Pain is essential to our existence. People who lose pain sensation in a limb, because of a nerve injury or a degeneration of their nerves, as can happen in diabetes, can sustain a bad burn or other injury without even realising that anything has happened. Similarly, people can have a completely painless heart attack and be unaware that they have heart disease until their heart finally fails. Pain tells us about injury, and our fear of pain keeps us out of mischief! The paradox of pain is that, at times, it lasts for long after the injury, or occurs without any injury or damage. It then no longer has a useful purpose. Rather than being an important survival mechanism, it becomes a debilitating problem that interferes with our lives.
THE NATURE OF PAIN
I keep hearing the terms ‘acute’ and ‘chronic’ pain. What do these mean?
The terms ‘acute’ and ‘chronic’ refer to timing rather than severity. ‘Acute’ implies that the pain is of rapid onset but not prolonged; ‘chronic’ implies that the pain persists past the usual course of an injury, or recurs every few days weeks or months. The pain of irritable bowel syndrome (IBS) is usually thought of as chronic.
Are there any general differences between acute and chronic pain?
Acute pain is usually caused by some sort of injury such as the trauma of a broken arm, inflammation in an appendix, or the death of a portion of heart muscle, as in a heart attack. Although we expect the severity of the pain to be in proportion to the degree of damage to our body, this isn’t always the case. In acute pain, nerve pathways descending from the brain to the spinal cord help to cut down the passage of pain signals to the brain. This is presumably an evolutionary adaptation to allow us to continue to function in the short term despite our injury. In addition, acute pain is often accompanied by a heightened state of awareness and activity.
By contrast, chronic pain may happen without any apparent injury, or even after something has been removed – for example, the ‘phantom leg’ pain that can occur after amputation. Moreover, it is thought that the descending nerve pathways from the brain no longer help to lessen the pain signal but may instead increase it. Thus, the pain signal that occurs in the spinal cord can be modified so that the nerve cells seem to become hypersensitive. Signals arising from normal function are amplified to the level of pain. In irritable bowel syndrome, this phenomenon has come to be known as ‘visceral hypersensitivity’ (visceral refers to the internal organs, particularly the intestine.
Do acute and chronic pain make us behave and feel differently?
Acute pain usually stimulates people into action. Chronic pain is frequently accompanied by lethargy and depression.
Do these two types of pain respond equally well to painkillers?
Sadly, chronic pain responds relatively poorly to painkillers (analgesics), but it does better with antidepressants. The following table lists the differences between acute and chronic pain.
Usually associated with tissue injury
Usually no tissue injury
Heightened state of arousal and activity
Depression and lethargy
Responds well to analgesics
Responds poorly to analgesics
Antidespressants can be very effective
What are the typical symptoms of irritable bowel syndrome pain?
The symptoms vary widely between people, and even in the same person over time. In order to be able to compare research studies better, conferences of gastroenterologists (doctors specialising in the gut) have been run to agree on diagnostic criteria for irritable bowel syndrome. These conferences were held in Rome, and their deliberations are currently known as the ‘Rome III criteria’. The rationale for these criteria is to relate the symptoms to abnormal bowel function. If there aren’t any ‘alarm symptoms’ or abnormalities on physical examination, the diagnosis is almost certainly irritable bowel syndrome.
THE DIAGNOSTIC CRITERIA FOR IRRITABLE BOWEL SYNDROME (IBS) BASED ON THE ROME III CONFERENCE (2006)
Recurrent abdominal pain or discomfort for at least 3 days per month in the last 3 months associated with two or more of the following features:
1 Improvement with defecation
2 An onset associated with a change in frequency of the stool
3 An onset associated with a change in form (appearance) of the stool
Other symptoms that together support the diagnosis of irritable bowel syndrome include:
• An unusual frequency of the stools (more than three a day, or fewer than three a week)
• An abnormal form of the stools (hard/lumpy or loose/watery)
• Abnormal passage of the stools
• The passage of mucus
• Bloating or a feeling of abdominal distension
My doctor said something about the ‘right iliac fossa’ being a common site for pain in irritable bowel syndrome. What is the right iliac fossa?
