The presence of acute pain following surgical procedures is a prominent healthcare concern, and its impact on postoperative recovery and outcomes is widely acknowledged.1 Its significance led to numerous research efforts aimed at enhancing its treatment. The understanding of the pathophysiology behind postoperative pain has greatly improved over the last 30 years, leading to a more advanced and sophisticated management of acute pain after surgery.2 Similarly, emphasising the development of procedure-specific recommendations for managing perioperative pain has pushed the field of perioperative pain management forward (https://esraeurope.org/prospect/). However, there remain numerous unanswered questions about the most effective approach to perioperative pain management, particularly for patients who experience more intense pain postsurgery than the average patient. There are multiple areas that can be further developed, including the optimisation of pain management to strike a balance between effectiveness and potential side effects, particularly when opioids are required. It is also important to identify the most effective combination of treatment options and explore nonmedical approaches to pain relief. Furthermore, it is crucial to thoroughly investigate the effects of opioid-free anaesthesia on postoperative pain, along with various other associated fields. However, what has been overlooked in recent years is the significant number of patients who continue to experience pain for weeks, months and even years after surgery. This unexpected phenomenon challenges the previous belief that postoperative pain is a temporary symptom that will eventually fade away.

In 2006, an article was published in the Lancet by Kehlet et al.,3 highlighting the significant and often overlooked issue of persistent postsurgical pain (CPSP). They characterised the risk as about 10 to 50% of patients developing CPSP after common surgical procedures, with 2 to 10% experiencing rather severe pain even years after the surgery. The community, including clinical researchers, took great notice of this matter. In the subsequent years, several observational trials, albeit mostly of limited scope, provided support for these incidence rates. Notably, some trials even indicated higher rates, particularly in the context of specific surgical procedures. Interestingly, there was significant variation in the incidence rates following the same surgical procedures across various studies.4 Differences in the outcome criteria used to define CPSP are one of the reasons for the discrepancy in study results. For instance, while some studies defined CPSP as any type of pain, others used a pain intensity rating higher than 2 on a 10-point Numeric Rating Scale (NRS) as a cutoff off. In some studies, severe pain or moderate-to-severe pain were the criteria, whereas others did not provide a specific definition of the outcome. This has already posed challenges in comparing study findings. Similarly, time points of assessment including primary endpoints differed widely between studies without clear cutoffs. Additionally, the remaining criteria, such as preoperative pain levels or the use of analgesic medications, either exhibited discrepancies or lacked comprehensive descriptions. As well as surgical procedures varying significantly, the studies lacked consistency, making it difficult to draw definitive conclusions. Consequently, the exact prevalence of CPSP remains unknown to date.

A major challenge in CPSP studies is the absence of a widely accepted and standardised definition. CPSP lacks sufficient coding in the 10th version of the International Classification of Diseases (ICD-10) coding system of WHO, and this hinders the collection of precise epidemiological data regarding chronic pain. This all has changed recently. In 2019, a task force of the International Association for the Study of Pain (IASP) provided a distinct definition of CPSP.5 In conjunction with the WHO, this task force devised a definition for chronic pain and a corresponding coding system to be integrated into the updated ICD-10. The inclusion of CPSP in the ICD-11 coding system is a crucial advancement in defining and acknowledging CPSP as a secondary pain condition. In general, chronic pain refers to pain that persists or recurs for more than 3 months.6 The generalisation of this definition is facilitated by its clear, albeit artificial, emphasis on pain duration. Pain experienced after surgery, particularly at the 1 to 2 months mark, is considered a prolonged and significant factor in the development of CPSP. According to the CPSP definition, pain is not considered chronic until it lasts for over 3 months. Additionally, there are other relevant criteria to consider before classifying postsurgical pain as ‘chronic’ for CPSP5 (compare Table 1).

