesth Analg. 2004;98(5):1385–400.

    Article  CAS  PubMed  Google Scholar 

  34. Vadivelu N, Schermer E, Kodumudi V, Belani K, Urman RD, Kaye AD. Role of ketamine for analgesia in adults and children. J Anaesthesiol Clin Pharmacol. 2016;32(3):298–306. https://doi.org/10.4103/0970-9185.168149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. • Kim K, Mishina M, Kokubo R, Nakajima T, Morimoto D, Isu T, et al. Ketamine for acute neuropathic pain in patients with spinal cord injury. J Clin Neurosci: Off J Neurosurg Soc Australas. 2013;20(6):804–807. Study demonstrating ketamine effectiveness for treating acute neuropathic pain. https://doi.org/10.1016/j.jocn.2012.07.009.

    Article  CAS  Google Scholar 

  36. • Cogan J, Lalumière G, Vargas-Schaffer G, Deschamps A, Yegin Z. Low-dose intravenous ketamine for postcardiac surgery pain: effect on opioid consumption and the incidence of chronic pain. Ann Card Anaesth. 2017;20(4):395–398. Large meta-analyses demonstrating no improvement in long-term post-operative pain with ketamine. https://doi.org/10.4103/aca.ACA_54_17.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Clarke H, Bonin RP, Orser BA, Englesakis M, Wijeysundera DN, Katz J. The prevention of chronic postsurgical pain using gabapentin and pregabalin: a combined systematic review and meta-analysis. Anesth Analg. 2012;115(2):428–42. https://doi.org/10.1213/ANE.0b013e318249d36e.

    Article  CAS  PubMed  Google Scholar 

  38. Han C, Li X-D, Jiang H-Q, Ma J-X, Ma X-L. The use of gabapentin in the management of postoperative pain after total knee arthroplasty: a PRISMA-compliant meta-analysis of randomized controlled trials. Medicine. 2016;95(23):e3883. https://doi.org/10.1097/MD.0000000000003883.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sugita R, Kuwabara H, Kubota K, Sugimoto K, Kiho T, Tengeiji A, et al. Simultaneous inhibition of PGE2 and PGI2 signals is necessary to suppress hyperalgesia in rat inflammatory pain models. Mediat Inflamm. 2016;2016:9847840.

    Article  Google Scholar 

  40. Vigneault L, Turgeon AF, Côté D, Lauzier F, Zarychanski R, Moore L, et al. Perioperative intravenous lidocaine infusion for postoperative pain control: a meta-analysis of randomized controlled trials. Can J Anaesth. 2011;58(1):22–37. https://doi.org/10.1007/s12630-010-9407-0.

    Article  PubMed  Google Scholar 

  41. Chung M-K, Campbell JN. Use of capsaicin to treat pain: mechanistic and therapeutic considerations. Pharmaceuticals (Basel). 2016;9(4).

  42. Carr DB, Goudas LC. Acute pain. Lancet (London, England). 1999;353(9169):2051–8. https://doi.org/10.1016/S0140-6736(99)03313-9.

    Article  CAS  Google Scholar 

  43. •• Marin TJ, Van Eerd D, Irvin E, Couban R, Koes BW, Malmivaara A, et al. Multidisciplinary biopsychosocial rehabilitation for subacute low back pain. Cochrane Database Syst Rev. 2017;6:CD002193. Article demonstrating importance of multidisciplinary approach for chronic pain management

    PubMed  Google Scholar 

  44. Wickson-Griffiths A, Kaasalainen S, Herr K. Interdisciplinary approaches to managing pain in older adults. Clin Geriatr Med. 2016;32(4):693–704. https://doi.org/10.1016/j.cger.2016.06.013.

    Article  PubMed  Google Scholar 

  45. •• Allaire C, Williams C, Bodmer-Roy S, Zhu S, Arion K, Ambacher K, et al. Chronic pelvic pain in an interdisciplinary setting: 1 year prospective cohort. A Am J Obstet Gynecol. 2017;17:31184–5. Study demonstrating long-term efficacy of multidisciplinary team approach for chronic pelvic pain

    Google Scholar 

  46. Rasmussen C, Nielsen GL, Hansen VK, Jensen OK, Schioettz-Christensen B. Rates of lumbar disc surgery before and after implementation of multidisciplinary nonsurgical spine clinics. Spine. 2005;30(21):2469–73. https://doi.org/10.1097/01.brs.0000184686.70838.96.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Daniel J. Pak, R. Jason Yong & Richard D. Urman

  2. Department of Anesthesiology, School of Medicine, Louisiana State University, New Orleans, LA, 70112, USA

    Alan David Kaye

Authors
  1. Daniel J. Pak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Jason Yong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan David Kaye
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard D. Urman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard D. Urman.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Other Pain

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pak, D.J., Yong, R.J., Kaye, A.D. et al. Chronification of Pain: Mechanisms, Current Understanding, and Clinical Implications. Curr Pain Headache Rep 22, 9 (2018). https://doi.org/10.1007/s11916-018-0666-8

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11916-018-0666-8

Keywords

Search

Navigation