Is this scenario familiar? You are in pain, so you go to your GP and he or she gives you a prescription for painkillers. They help but a few weeks later the pain feels worse again, so you go back and get a stronger dose. A while later, the pain is bad again…a year or two down the line, and you are on a lot of different painkilling medications and still in pain – in fact the pain is worse than ever and it seems that your condition is deteriorating. That may indeed be the case in some instances, but ironically, in others, the increased pain may actually be CAUSED by your painkilling medicine.
Opiate (derived from opium poppies) or opioid (synthetic opiates) painkillers include codeine, co-codamol, morphine, dihydrocodeine, tramadol and fentanyl, and they are really effective for no more than a month or two; after that you develop a tolerance to them and to achieve the same effect, the dose has to be increased. And then increased again… Sufferers understandably believe they need stronger painkillers in ever stronger doses because they are getting worse.
Taking opiate painkillers actually increases your sensitivity to pain and decreases your natural ability to tolerate pain. The body stops producing endorphins (the body’s natural painkillers) because it is receiving opiates instead. The brain increases the number of receptors for the drug, and the nerve cells in the brain cease to function normally. According to Roger Knaggs, associate professor of pharmacy at Nottingham University and a council member of the British Pain Society, opioids ‘up-regulate’ the body’s pain system so our natural painkilling chemicals, such as endorphins, become less sensitive and effective. He says “Patients affected by opioids in this way will often complain that the nature of their pain has changed or it has spread to other areas, but, in fact, this could be caused by their drugs”.
Separate from their pain-blocking interaction with receptors in the brain, opioids seem to reshape the nervous system to amplify pain signals, even after the original illness or injury subsides. A new study in rats demonstrated that an opioid sets off a chain of immune signals in the spinal cord that amplifies pain rather than dulling it, even after the drug leaves the body. The experiment induced neuropathic pain (the kind that might be experienced from traumatic nerve injury, stroke or nerve damage caused by diabetes) by loosely constricting the sciatic nerve in the thighs of rats. The rats received morphine or a saline control for five days via injections under the skin. As expected, the neuropathic pain due to sciatic nerve constriction continued for another four weeks in the rats that had received the saline, but for the rats that had received morphine, the neuropathic pain continued for 10 weeks – the five-day morphine treatment more than doubled the duration of neuropathic pain. A separate experiment in the same study showed that morphine also worsened neuropathic pain, an effect that lasted for more than a month after morphine treatment had ended.
It used to be thought that pain signalling was a dialogue between nerves, but it has now been shown that it involves glial cells, which provide nutritional support for nerves and clear away metabolic waste. Glia recognize chemical signals from nerves and respond by releasing chemical immune signals that influence communication between nerves. With abnormal pain signalling from nerves, glia respond by turning up the volume in spinal cord pain pathways. This results in the adaptations of painful sensations being exaggerated. Opioids are also a chemical signal for glia. In the study, when morphine was administered in the presence of neuropathic pain, the glial cells went into overdrive. The glia released more immune signals, keeping the ‘pain volume’ turned up higher and for longer. After morphine, the researchers found, those pain-activated glial cells became more sensitive to the next pain stimuli. As the researchers put it, “Opioids exaggerate pain.”
Sometimes people are surprised to discover that when they stop taking opioid medicines, their pain goes away or at least is substantially reduced. Many GPs and therapists have encountered the sheer panic, distress and numerous justifications for continuance from patients when it is suggested that their pain medication is not helping and should be stopped or reduced. This is partly because the patient naturally fears the pain will get worse, but mostly because they are now physically and emotionally addicted to the painkiller. Even the lower dose 8mg codeine or 8/500 co-codamol available to buy from pharmacies can become addictive after just three days of use.
No one should just stop taking opioid painkillers but must work out a scheduled withdrawal programme under the supervision of their GP. The degeneration of the nerve cells in the brain causes a physical dependency on an external supply of opiates, so reducing or stopping intake of the drug causes a painful series of physical changes called the withdrawal syndrome. ‘Going cold turkey’ is associated with intense withdrawal symptoms which can be prolonged, characterized by severe discomfort, including diarrhoea, abdominal pain and cramping, vomiting, runny nose, eye tearing, yawning, sweating, agitation, restlessness, twitching and tremors, back and bone pain, and intense craving for the drug. The patient takes the pills and feels better, so assumes that the medication is working, when it is only staving off withdrawal.
The use of opioids has serious side effects. Opioids affect the area of the brain responsible for respiration and some can depress the rate of breathing, occasionally leading to accidental death. Other side-effects include constipation and drowsiness, impairment of the immune system making people more prone to infections and an increased risk of heart disease. They also reduce levels of oestrogen and testosterone.
Opiate/opioid painkillers have an important place in medicine, but where they were once only prescribed short term after trauma injury or as palliative care for people dying of cancer, in recent years they have been increasingly prescribed for long term conditions such as back pain, arthritis, fibromyalgia and endometriosis. So why are GPs writing out more opioid prescriptions than ever? The trouble is that when a patient presents with pain, the hard pressed GP has few options. There is no time in a 10 minute consultation to talk to patients about lifestyle choices such as exercise, diet, physical therapies, giving up smoking or losing weight, which can all affect pain, and little option in today’s cash-strapped NHS to send people to physiotherapists or pain clinics, so the GP has to reach for the prescription pad. Now they have been advised not to prescribe non-steroidal anti-inflammatory drugs or NSAIDs to some patients because of concerns about a higher risk of gastric bleeding and heart attacks, or paracetamol, which is associated with an increased risk of gastric bleeding, cardiovascular disease and impaired kidney function, they are left wondering what they can do for patients for long-term pain.
In the USA, the latest CDC guidelines state that opioids should be avoided if possible, with the exception of cancer pain and end-of-life palliative care.
Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation http://www.pnas.org/content/113/24/E3441