Table 1 - The ICD-11 definitions of chronic postsurgical pain 1. Pain that develops or increases in intensity after a surgical procedure or a tissue injury and persists beyond the healing process, that is, at least 3 months after the initiating event. 2. The pain has to be localised to the surgical field or area of injury, projected to the innervation territory of a nerve situated in this area, or referred to a dermatome or head zone (after surgery/injury to deep somatic or visceral tissues). 3. Other causes of pain such as preexisting pain conditions or infections, or malignancy, and so forth, have to be excluded in all cases of chronic posttraumatic and postsurgical pain. Data from Schug et al., 2019.5

In 2019, the World Health Assembly gave its endorsement to ICD11 and, in 2024, the last version of the ICD was integrated in the European Health Data Space regulations. Starting from these specific dates, health statistics can be documented using the ICD-11 system. Therefore, any future studies should use the CPSP definition to ensure comparability in future trials. This is relevant not just to studies that focus on the epidemiology of CPSP. There are two pressing matters related to CPSP: accurately identifying patients with a high risk of developing it, and implementing effective prevention strategies.7 Both these issues remain unsolved. The accuracy and validation of all existing clinical prediction prognostic models are questionable, as they are highly susceptible to bias and lack reliability.8,9 The currently available treatment strategies, such as drugs administered during the perioperative period or over a longer duration, do not appear to offer adequate prevention.10 The implementation of the new ICD-11 coding system, alongside the standardised definition for CPSP, will facilitate the alignment of primary endpoints in clinical trials to effectively address these emerging issues.

In addition, there are significant unresolved issues that need to be addressed and coordinated. One important fact to consider is that chronic pain, regardless of its type, is recognised as a biopsychosocial disease, and, in some cases, a disease in its own right11 Therefore, if pain persists over time, it significantly impacts on both physical and psychological functioning. In order to adequately evaluate chronic pain, it is imperative to address these aspects, at the very least the most important ones. Once again, it is crucial to ensure consistency across studies, allowing for meaningful comparisons between different trials, and making sure that they are relevant and understandable to patients, and all stakeholders involved in their treatment. To ensure consistency in outcome assessment across pain-related studies, NIH and IMI-PainCare collaborated on the development of overarching Core Outcome Sets (COS)s for those aspects (domains and subdomains) to be assessed in all trials of a certain pain category.12 ‘Chronic pain’ was one pain category, and the ‘transition from acute to chronic pain’ was another; the domains for these two categories are shown in Table 2. Consequently, it is crucial to include these domains as core areas in all future trials, allowing for the assessment of not only pain intensity but also other aspects related to pain. Repeatedly conducting such assessments in studies focused on CPSP would facilitate the comparison of results, particularly in relation to the epidemiology, prediction and prevention of CPSP (Fig. 1).

Table 2 - Final core outcome sets of domains for two pain categories, acute pain and chronic pain Acute pain Chronic pain Domains in the COS Pain Pain intensity Pain Pain intensity Pain interference Pain interference Physical function Activities of daily living Quality of life Quality of life Additional domains to be considered Analgesic use Physical function Psychological functioning Quality of life: physical Data from Bova et al., 2023.12 These COS were developed with expert stakeholders across a range of disciplines, countries, and backgrounds, and uniquely included equal participation of people with lived experience (PWLE). These COS can improve harmonisation of data assessment in clinical trials and allow for future comparisons of results across trials related to acute pain and chronic pain.
Fig. 1:

Progress in research on chronic postsurgical pain.

In conclusion, the adoption of the ICD-11 coding system and standardised definitions for CPSP heralds a pivotal advance. These breakthroughs acknowledge the intricate biopsychosocial nature of CPSP and will improve the comparability of research. With a growing emphasis on improving prediction models and creating advanced prevention strategies for CPSP, there is promise of a chance to improve the quality of life for individuals affected by CPSP. This marks the beginning of a new era in which pain management and patient care can be more effective.

Acknowledgements relating to this article

Assistance with the article: none.

Financial support and sponsorship: none.

Authors’ contribution (CRediT Taxonomy): conceptualization: EMPZ; methodology: EMPZ, PF; writing – original draft: EMPZ; writing – review and editing: EMPZ, PF; approving the final version, reading and confirming meeting the ICMJE criteria for authorship: EMPZ, PF.

Conflicts of interest: EPZ received speaker's fees from Grunenthal, Medtronic and Novartis; all went to the institution EPZ is working for. PF received advisory board/speaker fees from Grunenthal, Oncomfort and GE Healthcare.

This manuscript was handled by Charles Marc Samama.

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