Chronic Postsurgical Pain

It is alarming that chronic postsurgical pain (CPSP) has assumed an epidemic proportion and deserves greater attention as the number of procedures being performed annually increases in the world. The consequence of CPSP can vary from mild to severe loss of quality of life. The first publication that identified surgery as a risk factor for CPSP appeared in 1998.1 This finding led to a dramatic increase in interest on this subject; searches on PubMed now reveal hundreds of publications on this topic. Although there are several publications on this emerging topic, the lack of a clear definition of CPSP makes comparisons of different studies and truly estimating the incidence of CPSP difficult. As an initial step, it is critical that a definition of CPSP based on scientific facts be formulated. Currently, it is accepted that CPSP should at least be of 2 months' duration2 after the surgical insult, which is an empirical time frame. Before a diagnosis of CPSP can be made, all other possible etiology for the postsurgical pain needs to be excluded. In addition, future CPSP trials should define in detail the location, characteristic, and consequence from CPSP on physical and social function.3 Kehlet et al. in 20064 outlined 3 possible mechanisms and pathophysiology for CPSP: a continuing inflammatory response; neuropathic pain; or predisposition to CPSP due to the patient's genetic makeup. If it is the latter, and the specific genetic determinant can be identified, patients undergoing elective surgery can be informed of the risk of CPSP. To achieve this, large clinical trials need to be performed to identify the genetic profile of patients predisposed to developing CPSP. In 2010 the Food and Drug Administration formed a panel called ACTION (Analgesic Clinical Trial Innovations, Opportunities and Network) and challenged the scientific community to develop preventive strategies for CPSP.5 Preoperative pain and6 psychological traits such as catastrophizing7 have recently been determined to be predictors of CPSP. Increased postoperative pain has also been suggested as an independent risk factor for CPSP. With regard to postoperative pain, differentiation between causality and association is exigent. It may well be that patients with severe acute postoperative pain experience greater spinal cord sensitization and therefore develop more persistent postsurgical pain. On the other hand, it may be postulated that patients with precursors of persistent postsurgical pain have severe acute postoperative pain because they are already developing CPSP. If CPSP is due to a continuing inflammatory process or is neuropathic, preventive measures could possibly be undertaken. The perioperative physicians (anesthesiologists) need to be in the leadership role to understand and institute measures to prevent CPSP. The incidence of neuropathic pain after total knee arthroplasty was determined to be 6%8 in a recent study. This is very similar to the value of 5.2% (control group) in a randomized controlled study examining the role of pregabalin for prevention of neuropathic pain (CPSP) after total knee arthroplasty published in 2010 with detailed examination.9 Similarly, estimates of neuropathic pain for different surgical procedures are 28% for thyroid surgery,10 19% for mastectomy,11 29% for thoracotomy,12 and 6% for hernia repair.13 One of the possible reasons for the wide variation in incidence of neuropathic pain after surgery may be due to the diagnostic test or questionnaires used in their studies. Future clinical trials need to only use validated neuropathic pain scales and standard diagnostic tests.14 The first line of therapy for neuropathic pain is gabapentenoids (α2δ ligand, voltage-dependent calcium channel inhibitors).15 Gabapentenoids have been used as an adjunct for acute postoperative analgesia and meta-analyses have demonstrated that they reduced opioid consumption and improved pain scores.16,17 A detailed systematic review and meta-analysis on the use of gabapentin and pregabalin for the prevention of CPSP was performed by Clarke et al.18 Of 567 clinical trials screened, 11 studies met the criteria for CPSP and Delphi criteria for quality assessment. Of the 11 studies, 8 used gabapentin and among them those demonstrating a reduction in CPSP involved larger preoperative doses (1200 mg of gabapentin) and a continuation of pharmacological therapy into the postoperative phase. Similarly, the 3 pregabalin studies that demonstrated a reduction in CPSP used a relatively large dose of 300 mg and continued this into the postoperative phase. Though there are no large scale equivalent analgesic dose conversion studies between gabapentin and pregabalin, some early studies equate 900 to 1500 mg of gabapentin to about 225 mg of pregabalin and 1500 to 2100 mg of gabapentin to about 300 of pregabalin.19 Given the mechanism of action of these 2 drugs, there is no doubt that multiple administrations of either drug are required to effectively reduce the neuropathic pain of CPSP. There is no doubt that further large-scale, long-term outcome clinical prospective trials need to be performed in the field of CPSP and gabapentenoids. Clarke et al.'s18 systematic review and meta-analysis should motivate further research to determine the optimal dose and duration of therapy of gabapentin and pregabalin to prevent CPSP. However, because both drugs have adverse effects, it is not prudent to use them universally for all surgical patients. There is a need to develop a screening tool or diagnostic test that can preoperatively identify those patients most likely to develop neuropathic CPSP to warrant administration of gabapentin or pregabalin or other drugs. In the current health economy, the administration of drugs to patients is always warranted when supported by outcome data. It is critical to appreciate that the cost of treatment and loss of quality of life and impact20 due to neuropathic pain in a few patients outweighs the cost of therapy for prevention currently to all high-risk surgical patients, until improved diagnostic screening tools are available. Gabapentinoids are the first drugs to show promise in combating CPSP. Future research is needed to identify other methods, in addition to drugs, to combat this silent epidemic of CPSP. DISCLOSURES Name: Asokumar Buvanendran, MD. Contribution: This author wrote the manuscript. Conflicts of Interest: This author has no conflicts of interest to declare. This manuscript was handled by: Spencer S. Liu, MD.