Postbariatric Surgery Chronic and Neuropathic Pain

Obesity has reached epidemic proportions in New Zealand with the third highest rate in the OECD. Musculoskeletal physicians are seeing an increasing number of patients with a history of bariatric surgery. Bariatric surgery can be life-saving, with dramatic reductions in obesity-related complications such as cancer rates, diabetes, and cardiovascular disease. However, there is an overall increased prevalence in the long-term of chronic pain and psychiatric disease. (see also Obesity and Chronic Pain). 
A systematic review and meta-analysis by Aghili et al. highlighted that while bariatric surgery can improve neuropathic symptoms in diabetic patients, it can also lead to the development of peripheral polyneuropathy due to reduced nutrient absorption (See Nutritional Peripheral Neuropathy). Anecdotally, many of these patients exhibit abnormal central and peripheral nerve function, with neuropathic and nociplastic pain being common. Neurologic complications are primarily attributed to nutritional deficiencies, with the B vitamins being most commonly implicated in neuropathy - B1 (thiamine), B2 (riboflavin), B6 (pyridoxine), B9 (folate), and B12 (cobalamin). 
It is crucial for patients undergoing bariatric surgery to have careful nutritional follow-up and routine monitoring of micronutrients to prevent or mitigate these complications. Neurological complications can occur even decades after surgery due to malabsorption. It must be remembered that bariatric surgery involves giving one disease (malabsorption) to treat another (obesity), and there is a trade off that is made.
==Pathophysiology of Neurological Disease==
=== Nutritional State Pre- and Postoperatively ===
Preoperatively: Preoperatively, it is important to note the irony that obesity is often associated with malnutrition. This is particularly true for the morbidly obese. Preoperative studies show that most patients have at least one micronutrient deficiency. The most common preoperative deficiencies identified are Vitamin D, folate, iron, calcium and B12.
Postoperatively: Overall rates of micronutrient deficiencies will depend on many factors, including the type of supplements recommended, patient compliance, and level of postoperative nutritional input. 
A multicenter cross-sectional study in Norway examined micronutrient levels in 490 patients an average of 12 years post–Roux-en-Y gastric bypass (RYGB). Despite high rates of self-reported adherence to recommended vitamin/mineral supplementation (including B12, calcium/vitamin D, and a general multivitamin), clinically significant deficiencies of several B vitamins were still identified. Notably, vitamin B12 was suboptimal in 16% of patients—even though 95% reported adherence to supplementation—and deficiencies of vitamin B1 (thiamine), B2 (riboflavin), and B6 (pyridoxine) were also found. In those non-adherent to supplementation, there were lower levels of folate, B2, B6, B12, and vitamin D.
In a small study of 32 patients in Kuwait of sleeve gastrectomy patients - 16 with neuropathy and 16 without neuropathy - All were provided with supplementation and were followed to 18 months. They found an association with lower levels of B1, B2, and copper. They also found toxic levels of B6, presumably due to the supplements containing too much B6. B12 levels were normal. The authors note that gastric sleeve and bypass patients have different mechanisms for neuropathy.
===Mechanisms===
There are three potential mechanisms for neurologic complications following bariatric surgery.
#Vitamin and mineral deficiencies. This is the most common and most important group and can be due to malabsorption and/or prolonged vomiting. Probably the main cause for the sensory polyneuropathies.
#Mechanical compression and entrapment neuropathies. This might be due to changes in body composition such as loss of protective subcutaneous tissue or due to physical injury from surgery e.g. from retractors.
#There may be an inflammatory mechanism in some cases in combination with nutritional deficiencies.
Specific reasons for micronutrient deficiencies include prolonged vomiting, loss of absorptive surface of the gut, altered diet (food restrictions and new intolerances), bacterial overgrowth, loss of gastric acid (important in the absorption of certain micronutrients), and loss of intrinsic factor (for B12), and duodenojejunal malabsorption (the duodenum is the primary area for absorption of calcium, iron, and B1).
==Prevalence of Peripheral Neuropathy and Risk Factors ==
A study by Thaisetthawatkul et al. found that 16% of patients developed peripheral neuropathy (PN) after bariatric surgery, compared to 3% after cholecystectomy. This study showed that it is bariatric surgery itself not abdominal surgery in general that is causative. The study did not look at prevalence of specific vitamin and mineral deficiencies as it appears from the study description their patients did not undergo comprehensive nutrient testing.