The right iliac fossa is in the lower right quadrant of the abdomen. There are various systems for describing the location of pain in the abdomen and most doctors use which ever term seems to describe the pain best. The simplest system involves dividing the abdomen into four quadrants by vertical and horizontal lines through the umbilicus (belly button). A more accurate system divides the abdomen into nine regions by two vertical and horizontal lines. The most commonly used terms include the right and left ‘iliac fossa’, denoting the lowermost parts of the abdomen, and ‘epigastric’ denoting the uppermost central part.
Where do people most commonly get pain caused by irritable bowel syndrome?
The pain is usually in the abdomen, mostly in the lower right corner, which your doctor will call your ‘right iliac fossa’. This is where the caecum – the first part of the large bowel – is found. The small intestine opens into the caecum, and the caecum is frequently distended. This is probably why it is a common Right Left hypochondrial hypochondrial Right Left lumbar lumbar Right Left iliac fossa iliac fossa. The nine regions of the abdomen. site for pain. Almost as frequent is pain in the left lower corner, the left iliac fossa. This area overlies the sigmoid colon, just above the rectum. It is here that you hold your stool prior to defecation. This area often goes into spasm, and often becomes distended as a result of constipation.
Can irritable bowel syndrome cause pain anywhere else?
irritable bowel syndrome pain can occur anywhere between the nipples and the thighs, front or back. It can be of a stabbing nature, very brief and lasting for only a few seconds, or it can be spread over a wider area and be poorly localised, which means you can’t put your finger on the single spot where the pain is coming from.
Is the pain always the same?
No, unlike the pain from diseases with a structural abnormality (cancer, an ulcer, bowel obstruction, etc.), in which the nature, location and character of the pain are always the same, irritable bowel syndrome pain can vary in both location and severity.
What’s actually causing my pain?
Your pain is probably due to strong contractions of your bowel, or your gut may be distended by faeces or gas. But it may also simply reflect your gut’s normal function.
How often do people normally get symptoms from irritable bowel syndrome?
There are no hard-and-fast rules. Symptoms may disappear for weeks or months, and then reappear in clusters with a bad week or two.They are often better during times when you can relax, such as holidays, and worse when things are stressful. In one survey of 59 people with irritable bowel syndrome over a 12-week period, most reported at least one symptom on over 50% of days, with pain or discomfort on 33% of days, bloating on 28% of days, and altered stool form on 25% of days.
Why is it worse when I’m stressed?
More than any other of our senses, pain is integrated with our emotions. Nerve pathways from centres in the brain that deal with emotion can amplify or reduce the pain signals. This occurs within the brain and also in the spinal cord before the pain signal reaches the brain.
What’s the difference between irritable bowel syndrome and functional abdominal pain syndrome?
Functional abdominal pain syndrome (also called chronic idiopathic abdominal pain or chronic functional abdominal pain) is fortunately uncommon. It is a severe pain that occurs daily and disrupts normal daily activities. Unlike the pain of irritable bowel syndrome, it is not related to bowel function. Moreover, it can last into the night and disturb sleep, something that is unusual for irritable bowel syndrome. It is usually associated with psychological problems that are obvious to the doctor but are often minimised or denied by the patient, who is desperate to discover a physical cause for the pain. The cause of this syndrome is unknown.
Do simple painkillers work for irritable bowel syndrome pain?
The simple painkillers (analgesics) that can be purchased at the chemist’s do not work for irritable bowel syndrome pain. If they do work on you, you should question the diagnosis. Codeine-based analgesics (such as codeine phosphate and dihydrocodeine) and paracetamol/codeine combinations (for example, co-codamol, co-dydramol, Kapake, Solpadol and Tylex) are to some extent helpful but usually cause constipation. Codeine-based medicines can be the beginning of a vicious circle, with constipation making the pain worse, so the person takes more tablets, so the constipation gets worse still.
I once had an injection of pethidine and it worked really well for my pain. But my doctor wouldn’t give me any more. Why is that?
Pethidine is a potent opiate analgesic. Doctors are extremely reluctant to use opiates in conditions with chronic pain, fearing that physical dependence and addiction may develop. This may seem a little paternalistic and cruel, but all doctors have seen patients who, after receiving ill-advised treatment with an opiate, find themselves having to contend both with the original illness and a drug addiction.
