The four-year incidence of CPSP was 4.7% in this study, which is lower than the 17–32% reported in the studies on colorectal surgery [7, 8, 12]. These differences could be explained by the study designs, the time of data collection and the definition of CPSP [5, 7, 8].
We found that age under 55 years, pre-existing chronic pain, a history of previous abdominal surgery, the use of NSAID in the immediate postoperative phase, the use of opioids on discharge, a length of stay over three days and a higher intensity of postoperative pain are independent risk factors for CPSP.
The risk of CPSP is increased in younger patients, as shown consistently before [6, 7, 13]. While female sex was not an independent risk factor in the multivariate analysis, there were significantly more female patients in the CPSP group. Evidence for female or male sex as a risk factor is inconsistent [13]. One possible explanation is mediation of the effect of sex through the effect of the intensity of acute postoperative pain, as shown by Mi et al [14], but in our study those two factors were independent. There was also no correlation between sex and postoperative analgesic drug administration.
Previous abdominal surgery was predicting of CPSP. While studies on patients after colorectal surgery specifically found no difference [7, 8], studies on other abdominal surgeries [6, 15–17] found an association of previous surgery with CPSP. Whether lower individual pain thresholds influenced the indication for previous surgeries and thus the number of surgeries a patient undergoes cannot be evaluated with this analysis. But having had previous surgery was not associated with the level of acute postoperative pain, which suggests that it might be unrelated to the individual pain threshold.
Our study identifies pre-existing chronic pain, both at the site of surgery and elsewhere, as a risk factor for CPSP – this corroborates previous research [15, 18]. Nerve damage during surgery and acute postoperative pain resulting in central sensitization and neuropathic pain syndromes is one of the suspected mechanism of CPSP [6, 17, 19]. A possible explanation for pre-existing chronic pain in addition to previous abdominal surgery as risk factors for CPSP is that the changes in the central nervous system caused by sensitization preceding surgery. This could influence the development of CPSP after the new injury, as could patient-specific decreased pain inhibition mechanisms or preoperative use of analgesics [19, 20].
Consistently with previous research, a higher intensity of acute postoperative pain in the first 24 hours after surgery was identified as a risk factor for CPSP. Liu et al showed that factors associated with acute postoperative pain intensity were anxiety and higher consumption of analgesics [21]. In our study, patients with higher acute pain intensity also had higher in-hospital use of opioids, but psychological factors did not play a significant role. If CPSP is a result of sensitization, then stricter control of acute postoperative pain through adapted analgesic dosage should participate in its prevention.
Multiple interventions to treat acute postoperative pain have been investigated, with various results. In our institution, we consistently use regional anaesthesia techniques in addition to general anaesthesia. TAP blocks are preferred whenever possible, and while they are efficient to reduce acute postoperative pain in the initial phase, they have no effect on preventing CPSP [12, 22, 23]. There was no significant difference between the groups in perioperative pain management, except for the use of NSAID, where it was associated with CPSP, independently from the level of postoperative pain on the NRS. NSAID are not routinely used in our department in the immediate postoperative phase. We tend to prescribe Paracetamol, Metamizol and opioids, adding NSAIDs, Ketamin and/or Clonidine if pain control is insufficient. We found no data on postoperative NSAID use and CPSP in the literature, but the use of at least two combined nonopioid analgesic drug classes during surgery does reduce acute postoperative pain [24]. In our cohort, the level of reported acute postoperative pain was similar in patients who received NSAID in the first 24 hours after surgery and those who did not. NSAID could be a surrogate factor for initially refractory postoperative pain, where additional analgesic drugs did control the postoperative situation, but with no beneficial impact on the risk of CPSP at a later time-point. A recent study suggested that the resolution of acute pain is mediated by an active immune process rather than a progression of acute pain to chronic pain [25]. In patients with chronic pain, this neutrophile-activated inflammatory response would be impaired. Using NSAID or steroids for acute pain, while beneficial in the short-term, would prevent the initiation of an appropriate inflammatory response and thus lead to chronic pain [25]. The use of ketamine has been linked to prevention of CPSP by blocking N-methyl-D-aspartate-receptors and preventing central sensitisation. Its intraoperative use in colorectal surgery led to a lower incidence of CPSP in this population [8, 26], but the effect is not consistent [27] and we did not observe it in our patients, whether for intra- or postoperative use. Dexmedetomidine, a highly selective α2 adrenoreceptor agonist, reduces postoperative pain and opioid use in the acute phase [28]. In a prospective study, it was also associated with significantly less CPSP [29]. In our study, the use of Dexmedetomidine peri- and postoperatively was significantly lower in the CPSP group, but is not significant in the multivariate analysis, which is probably due to the overall low number of patients for which it was used. We do not administer it systematically, and tend to do so in patients with a history of chronic pain or substance abuse.
Patients under Pregabalin at time of surgery seemed to have a lower risk of developing CPSP in this study, for which we did not find a correlation in the literature [27]. A possible explanation for this observed effect in our cohort is that in these patients, pre-existing chronic pain might be better controlled in the preoperative phase. Better preoperative pain control has been linked to lower risk of CPSP in orthopaedic surgery [30]. It might also be that these patients have more frequent follow-up visits in the postoperative phase, be it from a pain specialist, their surgeon or their general practitioner. This would mean that they are more likely to be included in this study, as having follow-up information three months after surgery was an inclusion criterion. The relatively high proportion of patients under Pregabalin in the control group speaks for the quality of the selection, where the control group is not just constituted of otherwise healthy patients.
We found no correlation between depression or anxiety and CPSP. In the literature, there is evidence for psychological factors such as depression, anxiety and catastrophizing as predictors of CPSP [4, 7, 17, 20]. Althaus et al on the other hand found no correlation between anxiety and CPSP in a mixed population of patients who underwent orthopaedic surgery, general surgery, visceral surgery and neurosurgery [31]. VanDenKerkhof et al conducted a prospective study on women who underwent gynaecological surgery, where depression and anxiety were not correlated to CPSP [32]. The importance of these factors could depend on the studied population. More likely, our patients did not undergo a detailed psychological assessment, the presence or absence of psychological comorbidities was taken from the list of diagnosis, which is less precise.
Our study is limited by its retrospective nature. Because we do not systematically see all patients in the outpatient clinic after surgery, 18% percent of all patients who underwent abdominal surgery during this timeframe never had any kind of follow-up visit and had to be excluded. It is also possible that lower intensity pain might not be reported by the patient and/or the physician, and some patients were falsely classified as having no CPSP.
In conclusion, the identification of these risk factors allows for a preventive and personalized health care approach to our at-risk patients. We emphasized the importance of the optimization of pre- and postoperative management, with special attention to sufficient treatment of preexisting chronic pain and acute postoperative pain with a multimodal analgesic approach. Finally, an additional follow-up consultation 3 months after surgery should be considered in at-risk patients, to avoid a delay in diagnosing CPSP and uncontrolled and inadequate long-term opioid use.