Genetics of chronic post-surgical pain: a crucial step toward personal pain medicine

Abstract

Purpose Most patients who undergo surgery or experience a traumatic injury suffer from acute pain that subsides once tissues heal. Nevertheless, the pain remains in 15-30% of patients, sometimes for life, and this chronic post-surgical pain (CPSP) can result in suffering, depression, anxiety, sleep disturbance, physical incapacitation, and an economic burden. The incorporation of genetic knowledge is expected to lead to the development of more effective means to prevent and manage CPSP using tools of personalized pain medicine. The purpose of this review article is to provide an update on the current state of CPSP genetics and its future potential.Principle findings The large variability in CPSP amongst patients undergoing similar surgery suggests that individual factors are significant contributors to CPSP, raising the possibility that CPSP is influenced by genetic determinants. Heritability estimates suggest that about half of the variance in CPSP levels is attributable to genetic variation. These estimates suggest that identifying the genetic underpinnings of CPSP may lead to significant improvements in treatment. Analyzing patients' DNA sequences, blood and salivary pain biomarkers, as well as their analgesic responses to medications will facilitate developing insights into CPSP pathophysiology and inform predictive algorithms to determine a patient's likelihood of developing CPSP even prior to surgery. These algorithms could facilitate effective treatment regimens that will protect against the transition to chronicity in traumatically injured patients or those scheduled for surgery and lead to better therapy for patients who have already developed CPSP.Author contributions Hance Clarke, Joel Katz, Herta Flor, Marcella Rietschel, and Scott Diehl are co-authors of the manuscript and are responsible for revising some of the manuscript. Ze'ev Seltzer is the lead author responsible for revising the manuscript.

Interfascial Plane Blocks

“…Experts currently suggest that aggressive treatment of acute pain may have potential benefits in preventing the transition to persistent postsurgical pain. [30][31][32] …”

Transitional Pain Medicine: novel pharmacological treatments for the management of moderate to severe postsurgical pain

“…[8] Although significant advances in pain genetics are more than 5 years away, it is hoped that a worldwide consortium focused on studying chronic postsurgical pain and collecting the DNA of patients that transition to chronic postsurgical pain will lead to the development of novel therapeutics to improve the treatment of CPSP and other chronic neuropathic pain conditions. [35] CPSP can result from essential, life-saving surgery and it would never be suggested that surgery not be performed in these situations. However, acceptance and acknowledgment by surgical teams that CPSP is a potential consequence of surgical intervention are of upmost importance.…”

Preventive Analgesia and Novel Strategies for the Prevention of Chronic Post-Surgical Pain

“…Recent reviews in pain genetics estimate that chronic pain heritability ranges from 30 to 70 % [78]. Presently it is not possible to ascertain the extent to which individual genetic factors contribute to a person's propensity to develop chronic postsurgical pain or their response to therapy [79]. A number of candidate genes have been identified for chronic pain, including a few for post-surgical and posttraumatic pain.…”

“…A number of candidate genes have been identified for chronic pain, including a few for post-surgical and posttraumatic pain. These include genes encoding for ion channels, neurotransmitter enzymes, receptors, transporters, transcription factors, and hormone receptors that increase the risk for pain chronicity [79]. While there are numerous studies that are ongoing, variations of three genes mapped in rodent models have been associated with chronic pain in humans.…”

“…The ultimate goal of pain genetics is to enable clinicians to predict preoperatively who is at risk of developing CPSP and translate this understanding into pharmacologic and surgical decisionmaking. Improved knowledge could contribute to personalized preventive pain treatments and allow management to move away from the current symptom-based approach [79].…”