‘Opiate’ refers to drugs originally produced from the immature seed capsules of the opium poppy plant. Our nervous system produces its own opiate-like chemicals called endorphins. Their principal role is to reduce pain, and many of the cells involved in pain processing have receptors for the endorphin molecules on their surface.These receptors also interact with opiate drugs and have therefore been called ‘opiate receptors’. In the bowel, however, activation of these opiate receptors leads to relaxation of the bowel muscle and a profound slowing in function. This is why opiate-based analgesics (painkillers) such as codeine and morphine can cause severe constipation, and why opiate-based drugs can relieve diarrhoea. Codeine is a weak opiate, but pethidine, morphine and diamorphine are all potent opiates. They are very powerful painkillers.
There are several problems with using opiate drugs, including tolerance, physical dependence and addiction. Tolerance means that the body gets used to the drug, so that an increasing dose is required to produce the same effect over time. This doesn’t matter if the drug is being given for a short period for acute pain, such as after an operation, or if the patient has a terminal condition. However, it becomes a real problem if the opiate is taken for conditions that last a lifetime.
Physical dependence means that if the drug is stopped suddenly after having been taken long term, usually 1 month or longer, withdrawal symptoms can arise. These include severe anxiety, an unstable mood and physical symptoms such as palpitations, sweating and nausea. Addiction is a form of psychological dependence – people find that they cannot manage psychologically without the drug and resort to extreme behaviour to get it and take it. This does not mean that all or even any of these problems will arise in individuals taking opiates for prolonged periods, particularly when they are taken for acute pain. But problems occur often enough for great care to be needed with the use of these drugs.
Smooth muscle relaxants (antispasmodics)
My doctor’s said I ought to try a smooth muscle relaxant. What is this?
Smooth muscle relaxants are medicines that are believed to relax the smooth muscle of the bowel, that is, the muscle in the wall of the bowel. They work either directly on the muscle or by inhibiting the nerves that stimulate the gut muscles (in which case they are known as anticholinergic or antimuscarinic drugs). They are believed to reduce the pain of irritable bowel syndrome by treating and preventing spasm.
Method Of Action
Direct smooth muscle relaxation
Direct smooth muscle relaxation
Direct smooth muscle relaxation
Do these smooth muscle relaxants have any side effects?
They are believed to be safe and mostly free of side effects. Most are available without prescription. Anticholinergic drugs can cause a dry mouth, blurred vision and constipation if they are used in higher doses. Anticholinergic drugs should not be used by people with glaucoma (increased pressure within the eyes), and they can occasionally cause elderly people to become confused. In the doses used for irritable bowel syndrome, however, there are usually no significant side effects. Peppermint oil can sometimes cause heartburn.
But do they work?
Yes, in some people, some of the time and to some extent. There have been many studies of these preparations in people with irritable bowel syndrome. The studies are, however, difficult to interpret because the ‘placebo response rate’ – the number of people who improve while taking the sham drug – in irritable bowel syndrome trials varies from 20% to over 80%. But in most trials, the muscle relaxant was better than the placebo, and so it’s definitely worth trying them as they may help to relieve your symptoms.
When should I take my antispasmodics?
You should take them about 30 minutes before meals as they take that length of time to work. You can take them regularly or intermittently.They combine well with other medications and treatments for irritable bowel syndrome.Try different antispasmodics to find one that works for you. Antidepressants Low-dose tricyclic antidepressants These are possibly the most potent medicines for irritable bowel syndrome pain.
What are tricyclic antidepressants?
These were the first group of antidepressant drugs that really worked and were relatively safe. Amitriptyline was the first of the group and has been in use for over 50 years. Exactly how they work is still unclear, but they seem to increase the levels of the transmitters noradrenaline (norepinephrine) and serotonin within the brain by preventing them being taken up again by cells once they have been secreted. This gives them longer to act.
Are they analgesics?
