Predicting Postop Shoulder Pain
Chronic postsurgical pain (CPSP) is a pervasive problem. It affects up to 50% of patients and, unfortunately, it can be hard to predict.1,2 Chronic preoperative pain, acute postsurgical pain, comorbid stress symptoms—all of these could contribute to CPSP.1 Yet today’s predictive models may be incomplete, leaving out psychological and genetic factors that could help predict (and minimize) a patient’s pain experience.
Researchers at the University of Florida have been researching a new patient subgroup with certain biopsychosocial characteristics that have shown heightened pain responses to exercise-induced shoulder injury (EISI).3-5 This subgroup has a high prevalence of catastrophizing behavior and share a genetic characteristic: low enzymatic activity of catechol-O-methlytransferase (COMP), a genotype well known to be a modulator of pain experience.6
According to lead author of the study Steven Z. George, PT, PhD, an associate professor at UF’s Department of Physical Therapy, incorporating more precision medicine into predictive models will take time, though, as electronic medical records improve data collection and genetic research continues to investigate the role DNA plays with chronic pain.
“We are starting to see convergence on key factors that may help predict outcomes,” Dr. George said in an email interview. “Since some of the more established factors are not genetic, the first generation of these models will be built with other predictors, like the psychological factor used in our study [pain catastrophizing].”
How the Study Was Performed
The researchers evaluated 150 shoulder arthroscopy patients, assessing Pain Catastrophizing Scale scores, Fear of Pain Questionnaire responses, and genetic data of various pain modulating and pro-inflammatory genes, which was extracted from buccal epithelial cells. Brief Pain Inventory measurements were made 3, 6, and 12 months after the surgery by research assistants blinded to the patients’ subgroup status.
By also taking into account possible co-founders, like comorbid depressive symptoms, medication status, and the size of the tear to the rotator cuff, the researchers used robust analysis to see if those same heightened pain responses found in the EISI patients translated to worsened clinical outcomes with postoperative shoulder pain (POSP). The full study was published in Pain .7
Patients in the COMT and catastrophizing subgroup had higher pain intensity ratings at 3 and 6 months following the surgery, and were half as likely to make a normal recovery after 12 months (P=0.002). The results held up against sensitivity analysis and potential confounders.
The genetic and psychological parameters were a strong predictor of the group’s POSP outcomes, which suggests predictive models could soon be incorporating more psychological and genetic factors to help spot patients susceptible to chronic pain, especially after a musculoskeletal surgery.
Evolving Pain Prevention
Catastrophizing behavior can affect a patient’s pain intensity8 and recovery process9 and contribute to the incidence of chronic pain.10,11 One recent study found that a parent’s catastrophizing behavior even could affect the outcome of their child’s postoperative pain.
“As these models and their performance become established, they provide the foundation for adding other information (eg, genetics) to see how much the accuracy improves (or if the accuracy improves),” Dr. George said.
Approximately 50% of the risk of developing chronic pain is determined by genetic factors.6 COMT, being the most commonly associated with chronic musculoskeletal pain conditions, is one genotype that researchers believe has significant impact on the body’s pain modulatory processes.
It’s a detoxifying enzyme integral to adrenergic pathways, catabolizing various catechol neurotransmitters, like epinephrine, norepinephrine, and dopamine. Variations of this gene, such as COMT single-nucleotide polymorphism rs6269, could mitigate its enzymatic activity, therefore heightening pain response.7
“I think that in the future this information is going to be provided by patients who have done the genotyping on their own. I think that will happen before genotyping is ordered routinely by health care providers. Then the provider’s job becomes one of interpreting the genetic data provided and factoring it into overall risk determination,” Dr. George said.
Looking Ahead to Targeted Therapy
Some institutions already are exploring how genetic data could be used in the clinical setting. Beth Darnall, PhD, a clinical associate professor at Stanford University School of Medicine in Palo Alto, California, said they are collecting samples for genetic testing and planning to use the data to develop their own personalized medicinal approaches “to deliver targeted therapies at point of care.”
As for this new COMT and catastrophizing patient subgroup, there is still much to learn. The pathophysiological mechanisms of COMT possibly present a novel biologic pathway for pharmacological treatment, which already is being explored with propranolol, a nonselective β-adrenergic antagonist typically used to treat hypertension.12
There is also potential to see if COMT rs6269 and catastrophizing’s effects replicate to other anatomical sites of musculoskeletal pain (back, neck, knee, etc.)—or whether the combined effects of catastrophizing and COMT interact at a neurobiological level, Dr. George and collegues noted.
But for now, Dr. George said he and his team want to see if the subgroup’s outcomes can be improved through various treatments. “Our planned follow up study will investigate whether pharmacological and behavioral treatment targeted to the COMT and pain catastrophizing subgroup will result in improved pain outcomes. This investigation will start in a pre-clinical model involving healthy human subjects that experience induced shoulder pain. It is our hope that such a pre-clinical study will provide the guidance needed to test in a clinical trial.”
The study reported in Pain was funded by the National Institutes of Health. The authors declared no conflicts of interest.