Grünenthal uses its own and third-party cookies to improve the browsing experience, offer personalized content and improve its services. We use analytics scripts which set a tracking cookie, but we will activate these services only with your consent. If you press the button “Accept”, you consent to the use of these analytics scripts.

You can withdraw your consent at any time. To do so, please modify your configurations on this website by following this link to our privacy statement with the configuration options: Go to settings

I'm ok with this


Many chronic conditions are challenging to manage. Here we focus on eight key pain conditions with a high unmet need among patients and/or healthcare professionals.

Our aim here is to provide the pain community with in-depth information about these conditions; from disease understanding to management approaches.




Peri-surgical pain management refers to the actions taken before, during and after a surgical procedure to reduce or eliminate pain, up to discharge.1 If chronification of this pain occurs, it is termed chronic post-surgical pain (CPSP), a potentially devastating outcome from an otherwise successful surgical procedure.1,2 The most recent definition of CPSP is pain of at least 3–6 months’ duration that significantly affects the health-related quality of life of the patient.3 It can represent a severe complication for patients, leading to functional limitation and psychological trauma, as well as being a problem for the operative team in the form of feelings of frustration and disappointment.4


Quick facts

  • CPSP is a significant problem affecting millions of patients each year, with pain lasting for months or years post-procedure.2,5
  • There are multiple pre-, intra- and post-operative risk factors for the development of CPSP, such as comorbidities, minor versus major surgery and the strategy of post-surgical pain management.6,7
  • The development of CPSP is complex and multifactorial; it is thought to involve the interplay of patient factors, the inflammatory and immune response to tissue and nerve damage, and the surgical, anaesthetic and analgesic techniques applied.8
  • Diagnosis of CPSP is made if the pain is localised to the surgical field or is within the innervation territory of a nerve situated in the surgical field, and has persisted for 3–6 months post-surgery, with other causes of pain excluded.2




Surgery is recognised as one of the most frequent causes of chronic pain in patients attending pain clinics.9 It is estimated that acute post-operative pain will chronify in 10–50% of cases following common surgical operations.1 Therefore, CPSP affects millions of patients every year, with pain lasting from months to years, resulting in widespread patient suffering and ensuing economic consequences.2 The prevalence of CPSP varies by type of surgery; the operations with the highest incidence of CPSP are amputation, thoracotomy and breast surgery.2

Procedure-specific incidence of chronic post surgical pain 

CPSP: chronic post-surgical pain.

Risk factors

Several risk factors have been identified for the development of CPSP, and there is no single dominant factor.4 The risk determinants can be classified according to the timing of the surgery, with factors prior to, during and after the operation contributing to the risk of developing CPSP.6

One of the leading risk factors for CPSP is the extent of tissue damage during surgery and injury to the nerves during dissection or retraction.4 Nerves are at continuous risk of contusion, stretching, division or entrapment from insults such as surgical retraction, diathermy or compression with bones.4 It may be possible to reduce the risk by giving consideration to the surgical approach, pain management and psychological predisposition.9 Psychological risk factors are another important consideration; negative affective constructs such as anxiety, depression, pain catastrophisation and general psychological distress have been consistently identified as risk factors for CPSP.11

PAIN OUT, an international quality improvement and research network, is conducting research into peri-operative pain management in the clinical routine setting utilising a large registry.12 Recent data from the project suggest that educational interventions may improve processes.12

Risk factors for development of chronic post surgical pain 


Neuroplasticity (spinal sensitisation) following trauma may transform acute pain to chronic pain if not treated in a timely manner.4 However, the development of CPSP is thought to be multifactorial, involving the interplay of patient factors (e.g. psychology, genetics, pre-existing pain); the inflammatory response to tissue damage; and the surgical, anaesthetic and analgesic techniques applied.8

Main mechanisms causing surgical pain 

Signs and symptoms

The signs and symptoms of peri- and post-operative pain can be diverse because of the highly heterogeneous population and also because the amount of tissue injury and degree of inflammation varies widely by operation type and procedures utilised.4 Nerve injury during surgery has been implicated in the development of CPSP and some (but not all) patients with CPSP will present with evoked and spontaneous symptoms associated with neuropathic pain, such as allodynia and hyperalgesia.7 However, any link between nerve damage during surgery and the development of CPSP is complicated. Not all patients with nerve damage develop CPSP, and those who do develop CPSP do not necessarily have neuropathic pain.7


Symptoms of chronic post surgical pain 


Inflammatory and immune reactions after nerve damage to axons results in the release of neurotransmitters that act locally and in the spinal cord to produce hypersensitivity and ectopic neural activity; this contributes to central sensitisation.7 Central sensitisation occurs when repetitive nociceptive stimuli result in altered dorsal horn activity and amplification of sensory flow. This can lead to persistent nervous system changes, for example, death of inhibitory neurons, their replacement with excitatory afferent neurons, and microglial activation. These changes lead to symptoms associated with neuropathic pain.7


Sites and mechanisms responsible for chronic post surgical neuropathic pain 


Criteria for diagnosing CPSP were originally proposed in 1999, defining it as pain that developed after surgery lasting at least 2 months in duration.2 Other causes for the pain and the possibility that it might be continuing from the pre-existing problem must be excluded. In 2014, a revision to the diagnostic criteria for CPSP based on current understanding was proposed by Werner and Kongsgaard.2

Updated Werner and Kongsgaard criteria for diagnosis of chronic post surgical pain 

CPSP: chronic post-surgical pain.