You would not take tricyclic antidepressants for a twisted ankle, so they are not analgesic in the sense that they reduce acute pain. But they do reduce chronic pain and are extremely useful for this. Early on in the history of these drugs, it was noticed that some people with depression felt less pain soon after starting a tricyclic, long before their depression lifted. There is now compelling evidence that the activity of these medicines against chronic pain is independent of their effect on depression and occurs at much lower doses. Tricyclics take 2–3 weeks or more to lift a depression, but may work for pain almost immediately. Some individuals notice a benefit within a day, although 3–7 days is more common.
I’m not sure what dose of amitriptyline I should be taking. What is meant by a low dose?
The starting dose of amitriptyline for depression is 75 mg (milligrams). This dose can be gradually increased in depression to 200 mg each day. By contrast, the starting dose for pain and irritable bowel syndrome is usually 10 mg a day.This dose is often successful, but if not, it can be increased by 10–25 mg every week. For irritable bowel syndrome, I usually recommend a maximum of 50 mg a day, although it has been used for pain in higher doses.
Is low-dose amitriptyline used to treat any other pains?
It is used for most conditions in which chronic pain is a problem, including rheumatoid arthritis, back pain, sciatica, headaches and cancer-related pain.
Does it have to be taken all the time?
It has to be taken continuously for depression and should not be stopped suddenly. But this is not the case when it is used for pain. It may work better if it is taken continuously, but it can be used intermittently. Many people taking low-dose amitriptyline stop and restart it depending on what sort of a week they are having. If you are taking more than a very low dose, for instance more than 50 mg a day, you would probably be better off tapering the dose down over a week rather than stopping it suddenly. The pain does not rebound (bounce back worse) if it is stopped.
I’m worried that I could get addicted to my tricyclics. Could that happen?
No, they’re not addictive. There are people whose depression rebounds if they stop taking the drug, but otherwise there are usually no withdrawal effects. Most family doctors will have a lot of experience in using these types of medication. You should not hesitate to seek their advice.
What are the side effects?
Side effects are unfortunately common with tricyclic antidepressants. They usually cause drowsiness, a dry mouth, blurred vision, constipation, urinary retention (difficulty passing urine) and sexual dysfunction. The drowsiness may be apparent even with the very low doses used for pain in irritable bowel syndrome. It may be better to take them at night, but you should start the medication at a weekend as the drowsiness can last into the next day. Tricyclics usually help you to sleep, but occasionally they disturb sleep, sometimes causing nightmares. When the tablets are taken continuously, however, the side effects wear off after 2–3 weeks. In the long term, some people complain of weight gain. In larger doses, tricyclics can cause serious side effects with abnormal heart rhythms in people with heart disease or more convulsions in people with epilepsy. They are dangerous in overdose because of their effect on the heart.
I tend to be very susceptible to side effects from drugs -I doubt if I would tolerate amitriptyline.
It’s interesting that some people with irritable bowel syndrome are intolerant of many drugs because of side effects. However, if you have a lot of trouble with irritable bowel syndrome, it’s much better for you to try amitriptyline than avoid it. The smallest size tablet is 10 mg, and you can also get it as a syrup (25 mg in each 5 ml spoonful). Start with 10 mg at night, or less if you can break the tablet. This is a very small dose compared with what is prescribed for depression (75–150 mg a day), and most people will have minimal side effects. If you take it continuously and try to work through any side effects, the side effects will wear off, but your irritable bowel syndrome will continue to improve.
I’m finding it really hard to cope with the drowsiness that my ami triptyline causes. Are the other tricyclic antidepressants any better?
In short, yes. Amitriptyline has been the best studied with respect to pain management, but the other tricyclics probably work just as well. Amoxapine, imipramine, lofepramine and nortriptyline are all less sedative than amitriptyline, which means that they cause less drowsiness. Lofepramine also causes less of a dry mouth. The starting dose of lofepramine for depression is 140 mg, and it is only available as 70 mg tablets or as a syrup containing 70 mg in each 5 ml spoonful, so start with 35 mg a day. Imipramine (similar to desipramine (US)) is dosed in the same levels as amitriptyline and is available in 10 mg tablets.
Would a full dose of a tricyclic antidepressant work better for irritable bowel syndrome than a low dose?
