Bariatric Surgery May Reduce Central Pain Sensitization

Janis C. Kelly

January 26, 2018

Bariatric surgery was associated with significant reductions in knee pain in obese patients, as well as with reductions in pain sensitivity at the wrist. These findings suggest that changes in central pain sensitization occurred in these patients, who lost an average 29.0% of their baseline body weight.

Joshua J. Stefanik, MSPT, PhD, from Department of Physical Therapy, Movement and Rehabilitation Sciences, Northeastern University, Boston, Massachusetts, and colleagues reported this discovery online January 5 in Arthritis Care & Research.

"This paper adds to the literature of improvements in comorbidities with bariatric surgery," coauthor Caroline M. Apovian, MD, told Medscape Medical News. "Rheumatologists and other specialists, cardiologists, [primary care providers,] etc., should recommend bariatric surgery for their patients with [body mass index (BMI)] over 40 or over 35 with comorbidities for a myriad of reasons. One is the pain resulting from arthritis. Bariatric surgery is the only treatment for severe obesity that is effective enough to achieve a 32% weight loss which is sustained long term." Dr Apovian is director, nutrition and weight management, and professor of medicine and pediatrics, Boston Medical Center, Massachusetts.

To learn whether pain reduction after bariatric surgery was primarily a result of reduced mechanical loading or also of changes in peripheral and/or central sensitization, the investigators compared outcomes for obese persons with knee pain undergoing bariatric surgery with those of similar patients undergoing medical management for obesity. The authors hypothesized that if pain relief was a result of mechanical changes, it would only occur in affected joints (knee pain, in this study). In contrast, if central pain sensitization changed, then one might expect to see reduced pain levels in other areas.

The researchers recruited 67 subjects with knee pain from the Nutrition and Weight Management Center at Boston Medical Center. All had a BMI of 35 kg/m2 or more with a weight-related comorbidity, or more than 40 kg/m2 with no weight-related comorbidity. Exclusion criteria included prior knee surgery or inflammatory arthritis. In this nonrandomized study, 45 patients had bariatric surgery (either laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy), and 22 had medical management (high-protein, low-fat diet of 1200 - 1500 kcal/day for women and 1500 - 1800 kcal/day for men plus exercise prescriptions with or without medications including phentermine, lorcaserin, phentermine/topiramate, bupropion/naltrexone, or liraglutide).

Pain and pain sensitization were assessed at baseline and 12 months later, using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Frequent pain was defined as pain, aching, or stiffness on most days in the last 30 days and was assessed at 19 sites outside the knees, using a body homunculus. Mechanical pain sensitivity was assessed as the pressure pain threshold (PPT), using a handheld algometer applied at the center of the patella of the most painful knee. As a control site, the algometer was applied to the right wrist, a site not typically affected by osteoarthritis.

At 12 months, the researchers found that mean weight loss was 32.7 kg (29.0%) in the surgery group and 4.6 kg (4.1%) in the medical management group.

Mean WOMAC scores decreased by 4.9 points in the surgery group (P < .0001), but did not change significantly in the medical management group. The authors note that many comorbidities of obesity improve with a 5% to 10% weight loss, which suggests that the 4.1% loss in the medical management patients was likely too low to improve pain sensitization.

Pain tolerance at the patella increased significantly in the surgery patients (PPT +133.3; P = .0007), but did not change significantly in the medical management patients.

Unexpectedly, pain tolerance in the wrist also increased significantly among the surgery patients (PPT +103.8; P = .005), but not in the medical management group.

"I think that changes in the wrist PPT as well as in the patellar PPT suggest that central sensitization was altered as well as peripheral sensitization," Dr Apovian explained.

Change in weight correlated with changes in WOMAC pain and patella PPT, but not with change in wrist PPT.

Dr Apovian said, "Changes in weight not correlating with wrist PPT suggest that the central mechanism is not weight related and perhaps related to a hormone change or genetic differences in response to bariatric surgery. Perhaps the changes in inflammation take longer in some to resolve, or perhaps they do not resolve such as what we see in type 2 diabetes mellitus. The surprise for us was that pain is not just weight based and that there is much more to investigate, both with inflammation and with hormone changes, that may act centrally to affect the feeling of pain."

IL-10 May Mediate Pain Sensitization

In a related study, published in the Journal of Pain, Andrew Schrepf, PhD, and colleagues from the University of Michigan, Ann Arbor, found that interleukin 10 (IL-10) might be one of the mediators that link weight loss to pain relief.

Dr Schrepf's group studied whether weight loss using a low-calorie diet would improve pain, affect, and somatic symptoms associated with chronic pain. They conducted an observational study in 123 obese individuals undergoing a 12- to 16-week intervention using a very low calorie diet (800 kcal/day) in the form of total liquid meal replacement, with the goal of 15% weight loss from the baseline weight. Participants lost an average 16.05% of baseline weight, and 80% of patients lost at least 10% of baseline body weight.

To assess somatic symptoms and widespread pain, the team used the American College of Rheumatology criteria for fibromyalgia, which they say has proven useful in measuring "persistent pain and analgesic nonresponsiveness" in other settings. They found that American College of Rheumatology score decreased from 6.42 at baseline to 5.42 after weight loss (P = .004). Weight loss was also associated with significant improvements in symptom severity (fatigue, sleep difficulties) and depression. Weight loss was associated with an approximately 20% decrease in probability of reporting pain at any site on the body map, and greatest decreases were in the lower legs, lower back, chest, and jaw.

Dr Schrepf and colleagues measured inflammatory markers in a subset of 31 patients at baseline and after weight loss and found significant increases in levels of IL-10 and in the ratio of IL-10 to IL-6 and C-reactive protein, "suggesting an increase in anti-inflammatory tone after caloric restriction," the authors write.

The researchers conclude that weight loss associated with a low-calorie diet was associated with improvements in 2 hallmarks of complex chronic pain conditions: the spatial distribution of pain, and somatic symptoms.

They comment, "These results appear to be the serendipitous result of weight loss, because the participants were not seeking treatment for pain/somatic symptoms." Furthermore, subjects who lost more than 10% bodyweight showed greater improvement in depression, pain, and total modified ACR scores.

Weight loss was associated with increases in IL-10 levels, but these increases did not correlate with the magnitude of changes in symptoms. The authors write, "Additional assessments of inflammatory activity to determine if shifts in inflammatory tone precede symptom improvement or simply parallel them are needed."

Dr Apovian reports grants and/or personal fees from Amylin, Nutrisystem, Zafgen, Sanofi-Aventis, Orexigen, Novo Nordisk, Aspire Bariatrics, GI Dynamics, Myos, Takeda, Scientific Intake, Gelesis, Science-Smart LLC, Merck, and Johnson & Johnson, and grants from the Vela Foundation and from the Dr Robert C. and Veronica Atkins Foundation outside the submitted work. Several co-authors on Dr Schrepf's study report research funding or consulting fees from Aptinyx, Cerephex, Forest Laboratories, Eli Lily, Merck, Pfizer, Analgesic Solutions, Aptinyx, deCode Genetics, Cerephex, Tonix, Theravance, Abbott, UCB, Johnson & Johnson, and Purdue Pharma.

Arthritis Care Res. Published online January 5, 2018. Abstract

J Pain. 2017;18:1542-1550. Abstract

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