In the same study risk factors for developing neuropathy post-bariatric surgery included the rate and absolute amount of weight loss, prolonged gastrointestinal symptoms, not attending a nutritional clinic, reduced serum albumin and transferrin levels, and postoperative surgical complications requiring hospitalization.
==Clinical Features of Neurological Complications==
===Peripheral neuropathy===
There are three main clinical patterns of peripheral neuropathy.
Sensory predominant polyneuropathies: This is the primary peripheral neuropathy group that is related to nutritional deficiencies. There are two sub-types - large fibre and small fibre neuropathies
These patients often have neuropathic pain but may also complain of weakness. Common examination features are loss of pinprick sensation, vibratory, temperature sensation, and hyperalgesia. Occasionally there is distal weakness 
In the Thaisetthawatkul et al study, sural nerve biopsies showed axonaldegeneration with inflammatory infiltrates. Electrophysiology showed large fibre peripheral neuropathy in 70%, with the remainder having small fibre neuropathy.
Mononeuropathies: This group is mostly carpal tunnel syndrome, but also foot drop, ulnar neuropathy at the elbow, radial mononeuropathy, and meralgia paraesthetica.
Radiculoplexus neuropathies: This is the rarest peripheral neuropathy type and includes lumbosacral and cervical radiculoplexopathies. 
===Other neurological complications===
The following rarer neurological complications can also occur
*Wernicke's encephalopathy (B1) - ophthalmoplegia or nstagmus, ataxia, altered consciousness, hypothermia, vestibular dysfunction, ocular abnormalities, urinary incontinence
*Korsakoff syndrome (B1) - anterograde and retrograde amnesia and confabulations. Can be associated with peripheral neuropathy (dry beriberi)
*Optic neuropathies - central scotoma, night blindness
*Myelopathies
*Restless leg syndrome (B9)
*Myopathies
*Vagal nerve injury
*Subacute combined degeneration (B12)
===Presentation of Different Deficiencies===
Sequelae of B1 deficiency may present very early because liver storage is only 18 days. While B12 deficiency complications may not present for many years.
Summary of important deficiencies and their clinical presentations (Modified from Landais - added B2 and B3). See Nutritional Peripheral Neuropathies for a more comprehensive table.
Vitamin/nutrient	Neurological complications
Vitamin A 	Night blindness, optic neuropathy
Vitamin B1 	Wernicke’s encephalopathy, Korsakoff’s syndrome, acute polyradiculoneuropathy, neuropathy (dry beriberi), optic neuropathy
Vitamin B2 	Peripheral neuropathy, sore throat, mucous membrane oedema, cheilitis, stomatitis, and glossitis
Vitamin B3 	Dermatitis, diarrhoea, dementia, cheilitis, stomatitis, glossitis
Vitamin B6 	Peripheral neuropathy, optic neuropathy, myelopathy
Vitamin B9 	Peripheral neuropathy, optic neuropathy, restless leg syndrome, (affective disorders?)
Vitamin B12 	Myelopathy, peripheral neuropathy, optic neuropathy, (dementia and mental disorders?)
Vitamin D 	Myopathy
Vitamin E 	Myelopathy, peripheral neuropathy
Copper 	Myelopathy, peripheral neuropathy, optic neuropathy, myopathy
Global protein 	Myopathy
==Pain and Psychiatric Disease Post-Surgery==
An RCT by Tan et al in New Zealand randomised patients to sleeve gastrectomy vs gastric bypass, with 52 in each group. There were dramatic changes in medication use in both groups. 
* Diabetes and CVD: There was a large reduction in diabetes and cardiovascular medication prescribing, although there was a higher requirement for diabetes medication in the sleeve gastrectomy group compared to bypass.
*PPIs: There was a long-term trend towards increased PPI prescribing in both groups by 81%.
*Psychiatric: patients took 133% more psychiatric medications over the five years.
* Pain: It trended upwards from 3 years post-operatively, reaching a 50% increase over baseline after 5 years.