It may be worthwhile slowly increasing the dose to the full antidepressant dose. For instance, the doctor can increase your dose of amitriptyline by 10–25 mg every week or so up to 150 mg a day for a normal adult. The problem is that, at that dose, it will cause constipation. This may be to your advantage if your problem is diarrhoea, but otherwise the tricyclic may make your irritable bowel syndrome worse.
What antidepressant should I use if I’m depressed and constipated?
There’s a class of antidepressants called SSRIs (selective serotonin reuptake inhibitors), which rarely cause constipation and are more likely to cause diarrhoea. Selective serotonin reuptake inhibitors (SSRIs)
What are SSRIs?
Some of the nerve cells in the brain release a transmitter called serotonin (also known as 5-hydroxytryptamine or 5-HT). The SSRIs – citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline – selectively stop this serotonin being taken back up again after it has been secreted from the nerves. They therefore increase the levels of serotonin in the brain, and this is thought to be how they work in depression. They are as effective as the tricyclic drugs for depression but usually have far fewer, if any, side effects.
Do SSRIs have an effect on the gut too?
The enteric nervous system (the nervous system of the gut) uses much more serotonin than the brain so one would expect SSRIS to have a profound effect on the gut. Surprisingly, however, although a few patients have some gastrointestinal side effects such as diarrhoea, nausea and lack of appetite, most people notice little if any change in their gut function.
Could SSRIs help my irritable bowel syndrome?
SRIs are very helpful in people with irritable bowel syndrome who are also depressed, and they are then used continuously in full doses. But for pain they are probably less effective than low-dose tricyclics.
Could I take SSRIs and tricyclics together?
Doctors do occasionally use a full dose of an SSRI for depression together with a low dose of a tricyclic for pain. So you may be given both by your doctor, depending on your circumstances, and this may work well for you.
New Medicines For Irritable Bowel Syndrome
One of the ‘problems‘ in introducing new drugs for irritable bowel syndrome is that no one dies from irritable bowel syndrome! This may seem a preposterous statement to make, but it does mean that new drugs specifically for irritable bowel syndrome have to be virtually 100% safe to be worth taking, and this is probably impossible. New drugs usually act to change the levels of neurotransmitters (transmitters between nerve cells) such as serotonin, which are found throughout the body, being used for different things in different places. So taking a drug that has effects all through the body can cause unexpected consequences.
The problem of introducing new drugs is shown by the case of the drug alosetron. This was withdrawn after a small significant risk of serious, even life-threatening side effects was found, although it was reintroduced after pressure from patient groups and manufacturers. It is not, however, available in the UK.
Alosetron (brand name Lotronex) is a ‘selective serotonin 5-HT3 receptor antagonist’. That means that it blocks the action of serotonin on one of its receptors, called the 5-HT3 receptor. The most important action of 5-HT3receptors is to transmit pain signals from the bowel to the brain by activating sensory nerve cells that are involved in pain sensation in the gut. Serotonin released from other cells in the gut (called enterochromaffin or EC cells) can also stimulate 5-HT3receptors on an important nerve called the vagus nerve. This can then lead to nausea and non-painful gut sensations, such as bloating and fullness.
Blocking the 5-HT3 receptors may therefore reduce the pain, the need to go to the toilet quickly once you feel you need to (called urgency) and other symptoms associated with the hypersensitivity of diarrhoea-predominant irritable bowel syndrome (IBS-D). It can, however, only be used in IBS-D, because it causes constipation.
How effective is alosetron?
There have been a number of clinical trials with alosetron. For example, after 12 weeks of treatment in one of these studies, 76% ofpeople treated with alosetron had a moderate or substantial improvement in their IBS-D symptoms compared with 44% of those treated with a placebo (a sham treatment). This has led some people to claim that alosetron is ‘highly efficacious’ or even a ‘miracle’ treatment. Others, however, point out that the number of people responding to the drug in most studies was only 10–20% more than the number who responded to the placebo.
What side effects does alosetron have?
In studies, some side effects occurred more frequently with alosetron than with the placebo treatment. These included constipation (29% versus 6% with placebo), abdominal discomfort or pain (7% versus 4%) and nausea (6% versus 5%). For most people, the constipation was mild and transient, occurred just once during the first month of treatment, and resolved on its own or with a break in treatment.
