Case study

A 35-year-old lady was referred by surgeons for a gastroenterology-nutrition opinion. At 18 years old, while living in social care, she had received a diagnosis of irritable bowel syndrome that had settled after self-management. In her mid-20s she had a miscarriage and developed recurrent severe abdominal pains. She attended gynaecology and was told she had “blocked tubes”, leading to a total abdominal hysterectomy and bilateral salpingo-oophrectomy. Abdominal pains had worsened post-operatively and she had undergone recurrent laparoscopic adhesiolysis. She was given increasing doses of opioids, including a fentanyl patch and lozenges for breakthrough pain. She suffered with severe constipation and bloating and eating worsened the pains. A gastrostomy feeding tube was put in, but because of the pain she was intolerant of even a small volume by drip feeding. She and the surgeons decided to request parenteral nutrition. Her body mass index was above the normal range and no clinically assisted nutrition or hydration was indicated. Cross-sectional imaging and barium follow through showed no adhesional obstruction or structural pathology. Light finger-tip brush strokes over the area of maximum pain elicited patient-reported severe pain and nausea.

 

Introduction

Centrally mediated abdominal pain syndrome (CAPS) and narcotic bowel syndrome (NBS) are now recognised as being related to each other, but are distinct from more common disorders, such as irritable bowel syndrome (IBS) [1]. These disorders have estimated prevalence of 0.5–2.0% that peaks in the mid-30–40s, and they are more common in women than in men.

Both conditions are thought to arise from abnormal processing of pain signals within the central nervous system and, therefore, are centrally mediated. They share some clinical features of neuropathic pain, including a combination of constant and spontaneous pain, allodynia (non-painful stimuli perceived as painful) and hyperalgesia (painful stimuli perceived as being more painful) [2,3].

Opioid-induced hyperalgesia is a counterintuitive concept whereby opioids alter pain-processing neurobiology in sensitised nerves via multiple molecular mechanisms. Pain, therefore, is enhanced. Carefully withdrawing the opioids can result in an overall reduction of the pain levels [4].

 

Centrally mediated abdominal pain and the Narcotic Bowel syndrome

The hallmark of centrally mediated abdominal pain (after exclusion of organic causes) is the  constant or nearly constant nature, which distinguishes it from the episodic pain that is restricted to gastrointestinal physiological events in other functional gut disorders. Centrally mediated pain might also worsen with gastrointestinal physiological events and gastrointestinal function might be impaired, but the pain is nevertheless continuously present at other times. These characteristics are the main clues to diagnosis [5].

A clear trigger for pain onset might occasionally be identified but generally is not. The patient might have a history of concomitant chronic painful conditions, such as fibromyalgia, or other medically unexplained disorders. Patients are frequently psychosocially distressed with poor quality of life and levels of functioning. Physicians should assess maladaptive patient attitudes, beliefs, emotions, behaviours and family and workplace factors, as these could increase the risk of progression to long-term disability [6]. Opioid dose, frequency and route of administration should be detailed, together with a review of dose escalation, chaotic use and emergency department attendance for opioid injections. Narcotic bowel syndrome is characterised by a vicious cycle of escalating doses of opioids in tandem with escalating pain levels.

Examination for erythema ab igne due to hot water bottle use, and the presence of surgical scars and their proximity to the sites of maximum pain should be determined. Carnett’s sign, which is characterised by highly focal pain on palpation alongside the rectus sheath that is worsened with head or leg raising, is a sign of anterior cutaneous nerve entrapment syndrome. This condition may respond to steroid and local anaesthetic injections and should be excluded as part of the examination. A neuropathic or centrally sensitised component is suggested by cutaneous allodynia caused by light brush strokes of the skin and other abdominal skin sensory changes, such as dysaesthesia (tingling or numbness) [2,3].

Iatrogenesis due to continued futile investigations should be avoided, but an initial set of investigations should be considered to rule out organic causes for the pain. Tests might include blood tests, stool samples and/or cross-sectional imaging. Furthermore, unnecessary surgery [3] or escalating levels of clinically assisted nutrition and hydration in the absence of intestinal failure should be avoided.

Adhesions are not considered to be a cause of chronic continuous pain per se. Unless acute obstruction threatens bowel viability, adhesiolysis should be avoided as it is associated with worsening pain and morbidity [1,3].

 

Management

Management of CAPS and NBS should follow the 4 Rs: recognition, relationship, replacement and reduction.

Recognition

A positive and clear diagnosis, including insight into the “wiring” of the central nervous pain system and the counterproductive effects of opioids, helps patient engagement and avoidance of harm. Public Health England provides a helpful resource for patients and professionals [7].

 

Relationship

There is no substitute for time and empathy. The optimum relationship for the patient is with a multidisciplinary team, including pain physicians, clinical psychologists and physical therapists in addition to the gastroenterologist. A holistic and rehabilitative pain management programme should aim to improve function in the face of ongoing pain symptoms and to minimise disability [6].

 

Replacement

Pharmacotherapy might be of limited efficacy, but gut–brain neuromodulators can be used to replace opioids. These include tricyclic antidepressants, gabapentin, pregabalin and duloxetine [3, 8]. Evidence from a large cohort of patients with chronic continuous pain suggests that duloxetine is the most efficacious gut–brain neuromodulator [3]. Additionally, evidence suggests that linaclotide, which is used to treat constipation, has a neuromodulatory effect in chronic continuous abdominal pain and analgesic effects in irritable bowel syndrome [3]. Data from animal models suggest that these effects arise via neuroenteric mechanisms [3].  Peripheral mu-opioid-receptor antagonists, such as naloxegol, can be considered to help opioid-induced dysmotility.

 

Reduction

The opioid regimen should be rationalised and stabilised to a non-escalating dose and longer-acting formulations and a non-injected route of administration should be used. Individualised agreed pathways to avoid injectable opioids and dose escalations can be drawn up in conjunction with the emergency department and the patient’s GP as needed, leading to the patient being directed back to the chronic pain team as an outpatient. Despite improved pain symptoms initially, rapid inpatient opioid detoxification is unfortunately associated with very high relapse rates [4]. The optimum approach to avoid recidivism during and after reduction requires patient engagement is multidisciplinary team support and slow controlled reduction of opioid dose over time to avoid withdrawal side-effects.

 

Conclusions

Outcomes for patients with centrally mediated abdominal pain can be optimised by carefully eliciting the positive clinical features to provide a clear diagnosis; avoiding iatrogenic harms from opioids and unnecessary surgery and by the appropriate use of gut-brain neuromodulators within a chronic pain multi-disciplinary pain management setting.

Dr Peter Paine,  Department of Gastroenterology, Salford Royal Foundation Trust,  Eccles


Learning points 

  • Continuous or nearly continuous chronic abdominal pain is likely to be centrally mediated
  • Opioids and surgery should be avoided for this condition, as they will almost certainly worsen outcomes
  • Optimum management includes gut–brain neuromodulators and a holistic approach by a multidisciplinary team