MCAS: Pain

Pain is an unfortunate fact of life with MCAS. Muscle fatigue and weakness are common complaints, but myositis and rhabdomyolysis are rare. Some patients have elevated creatine kinase and/or aldolase, but have no related symptoms.

Bone pain is frequently reported with MCAS. Osteopenia and osteoporosis are common findings. Focal osteosclerosis is also sometimes found, but less frequently. Joints are often painful, which can lead to diagnoses of osteoarthritis, seronegative rheumatoid arthritis, fibromyalgia and polymyalgia rheumatica. Pain can migrate and is often poorly localized. Patients often feel pain in joints, bones and soft tissues, sometimes inconsistently.

Mast cells have been implicated in several pain disorders. Chronic lower back pain has been hypothesized to be related to mast cell activation for over a decade. Complex regional pain syndrome Type I, formerly known as reflex sympathetic dystrophy (RSD) and reflex neurovascular dystrophy (RND), is the most painful long term condition described. It is marked by neurogenic inflammation (nervous system swelling), sensitization of pain receptors and circulatory problems that cause swelling and color changes. It can affect any part of the body. Mast cells have been linked to the inflammatory response seen in CRPS patients.

Neurons with noradrenaline, serotonin and opioidergic receptors inhibit transmission of pain signals. (This is why taking opiates works for pain – it binds to these opioidergic receptors and suppresses the pain signals.) In the spinal cord, pain signals from the peripheral pathways meet up with the spinal pain signals to send to the brain. Here is where molecules like GABA, opioids made in the body and serotonin control pain transmission.

In chronic pain, serotonin acts to amplify the peripheral pain signals instead of suppress them. Increased serotonin levels and mast cell counts are found in many patients with chronic abdominal pain. About 95% of serotonin in the body is found in the peritoneal cavity, which explains the chronic pain many people feel in this region. Mediators released from colon biopsies in IBS patients were proven to excite the local nerves and activate pain receptors. Serotonin is one of these mediators.

Some antidepressants are known to affect serotonin secretion from mast cells. In particular, tricyclic antidepressants inhibit serotonin release in a dose dependent manner at higher concentrations. Clomipramine was seen to be the most effective, with amitriptyline and doxepin inhibiting release of serotonin and histamine at higher doses. All three were found to affect both uptake and reuptake of serotonin by mast cells and therefore lowering the relative concentration of serotonin in the local environment.

MCAS pain is often difficult to treat with typical pain medications. Antihistamines and cromolyn should be used to manage pain where possible. For bone related pain, bisphosphonates are usually effective. There is some data to suggest hydroxyurea can help manage pain in MCAS patients.

 

References:

Xinning Li, MD; Keith Kenter, MD; Ashley Newman, BS; Stephen O’Brien, MD, MBA. Allergy/ Hypersensitivity Reactions as a Predisposing Factor to Complex Regional Pain Syndrome I in Orthopedic Patients. Orthopedics 2014: Volume 37 · Issue 3: e286-e291

Giovanni Barbara, et al. Mast Cell-Dependent Excitation of Visceral-Nociceptive Sensory Neurons in Irritable Bowel Syndrome. Gastroenterology Volume 132, Issue 1, January 2007, Pages 26–37.

Ferjan, F. Erjavec . Changes in histamine and serotonin secretion from rat peritoneal mast cells caused by antidepressants. Inflammation Research 1996, Volume 45, Issue 3, pp 141-144.

Barbara, V. Stanghellini, R. De Giorgio et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology, vol. 126, no. 3, pp. 693–702, 2004.

Barbara, B. Wang, V. Stanghellini et al. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology, vol. 132, no. 1, pp. 26–37, 2007.

Afrin, Lawrence B. Diagnosis, presentation and management of mast cell activation syndrome. 2013. Mast cells.