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Tackling the agonising pain of trigeminal neuralgia

By Dermot - 24th Oct 2016

<p class=”p1″><span class=”s1″>Ima</span>gine feeling excruciating pain when the wind blows against your skin, you brush your teeth or comb your hair? That is the reality of life for the 1,000 or so Irish people with TN, a condition that was the subject of a pain symposium for patients and medical professionals at TCD earlier this month. 

<p class=”p3″>The symposium began with a personal account of TN by Ms Carol Murray, research assistant at the TCD Institute for Neuroscience, one of the main organisers of the symposium. 

<p class=”p3″>Ms Murray said that TN was “the worst pain known to science” and was also known as “suicide pain”. The goal of the evening, she said, was to bridge communications between doctors, nurses, paramedics, patients, and others and to highlight research and knowledge of TN treatments that are available in Ireland. 

<p class=”p3″><span class=”s1″>The average age of onset of TN, said Ms Murray, is 40 years, but she started to experience symptoms at the age of 14 when she got severe headaches, which did not respond to paracetamol, and she was taken into the emergency department (ED) in Galway. The first night in hospital was terrifying she said, with constant pain, vomiting, and belching. </span>

<p class=”p3″><span class=”s1″>It took time to diagnose her condition, Ms Murray said, and before that she underwent numerous tests and scans. The pain eventually left, but it was back, worse then ever, 24 hours later when she felt like someone was stabbing her face with a knife dipped in hot coals. She had an MRI in Cork and was diagnosed with TN. </span>

<p class=”p3″>Ms Murray said she was prescribed with 24 different tablets and had three pain-killing injections per day at one stage and she began to try and accept that she could not do certain things without experiencing pain. The pain eventually left and she returned to school, now in remission, but feeling drained. That was 2001. 

<p class=”p3″>The pain returned in 2005, and 2009 and she started to successfully use sodium valproate, which worked well for pain but made her feel tired. Ms Murray says that she now takes this drug if she has an attack, which she has intermittently, but if it does not work and the chest pain worsens she goes to the ED. 

<p class=”p3″>Ms Murray is now doing a PhD in neuroscience. One of the questions that she has always asked, she said, was why was her body attacking itself? What was causing this pain? One of the things that helped her cope, she said, was the knowledge that she gained from studying the nervous system.

<p class=”p3″>Ms Murray was keen to highlight that doctors and other medical professionals need to believe people when they report pain. She said that while she had great doctors, she remembered some that were “less pleasant” including one that asked her: “I had migraine at your age because I was being bullied in school – are you being bullied in school?” Doctors should realise that a person with such pain is terrified and vulnerable and that they should try and talk to them at eye level to reassure them they are listening, she stated.

<h3 class=”p4″><strong>Communication is key </strong></h3> <p class=”p3″>Prof Paul Durham, Director of Cell Biology and the Centre for Biomedical and Life Sciences at Missouri State University, US, was the symposium’s keynote speaker. He believes that disrupting the communication between glial cells that surround neurons and the neurons themselves can help to address TN. 

<p class=”p3″>Prof Durham met Ms Murray at a scientific meeting in 2014 and after spending 40 minutes talking to her about his research, she invited him to speak at TCD. 

<p class=”p3″>The pain associated with TN, explained Prof Durham, is generated when the trigeminal nerve is stimulated or sensitised. There are three branches of that nerve and there are comorbidities with other types of pain such as migraine and tooth pain he said. The glial cells surrounding the neurons, which convey pain control the excited state of the neuron, so controlling glial cells should control pain, he said. 

<p class=”p3″>“When you have TN attacks, you can’t brush hair, or touch your face, this is sensitisation and we are trying to remove this, so people can carry on with their lives,” said Prof Durham. Researchers want to determine how the TN system is organised at the cellular level, he commented, and how the pain nerve cells can be quietened. 

<p class=”p3″>When doctors cannot identify what is causing TN pain, Prof Durham suggested it might be because the glial cells are not functioning properly. When glial cells and neurons ‘talk’ it can lead to pain he said. The usual situation with sharp pain such as tooth pain is that the glial cells and the neurons talk, but then they stop and the pain stops. In chronic TN pain the talking continues and so does the pain. 

<p class=”p3″>Chronic pain moves from the periphery into the spinal cord, and brain and becomes a brain problem more than anything, said Prof Durham. “We need to lower the activation threshold to all these various stimuli. When there is sensitivity in the peripheral and central nerves, you are in a hyper excitable state,” he said. 