*Overall polypharmacy: The total number of medications reduced significantly initially, but by 5 years it was only 10% below baseline in both groups.
Other studies have found an increase in opioid prescribing after bariatric surgery, with particular risk for those using opioids pre-operatively. In a study study of 11,719 patients, regular opioid prescribing continued by one year, with 20% having some use, and only 3% having no use. A longer term study of 2258 patients found a lower rate of continued use at one year of 53%, but with steadily increasing prevalence such that by year 7, opioid use had increased to level 20% above baseline. Authors have theorised that obese individuals have greater pain sensitivity that persists post surgery.
The findings of increased prescribing of psychiatric drugs in the Tan et al study is corroborated by a large cohort study of 24,766 bariatric surgery patients by Morgan et al in Australia. They reported an increase in various negative psychiatric outcomes including increased psychiatric illness presentation (2.3 incidence rate ratio IRR), increased ED attendance (3.0), increased psychiatric hospitalisation (3.0), and increased self-harm (4.7). 25 out of the 261 post-operative deaths were due to suicide. 
It is not entirely clear why psychiatric outcomes tend to be worse after bariatric surgery. Some potential hypothetical mechanisms: "addiction transfer" whereby patients lose the coping mechanism of food, altered brain-gut axis neurotransmitter balance, micronutrient deficiencies for CNS and PNS health, and mismatch of expectations and reality. Regardless, having bariatric surgery does not equal automatic resolution of pain and psychiatric issues. Bariatric surgery is a powerful tool but doesn't address deeply rooted biopsychosocial factors underlying chronic pain and mental health challenges.
==Laboratory Studies==
NZ guidelines state that all bariatric surgery patients should have the following annual blood tests: FBC, Electrolytes, Creatinine, Ferritin, Vitamin B12 + folate, LFTs, 25(OH) vitamin D, Calcium, Parathryoid hormone (PTH), Zinc, Copper, lipids if history of dyslipidaemia If the patient is at higher risk for malabsorption such as a Roux-en-Y bypass, then they should also have Vitamin A and Vitamin E tests. Generally these are done post op, at 3 months, 6 months, 9 months, 12 months and then annually if stable.
The guidelines do not state what to test for if the patient develops peripheral neuropathy. Importantly in this clinical context, the list misses B1, B2, B3, and B6 which have all been implicated in peripheral neuropathy post bariatric surgery. B1, B2, and B3 should be measured looking for deficiency, and B6 measured looking particularly for toxicity as well as deficiency (both can occur and both states can cause neuropathy).
There are many pitfalls in the testing of the B vitamins, please see Nutritional Peripheral Neuropathies. An underlying deficiency is not always found in postbariatric surgery neuropathy patients. 
==Prevention==
All bariatric patients should be on regular supplements and annual laboratory monitoring for life. 
There is a worrying low rate of adherence, for example with one study showing only 37% taking multivitamins at 4 years post-operatively, and another study showing compliance of only 53% at 5 years. Patients should be educated that their risk of nutritional deficiencies does not go away over time. Even with sleeve gastrectomy in compliant patients, about about half will have at least some micronutrient deficiency.
The funded Mvite tablet does not contain the right concentration of vitamins and minerals for bariatric patients. They need to buy appropriate supplements out of pocket. See resources below for appropriate supplements in NZ.
==Prognosis and Treatment ==
If identified and appropriately treated, the prognosis is favourable for peripheral neuropathy. A cohort study of 47 patients with neuropathy post bariatric surgery by Punchai reported resolution of symptoms with appropriate treatment in 40 patients (85%). Four patients had Wenicke encephalopathy which was not reversible, leaving only 3 peripheral neuropathy patients with non reversible symptoms. The most common deficiencies identified in order of prevalence was B1 (30), B6 (12) and B12 (12) equal, and B2 was the rarest with only 1 out of 47 patients.
For patients with persistent chronic pain post-bariatric surgery without evidence of peripheral neuropathy, the prognosis is probably poor, although the long term studies did not assess outcomes by subgroup. The clinician should be aware of the very high rates of psychological distress in bariatric surgery patients and many of these patients probably should be referred to tertiary level MDT.
==Resources==
==See Also==
Obesity and Chronic Pain
==References==
Category:Miscellaneous