However, serious side effects also occurred. These included severe complications of constipation, ischaemic colitis, hospitalisation, surgery and death. Complications of constipation occur when faeces are impacted so hard within the bowel that the wall perforates, leading to potentially fatal infections in the body cavity. Ischaemic colitis is the interruption of blood flow to the bowel and can resolve itself without problems or can lead to death of part of the gut and life-threatening complications.
Serious complications related to constipation (e.g. obstruction, perforation, impaction or death) occurredin approximately 1 out of every 1000 people taking alosetron. In one study, the risk of ischaemic colitis in women taking it was about 3 in every 1000 women over 6 months. As a result, the manufacturer, GlaxoSmith Kline, voluntarily withdrew alosetron from the US market in November 2000.
In November 2002, however, alosetron was reintroduced under a restricted-accessprogramme for women with severe IBS-D lasting 6 months or longer who did not have any anatomical or biochemical abnormalities of their gastrointestinal tract and who had failed to respond to traditional therapy. Severe IBS-D, as defined in the package information for alosetron,refers to diarrhoea with one or more of the following features:frequent and severe abdominal pain or discomfort, frequent urgency of stool and incontinence of stool, and disability or restrictionof daily activities. Alosetron is not available in the UK.
Do you think alosetron should be available in the UK?
Nothing is completely safe, and the risks of new drugs are difficult to quantify. If people with severe IBS-D are willing to take what is likely to be a small risk, I believe that this drug should be available for them to try.
What is tegaserod?
Tegaserod (brand name Zelnorm) is a ‘selective serotonin type 4 (5-HT4) receptor partial agonist’. That’s a bit of a mouthful but just means that it partially mimics the action of serotonin at one of its receptors. This receptor can be found on the muscle cells of the gut and on nerve cells that supply the gut. When it is activated, it stimulates peristalsis (co-ordinated contractions of the muscles of the gut to propel the contents along) and the secretion of water and digestive juices into the gut. It is therefore used for women with irritable bowel syndrome whose primary bowel symptom is constipation (IBS-C). Activation of the 5-HT4receptor may also reverse visceral hypersensitivity and reduce pain. Tegaserod is not yet licensed for treatment in the UK.
How effective is tegaserod?
In clinical trials involving mainly women with IBS-C, up to 50% had either considerable or complete relief of their constipation, and about 40% had relief from pain. Most of the benefit occurred within a few weeks of starting treatment. The placebo effect (the improvement occurring through the use of sham medication) was, however, also high. In three trials including a total of 2470 women, about 14% more women benefited from tegaserod compared with the placebo after 1 month of treatment.
Statistically, these results were highly significant, so it seems likely that tegaserod will be successful in a proportion of people with severe constipation. Those with severe IBS-C who do not respond to current medical treatment are often desperate to find something that will help them put their life back on track, so it’s frustrating that tegaserod is not yet licensed in the UK.
Can men use tegaserod too?
They probably can, but it has been mainly tested on women. It is not yet apparent whether this will have any implications when tegaserod is finally licensed.
What are the side effects of tegaserod?
Mild diarrhoea especially in the first week of treatment was the most frequent adverse event: it affected 9–33% of people who took tegaserod. Other reported adverse events included abdominal pain, nausea and headache. These side effects occurred just as often with tegaserod as with placebo so may reflect the irritable bowel syndrome more than the treatment.
There have been isolated reports of ischaemic colitis in patients taking tegaserod. Ischaemic colitis is a serious inflammation of the wall of the large bowel that occurs when there is not enough blood supply. It is an uncommon condition even in people with a poor circulation, and may possibly occur as a consequence of longstanding severe constipation. It is not yet clear whether the reports of ischaemic colitis in people taking tegaserod are a coincidence and nothing to do with the drug, or whether ischaemic colitis is a real risk with tegaserod. In any case, the risk is likely to be very small.
Do you think tegaserod should be available in the UK?
Nothing is completely safe, and the risks of new drugs are difficult to assess. If people with severe IBS-C are willing to take what is probably a small risk, I believe that this drug should be made available for them to try.
What is melatonin?
