Drugs
NSAIDs (such as Ibuprofen and Celebrex)
Greatly underestimated, these are particularly helpful in acute pain. They form the foundation upon which the effects of other drugs can build. For example, a therapeutic  dose of NSAIDs will double the effectiveness of every dose of morphine or codeine. They act at the periphery to reduce the inflammation associated with injury. When inflammation occurs, many toxins are released which leads to further inflammation and more pain. NSAIDs turn off an enzyme that promotes inflammation so reducing inflammation and therefore pain.
In the short term NSAIDS are generally well tolerated. The prescriber has to exercise caution when there is a history of heart disease, active gastric ulceration is an absolute contra-indication and diseased kidneys are a relative contra-indication. One area of common concern is patients with asthma. It is rare for asthmatics to be truly intolerant of anti-inflammatory drugs, and where intolerance does occur, the newer COX2 drugs are often well tolerated. Never say ‘never’! Just exercise due caution. If the source of the pain is constant patients will often benefit from a slow release preparation, either of one of the more modern COX2 specific drugs such as Celecoxib or of a more traditional drug such as Diclofenac. These, rather than providing 3 to 4 hours of pain relief will often give 10 to 12 hours: this is particularly useful when pain interrupts patients sleep.
In chronic disease the risk/benefit ration of NSAIDs is complicated by the risk of death from cardiac disease or gastric bleeding so it is increasingly rare for patients to take them indefinitely.
Paracetamol
For a thorough discourse on paracetamol see our review article linked here. Paracetamol is a rare drug in that it is remarkably benign and very effective. Generally loved by all, it, like NSAIDs, forms the bedrock of effective pain control. The main annoyance is that it is only really effective for 4 hours, the tablets are large and unpleasant to swallow and using them regularly requires 8 tablets a day. Roll on effective slow release paracetamol!
Lethal in overdose and almost completely harmless in therapeutic doses, obviously it requires respect, the main stumbling block is often persuading patients that you are actually doing something therapeutic by prescribing it!
Opiates
These come in many shapes and sizes, generally fantastic for short term control of acute pain. For some patients, although not without some clinical challenges, opiates can also be ideal for chronic pain control. The original therapeutic opiate is morphine. Like all opiates this works at the μ receptor in the dorsal horn of the spinal cord and in the brain. Not only does it reduce the intensity of the pain felt it also alters the emotional response to the residual pain, so that the subject cares less about their pain! Side effects are:
  • Psychological - Sleepiness, hallucinations, dependence
  • Respiratory - Reduced cough reflex, reduced response to Carbon Dioxide
  • Gastro-intestinal - Constipation, nausea
  • Other - Urinary retention, itchiness
These bother some patients and can be reduced by changing to other drugs within the same group. Oxycodone, fentanyl, buprenorphine or tramadol are often viable alternatives. Where the pain is less intense a small dose of codeine, dihydrocodeine or dextropropoxyphene can be added to the paracetamol in the form of a co-… preparation. There is rarely a role for the large doses of codeine or dihydrocodeine often seen used as the constipation is usually a major problem.
As the source of the pain is often constant, slow release preparation or patches are often preferable to immediate release preparations for effective background pain control, and these also often allow for a smaller overall dose of drug to be used. The dose should reflect the patient’s needs, which may be assessed when looking at requirements over 24 to 48 hours of a short acting opiate.  Once established, dosage rarely needs increasing, and weaning, when the time comes, can be done in a controlled and manageable way.
Tricylcics (Amitriptyline, Nortriptyline, Imipramine)
These are commonly used to treat pain when there is a neuropathic element to the pain. If the pain has a gnawing or lancing element to it, if it is associated with ischaemia or is visceral in origin they are often the first port of call. Reaching the correct therapeutic dose is often time consuming as there is often quite a small window between too low a dose with limited effect and too high a dose with excessive side effects. Having said that, they are the first port of call because they have the greatest chance of being effective.
Side effects are: drowsiness, dry mouth, blurred vision and constipation. The only one of these that commonly causes a problem is drowsiness. Because of this we generally start with a low dose (10mgs) taken in the evening and build up gradually from there. The effective therapeutic dose is very variable, in some it is 10mgs and others require 100mgs: a second agent may also need to be added in. Amitriptyline is the most commonly used drug but the others are preferable where side effects are a problem.
Anti-convulsants
Pregabalin and Gabapentin are now the only reliable anti-convulsants used for pain control. They are very similar in action: some patients tolerate one or other of them better. By and large they are both better tolerated that the tricyclics but are arguably less effective. If difficulty sleeping is a part of the disease process then tricyclics have a secondary advantage of helping with poor sleep patterns.
The side effects again limit the dosage, those commonly seen are dizziness, drowsiness and co-ordination problems. In Gabapentin use, beyond two thirds maximal dose there are diminishing returns with each increase in dose. On discontinuing these drugs many patients suffer with withdrawal phenomena, so cessation should be gradual.
SNRI’s
Selective Serotonin and Noradrenaline Re-uptake Inhibitors are like tricylcics; traditionally seen as anti-depressants. Unlike the SSRIs, SNRIs show some promise as pain control drugs and have an FDI licence for painful diabetic neuropathy amongst other things. Both Duloxetine and Venlafaxine have been used to good effect. Many clinicians see SNRIs as second only to tricyclics in neuropathic pain management. Side effects include nausea, sexual dysfunction and sweating. The dose used is generally smaller than the dose used to treat depression
Membrane Stabilisers
Traditionally mexiletine has been used to treat refractory pain. This however is a nasty drug! Permanent damage to the eyes is one of many side effects to consider. More recently transdermal lignocaine has found favour. This is a patch which can be cut and applied to the painful area for 12 hours at a time. It is particularly effective at treating regional pain syndromes and scar pain refractory to other drugs. Although expensive, apart from local skin reactions it is largely devoid of side effects. In clinical practice it appears to act in synergy with other treatments, although this is yet to be backed up by clinical trials.
Ketamine
Ketamine is a N-Methyl D-Aspartate (NMDA) receptor antagonist. It is traditionally used as an anaesthetic agent used in the third world and in the field. Ketamine acts through activation of glutamate receptors allowing for an influx of sodium and some calcium into cells. This process is thought to be important in the creation of plasticity in nerve cells.
Chronic pain often occurs when nerve cells not traditionally thought to transmit pain start to trigger a pain impulse: this is a manifestation of neural plasticity, so potentially NMDA is hugely important in the world of chronic pain.
Ketamine is associated with abnormal thoughts, hallucinations, a hypertensive reponse and rigidity. These side effects can occur when it is used to treat pain but generally they are seen at higher doses than those used in the pain clinic. It is a drug of abuse so it has to be used sensitively.
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