<p class=”p3″><span class=”s1″>Calcitonin gene-related peptide (CGRP) has been found to reduce this kind of nervous excitability, reported Prof Durham. When CGRP is elevated, the person is going to feel more pain, he said, so controlling CGRP must be a focus of TN pain relief. </span>

<p class=”p3″>There are medications available for TN, but less than 30 per cent of them are effective, said Prof Durham. There are some new treatments coming online, but these have not been designed to treat TN, but other conditions like epilepsy, so they may not be ideal treatments. The goal must be to develop new drugs that break the glial-neuronal communications, which is driving the pathology, Prof Durham maintained. 

<p class=”p3″>There is also evidence that medical cannabis and grape seed extract can help relieve TN pain and new evidence is emerging all the time, he noted. 

<h3 class=”p4″><strong>No magic cure, but treatments can help </strong></h3> <p class=”p3″>Dr Josh Keaveny, Consultant Pain Management Specialist, Beaumont Hospital, Dublin, acknowledged that TN is a devastating condition that destroys people’s lives, but said that there are treatments available that work and even better ones coming in the future. 

<p class=”p3″>Dr Keaveny said that the painting <em>The Scream</em> by Edvard Munch depicts the true agony of TN and it is thought that it was drawn by Munch in 1893 after he saw someone screaming in pain in a park. 

<p class=”p3″><span class=”s1″>TN is not a common condition, he said, but it does affect about two people in every 1,000. The pain cannot be measured, but it must be acknowledged and medicine today does that, although it might not have been done so much in the past, he said. The Medical Council now recognises pain as a medical subspecialty, noted Dr Keaveny, and it was among the first in Europe to do so. </span>

<p class=”p3″>He explained that pure TN is accompanied by pain, which strikes like bolts of lightening and then disappears. The symptoms range from burning pain, to darting or shooting pain, with pain-free intervals. It is crucial to get the right diagnosis for pain conditions, which may present in a similar fashion to TN, as the wrong diagnosis can lead to treatments that do more harm than good, he said. 

<p class=”p3″>Trigeminal neuropathy, for example, is different to TN, noted Dr Keaveny. It usually occurs in younger people, there is burning pain and more constant pain. The average age of onset of TN in contrast is 57 years. 

<p class=”p3″>A significant medical issue with TN is sleep disturbance and Dr Keaveny recommended that patients take something to allow them sleep, because if they do not sleep, they do not get better. He said there are a range of treatments, such as anticonvulsant medications, phenol injections, surgical procedures that kill the nerve, such as radio frequency ablation and neuromodulation methods, which alter the way a nerve works by applying low or high frequency stimulations. There are also wireless solutions on the way, which represent the future, said Dr Keaveny. 

<h3 class=”p4″><span class=”s1″><strong>Natural pain suppression </strong></span></h3> <p class=”p3″>A greater scientific understanding of how the body naturally suppresses pain in highly stressful situations could provide new insights to help treat TN, Prof David Finn, Professor of Pharmacology and Therapeutics and co-founder of the Pain Research Centre, NUI Galway, told the symposium. 

<p class=”p3″><span class=”s1″>Prof Finn said that he was interested in asking the question, ‘What is pain?’ And exploring how the body suppresses pain, via what is called endogenous analgesia. </span>

<p class=”p3″>The measurement of pain in an objective way is becoming possible, he said, as MRI scans can now show increases in certain brain regions in response to pain, so there is a signature of pain in the brain. 

<p class=”p3″>He said that a greater understanding too of people that are born without the ability to feel pain, through congenital insensitivity to pain, could also lead to insights that result in new, better treatments for TN. These people often die as teenagers or in their early 20s from the accumulation of injuries, he said. 

<p class=”p3″><span class=”s1″>About one-in-five people suffer from chronic pain in Ireland, reported Prof Finn, which is defined as pain persisting for three to six months or longer. The cost to Ireland of such pain in terms of lost work days is over €5 billion per annum. </span>

<p class=”p3″>When pain is persistent it leads to release of pro-inflammatory molecules, he explained. These pro-inflammatory molecules set up a peripheral or central sensitisation and maintain it and there is enhanced pain transmission to the brain as a result. There is a shutting down of inhibitory pathways, which reduce or dampen down pain in such a situation and there are no longer ‘brakes on pain’. 

<p class=”p3″>One answer is analgesics, like aspirin and ibuprofen, which inhibit prostaglandin and make it less likely that the pain neurons will be activated. Opioids are also commonly used for chronic pain, he said, while anticonvulsants also dampen down communication in the pain pathway, while blocking neurotransmitters in the spinal cord. 

<p class=”p3″>Prof Finn said his research group at NUIG is interested in the body’s natural cannabinoids, which suppress pain. He said that one goal would be to produce a drug that will boost the body’s production of endogenous endocannabinoids. 

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