Melatonin is closely related to serotonin. It is secreted by the pineal gland in the brain and may have a function in controlling the sleep–wake cycle. Its secretion is enhanced during darkness and suppressed during daylight. Melatonin has been found to have a sleep-promoting effect and is promoted as being helpful for jet lag.
Is melatonin useful for irritable bowel syndrome?
Only one small study from Singapore has tested melatonin on people with irritable bowel syndrome who also had disturbed sleep. A dose of 3 mg of melatonin was used each night for 2 weeks and then compared with a placebo (sham treatment). Interestingly, the melatonin failed to improve sleep. However, there was a significant improvement in abdominal pain and rectal sensitivity. Stool frequency, stool form and bloating were not improved.
Can I get melatonin easily?
Melatonin is not an established treatment for irritable bowel syndrome. I have mentioned it here because melatonin is available in most countries, like the UK, without prescription and is regarded as safe.
Are any other drugs being developed?
There are several drugs in the early stages of development and testing.
Cilansetron is a new ‘selective serotonin 5-HT3 receptor antagonist’, similar to alosetron (see an earlier question), that is currently being developed. Two trials so far have shown it to be beneficial in IBS-D. However, the UK’s Medicines and Healthcare products Regulatory Agency and the US Food and Drug Administration have asked for further trials before they will approve it.
Renazapride is a new drug being developed for all types of irritable bowel syndrome. It has a serotonin 5-HT4 receptor agonist effect similar to that of tegaserod, as well as a 5-HT3receptor antagonist action. It may combine the beneficial actions of both the new drugs discussed above, similar to alosetron. A study involving 1700 women with IBS-C is currently being planned in the USA.
Asimadoline is a drug called a kappa opioid that may help with symptoms of pain. Unlike other opioid drugs such as morphine or codeine, asimadoline only works on one of the three opioid receptors. The kappa receptor only exists outside the brain, and asimadoline does not cross into the brain, so it doesn’t have a sedative effect and shouldn’t be addictive.
Talnetant is called a neurokinin-3 antagonist. It may help with the oversensitivity of the muscles in the colon.
Pain is not always present in irritable bowel syndrome, and in some people it is not a major factor. In others, it can be severe and impossible to ignore. It can also be difficult to accept that severe pain is not a consequence of a serious problem – it’s all to easy to think that the pain of irritable bowel syndrome must be due to a ‘blockage’ or ‘a growth’. It is all the more worrying as simple analgesics (painkillers) fail to work here.
Visceral hypersensitivity, or how the normal function of internal organs can manifest as pain on the causes of irritable bowel syndrome. Pain in irritable bowel syndrome does not represent physical damage. But it is not a purely psychological phenomenon either. It may be thought of as a ‘signalling problem’ between the gut and the brain. As a result, simple analgesics do not work. Smooth muscle relaxant drugs, called antispasmodics, work to some extent by reducing spasm and dampening down strong contractions. Codeine and other opiate-based drugs do reduce the pain but at the cost of reducing the gut’s muscular activity and propulsion. The resulting constipation will cause worsening pain.
The best treatments for irritable bowel syndrome pain modify the signalling pathway between the gut and the brain. Most successful in this respect is treatment with low-dose tricyclic antidepressants. The SSRIs are also worth trying. With our increasing understanding of the signalling pathways, and especially of the role of serotonin, new drugs are becoming available. In the meantime, it is unfortunate but inevitable that people with irritable bowel syndrome may have to put up with a degree of chronic pain.
People with irritable bowel syndrome should overcome their reluctance to try low-dose amitriptyline and other antidepressants. Most doctors know of individuals whose pain improved dramatically with these medications even after nothing else had worked.
How can my doctor be so sure that my pain is ‘nothing to worry about’?
Different diseases present with different symptom patterns. Although there is often an overlap in the symptoms of different illnesses, we can recognise distinct patterns. As the doctor listens to your symptoms, he or she will be looking for distinct patterns that fit particular diseases. There is no mystery to this. Your doctor will also be listening out for symptoms that suggest more serious pathology, so-called ‘alarm symptoms’.
What do doctors mean by ‘alarm symptoms’?
