Chapter 5
Identification of risk and protective factors in the transition from acute to chronic post surgical pain

Joel Katz^1,2,3, M. Gabrielle Pagé^4,5, Aliza Weinrib², & Hance Clarke^2,3

¹ Department of Psychology, York University, Toronto, Canada

² Department of Anesthesia and Pain Management, Toronto General Hospital, Toronto, Canada

³ Department of Anesthesia and Pain Medicine, University of Toronto, Toronto, Canada

⁴ Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montréal, Canada

⁵ Département d’anesthésiologie et de medicine de la douleur, Faculté de médecine, et Département de Psychologie, Faculté des arts et des sciences, Université de Montréal, Montréal, Canada

Introduction

Every chronic pain was once acute. Yet not all acute pain becomes chronic. Some pains develop spontaneously. Others arise as the result of surgery, accident, or illness. Regardless of the cause, most people recover and do not develop persistent pain. Nevertheless, there is obvious interest in determining the factors responsible for the transition of acute, time‐limited pain to chronic, intractable, pathological pain [1]. Identification of causal risk factors is the first step in developing effective treatments to prevent and manage pain. In this chapter we focus on the transition of acute to chronic pain after surgery. For several reasons, the study of pain after surgery can serve as a model for the transition to chronicity for other types of pain: (1) Chronic postsurgical pain (CPSP) develops in an alarming proportion of patients; (2) Research into the transition from acute to chronic pain has already revealed specific risk factors that predict who develops CPSP (3); Elective surgery is unique in that the timing and nature of the physical injury are known in advance. This facilitates identification of risk and protective factors that predict the course of recovery; (4) There is a growing body of literature examining preventive efforts to minimize the development of CPSP.

The aim of this chapter is to provide a selective overview of CPSP. We review the basic epidemiology of CPSP according to surgery type; define the concept of a risk factor and the requirements for determining causality; describe the surgical, psychosocial, social‐environmental, and patient‐related factors that confer a greater risk of developing CPSP; review the rationale and evidence for a preventive analgesic approach to surgery designed to reduce the incidence and intensity of CPSP; and describe preliminary outcomes from a multi‐professional Transitional Pain Service specifically designed to prevent the transition from acute to chronic pain after surgery.

Definition and Epidemiology of CPSP

The most recent revision of the International Classification of Diseases (ICD‐11) defines chronic postsurgical pain (CPSP) as pain that [1] develops or increases in intensity after a surgical procedure, [2] has been present for at least 3 months (i.e., persists beyond the typical healing time), [3] is localized to the surgical field or projected/referred to a dermatome or deeper structures subserved by involved nerves, and [4] is not caused by other factors (e.g., pre‐existing pain, infection, cancer recurrence) [2]. Some authors have suggested the additional criterion, not currently part of the ICD‐11 definition, that CPSP must interfere substantially with everyday activities [3]. ICD‐11 sub diagnoses include CPSP after amputation, arthroplasty, breast surgery, herniotomy, hysterectomy, spinal surgery and thoracotomy, although other surgical procedures also result in CPSP.

Although most patients who undergo major surgery do not develop CPSP, the incidence of CPSP following certain surgical procedures is unacceptably high [2 4–6] (Table 5.1). The one‐year incidence of CPSP is variable and surgery‐specific, ranging from upwards of approximately 30% after modified radical mastectomy and hysterectomy to more than 50% after joint arthroplasty, hernia repair, spinal surgery and thoracotomy and almost 80% for limb amputation. Across surgery types, the one‐year CPSP incidence of moderate‐to‐severe pain has been estimated to be between 8% and 39% [6]. We know next to nothing about CPSP beyond the one‐year mark: Pain persists in 8.1% ‐ 19% of patients up to 6 years after hernia repair with severe or very severe pain occurring in 1.8%. Two years after amputation, approximately 60% and between 21%‐57% of amputees report phantom limb pain and stump pain, respectively. These statistics are alarming considering the total number of patients worldwide who undergo surgery each year. That almost 25% of patients referred to chronic pain treatment centers have CPSP reflects the intractability of the problem.