Guidelines and recommendations


Currently, there is no definitive way to prevent the occurrence of CPSP,4 and there is no agreed consensus on the prevention of chronification of acute post-surgical pain (PSP). Preventive strategies may include modification of surgical technique, good pain control throughout the peri-operative period, and pre-operative psychological intervention focusing on psychosocial and cognitive risk factors.4


The International Association for the Study of Pain (IASP) and European Pain Federation (EFIC) recommend three essential strategic components in the management of CPSP: multimodal analgesia, procedure-specific analgesia and acute rehabilitation after surgery.14 Evidence-based guidelines support the use of local anaesthesia and peripheral or neuraxial regional analgesia as important techniques within a multimodal approach.14 Analgesic approaches should also be tailored to the specific surgical procedure as this can impact the type, severity and location of pain.14 However, analgesia is just one dimension of recovery – it alone is often not enough to support full recovery from surgery. Managing CPSP using a multimodal interdisciplinary approach may improve pain control.6

Click here to view the IASP/EFIC fact sheet on current management of post-surgical pain in adults.


Pharmacological treatments


There is some evidence supporting the ability of a preventive, multimodal analgesic regimen to influence the development of CPSP; however, anaesthetic-mediated reduction in the incidence of CPSP has not been confirmed by any large, randomised, prospective trials.13


While morphine or similar opioids have historically been relied upon as the primary treatment to manage PSP, concerns around adverse effects has led to the uptake of multimodal analgesia combining two or more medications with different sites or mechanisms of action.14 This is of particular relevance in PSP as the type of surgical procedure may result in pain arising from different mechanisms (e.g. musculoskeletal pain after orthopaedic surgery; visceral pain after abdominal surgery).14 The advantages of a multimodal pharmacological treatment approach include improved analgesic properties, reduced opioid requirements (opioid sparing) and decreased adverse effects from opioids.14

Where warranted, opioids should only be used in carefully selected patients and prescribed at the lowest dose and shortest duration possible, with well-defined treatment goals and continuous evaluation.15 For further information on the responsible use of opioids, click here.

Systemic analgesics with proven or potential efficacy as components of multimodal analgesia for post surgical pain


Unmet needs

CPSP is a significant clinical problem that seriously impacts post-operative rehabilitation and health-related quality of life. Despite increased research on the pathophysiology of CPSP and recent advances in analgesic therapies, many patients still report severe CPSP.16 An improved understanding of the pathophysiological processes causing the transition from acute to chronic pain is vital to expand the current multimodal approach to include preventive treatments for CPSP.17 The same holds true for treatment of CPSP once it becomes established; management can be inadequate and a greater understanding of how best to both prevent and treat this condition is therefore needed.18



Click here to register for CHANGE PAIN® and access in-depth educational resources on chronic post-surgical pain.


  • References

    1. Gregory P & Settles K. Pract Pain Manag. 2013;13(9):1–6.

    2. Correl D. F1000Res. 2017;6:1054.

    3. Werner MU & Kongsgaard UE. Br J Anaesth. 2014;113(1):1–4.

    4. Thapa P & Euasobhon P. Korean J Pain. 2018;31:155–73.

    5. Macrae WA. Br J Anaesth. 2008;101:77–86.

    6. Richards A. Management of chronic post-surgical pain: an overview. In: Australian Medical Student Journal. 2017. Available at: Accessed June 2020.

    7. Searle RD & Simpson KH. Contin Educ Anaesth Crit Care Pain. 2010;10:12–14.

    8. Bruce J & Quinlan J. Rev Pain. 2011;5:23–9.

    9. Reddi D & Curran N. Postgrad Med J. 2014;90:222–7.

    10. Schug SA et al. Pain. 2019;160(1):45–52.

    11. Weinrib AZ et al. Br J Pain. 2017;11(4):169–77.

    12. Zaslansky R et al. Pain Rep. 2019;4(1):e705.

    13. Kehlet H et al. Lancet. 2006;367(9522):1618–25.

    14. International Association for the Study of Pain (IASP) and European Pain Federation (EFIC). Factsheet: Management of postsurgical pain in adults. 2017. Available at: Accessed June 2020.

    15. Clauw DJ et al. Postgrad Med. 2019;131(3):185–98.

    16. Richebé P et al. Anesthesiology. 2018;129:590–607.

    17. Van de Ven TJ & Hsia HLJ. Curr Opin Crit Care. 2012;18:366–71.

    18. Kleiman AM et al. Reg Anesth Pain Med. 2017;42(6):698–708.