These are the symptoms and signs that suggest more serious diseases such as bowel cancer, colitis, Crohn’s disease or coeliac disease. These symptoms call for medical tests. If you have such symptoms, you should see your doctor. The most likely diagnosis may still be irritable bowel syndrome simply because it is so common (irritable bowel syndrome affects 10–20% of people, whereas the lifetime risk of bowel cancer is only 4%, or 1 in 25 people). Even so, because bowel cancer is one of the more treatable cancers, any change in bowel habit in a person over the age of 50 is investigated.
I’ve had severe pain for years. The doctors have been useless. All they say is that they can’t find anything wrong. I’ve tried everything going and nothing helps. How can I be expected to live like this?
As you have had the pain for years and the doctors still can’t find anything wrong, this means that your pain is ‘functional’ – it arises out of normal function and does not signify any damage.
Consequently, tests looking for damage from inflammation, cancer, infection, etc. will always be negative. Because you have lived with this for years, you will probably go on living with it for years. If you have really tried ‘everything going’ and no doctor or alternative practitioner has helped you, maybe you should work towards accepting your symptoms rather than pursuing a fruitless search for a cure. Save your energy for those parts of your life that are going well. There are many people with ongoing symptoms and disabilities of one sort or another that medicine – conventional or complementary – cannot significantly help. No one has died of irritable bowel syndrome, and life does go on.
Alarm Symptoms Suggesting That The Diagnosis May Not Be Irritable Bowel Syndrome (IBS)
* Bright red blood suggests that the bleeding is from the lower part of the bowel on the left side of the abdomen.
* Blood only on the outside of the stool is likely to be from the rectum
* Blood mixed in with the stool has come from higher up in the bowel
* Darker blood is blood that is partially digested so must be coming from higher up in the bowel
* Shiny, loose, tarry black stools are called ‘melaena’. This is blood digested by acid and intestinal juices, and is most likely to have come from the stomach or duodenum
* Although benign conditions such as piles probably account for 90% of bright red rectal bleeding, people who get this symptom should see their doctor to exclude more serious problems
Occasionally, people with irritable bowel syndrome lose weight because they eat less to avoid symptoms induced by their meals. Weight loss is also a common feature of depression.
This is definately not a feature of irritable bowel syndrome
This is more likely to be due to a structural stomach problem.
Fever suggests inflammation or infection
Night-time symptoms, disturbing sleep or waking the person from sleep
These are unusual in irritable bowel syndrome
Recent travel to areas widespread with infective gut disease or recent travel
Infection with an organism called Giardia is fairly common, and the symptoms are frequently prolonged.
Diarrhoea can be caused by a huge range of problems and it is often worthwile investigating this.
A family history of bowel cancer, Crohns disease, ulcerative colitis or coeliac disease.
* One first-degree relative (parent, brother or sister) with cancer, Crohn’s disease, bowel cancer doubles your risk of developing it too.
* Having a first-degree relative with inflammatory bowel disease or coeliac disease gives you about a 10% risk of getting that disorder.
But there must be something else to try?
You’re probably right! When people say they have tried everything, it is often more a statement of their frustration than of their actual experience. It is worth making a list of what you have tried, for how long, at what dose and in what circumstances. It may be worth trying some of these treatments again, perhaps in combination. An experienced doctor will probably have several suggestions to make based on your previous experience and your current symptoms. Moreover, new drugs and techniques to deal with irritable bowel syndrome will hopefully be increasingly available in the coming years.
• Acute and chronic pain are different.
• The pain of irritable bowel syndrome is usually associated with a change in bowel habit.
• The pain of irritable bowel syndrome does not represent physical damage. It should be thought of as a signalling problem between the gut and the brain.
• In irritable bowel syndrome there should be no ‘alarm’ symptoms (e.g. bleeding, anaemia, weight loss or night-time symptoms).
• Simple analgesics like paracetamol or ibuprofen do not usually work in irritable bowel syndrome.
• Antispasmodics or smooth muscle relaxants can work, and usually without side effects.
• Low-dose amitriptyline is probably the most effective drug currently available for pain in irritable bowel syndrome.
• New drugs are being developed, but their availability is still restricted because of worries about serious side effects.