Table 5.1 Incidence of chronic postsurgical pain (CPSP) after various surgical procedures

Surgical Procedure	Incidence of CPSP	Follow‐up Time after Surgery
Amputation	59‐79%	1‐2 years
Arthroplasty	13‐65%	12 months
Breast surgery	13‐33%	12 months
Herniotomy	19‐57%	1‐5 years
Hysterectomy	21‐28%	12 months
Spinal surgery	56%	12 months
Thoracic surgery	41‐51%	1‐1.5 years

Data from the following sources: Schug et al. [2]; Katz & Seltzer [4] Fletcher et al. [6]

Understanding Risk and Attributing Causality to Outcomes

An important goal of epidemiological and clinical research is to identify the necessary and sufficient conditions under which specific health‐related outcomes arise. This typically is achieved over the course of many years involving progressively more sophisticated research designs from observation and description through to experimental manipulation. Initially, an understanding is developed through careful observation of the conditions under which the phenomenon occurs. The next stage involves prediction; specifying in advance the situations under which the phenomenon occurs and the factors that reliably predict its occurrence. The final stage involves prevention and control, which requires detailed knowledge of the causal mechanisms that give rise to the phenomenon and specialized tools to facilitate or inhibit its occurrence. In the field of CPSP, the process of moving from understanding through prediction to control is linked to the concept of risk and to accurately identifying the (risk and protective) factors that place an individual at greater or lesser likelihood of developing CPSP.

A risk factor is defined as a “measurable characterization of each subject in a specified population that precedes the outcome of interest and can be used to divide the population into … high‐risk and … low‐risk groups …” [7]. Merely identifying a risk factor however does not provide information about risk estimation, and this is particularly relevant for studies with large sample sizes. Risk estimation should always be based on the relative potency of a risk factor. Tools to evaluate the potency of a risk factor include odds ratio, risk ratio, and Cramer’s V [8].

A relevant and often overlooked issue pertinent to the concept of risk is that of correlation versus causality, necessitating a distinction between the terms causal risk factor and correlated risk factor [7]. As described above, to meet the requirements for a risk factor, the observed variable must precede the outcome of interest. If the factor is measured at the same time as, or after, the outcome, then it may be a symptom or consequence of the outcome. When the temporal criterion of precedence is not met, as for example in a cross‐sectional study, the observed variable is simply a correlate of the measured outcome. Moreover, the temporal criterion of precedence is necessary, but not sufficient, to infer causality. Thus, even if a risk factor is shown to precede the development of the outcome, it does not imply causality and may be a correlate. A risk/protective factor is determined to be causal if its manipulation increases/decreases the risk associated with the measured outcome [7]. Determining the status of a given risk factor as causal or non‐causal is essential to progress in understanding the development of CPSP and in prevention and treatment efforts; attempts to manipulate a non‐causal risk factor (i.e., a correlate) will have no effect on the outcome (see Figure 5.1E). A major objective of epidemiological research is to identify causal, modifiable risk factors. Demonstrating the causal role of specific risk factors for CPSP is time‐consuming, expensive, and requires an evidence base of many randomized, controlled trials. Figure 5.2 shows a schematic illustration of the risk and protective factors involved in the transition to CPSP and disability and how they interact across the pre‐operative, intra‐operative, and post‐operative phases of the peri‐operative period.

The increased availability of large datasets and continuously evolving computational approaches, such as machine learning, has also introduced new methodologies to build prediction models [9]. While often such models make it difficult to pinpoint specific risk factors that could become the target of preventive measures, they are becoming increasingly precise in predicting presence or absence of CPSP [10].

Factors Associated with CPSP

Surgical Factors

The following surgical factors are associated with a greater risk of developing CPSP: increased duration of surgery, low (vs high) volume surgical unit, open (vs laparoscopic) approach, peri‐costal (vs intracostal) stitches for thoracotomy, conventional hernia repair and intraoperative nerve damage [4]. Whether the above factors are causally related to the development of CPSP is not yet known. However, these factors appear to be associated with greater surgical trauma, and, in particular, they point to intraoperative nerve injury as a likely causal mechanism and the main culprit in producing both acute and chronic neuropathic pain. Thus, one useful preventive measure that can be taken is to avoid intraoperative nerve damage. This is not possible for certain surgeries such as limb amputation that involve ligation and section of major nerve trunks. However, the practice of intentionally transecting nerves for surgical convenience can be avoided and doing so will reduce the incidence of CPSP.