Description of the condition
Acute pain is experienced from time to time by almost everyone and is defined as short-term pain of less than 12 weeks duration. It may be due to tissue damage or nerve injury, or both, as a result of injury (e.g. sprains and strains, falls), surgery, or to a temporary or intermittent 'malfunction' of a body system (e.g. dysmenorrhoea (period pain), constipation), or to some form of headache (e.g. tension headache). It is frequently a manifestation of inflammation and sometimes swelling, especially in joints and muscles. By definition, it is not expected to continue indefinitely, even if not treated, but it can have a significant impact on ability to function normally.
Studies to determine the efficacy of analgesics in acute painful conditions are most commonly carried out in patients who are experiencing postoperative pain. The methods have been standardised over many years and the study design has proved to be robust (McQuay 2012). Trials have to be randomised and double-blind. Typically, in the first few hours or days after an operation, patients develop pain that is moderate to severe in intensity, and will then be given the test analgesic (the intervention) or a placebo. Pain is measured using standard pain intensity scales immediately before the intervention and then afterwards using pain intensity and pain relief scales, usually over the following six hours. Pain relief of half the maximum possible pain relief or better (at least 50% pain relief) has become the standard outcome. For patients given rescue medication it is usual for no additional pain measurements to be made, and for all subsequent measures to be recorded as initial pain intensity or baseline (zero) pain relief (baseline observation carried forward). This process ensures that analgesia from the rescue medication is not wrongly ascribed to the test intervention.
Non-prescription analgesics for migraine headache will be covered in a different Cochrane review.
Description of the interventions
The aim is to try and assess relative efficacy of drugs like aspirin, paracetamol (acetaminophen), ibuprofen, diclofenac, naproxen, and other drugs alone, and in combinations with each other, with weak opioids like codeine, or with caffeine.
There is a bewildering variety of analgesics available without prescription in various parts of the world. They include paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) (such as aspirin and ibuprofen), and opioids (usually codeine), as well as numerous 'complementary therapies' and 'herbal' products. They may be available in different formulations, such as standard tablets, fast-acting tablets, effervescent powders, or liquids, and are frequently combined with each other, or with other products such as caffeine. Packaging and branding can make it difficult to identify similar products or to compare them.
Many of these analgesics can be bought from open shelves in pharmacies, supermarkets, and convenience stores, without any consultation with a doctor or checking by a pharmacist, while some are not displayed on open shelves and require some form of authorisation from a pharmacist before they can be sold. Regulations regarding the availability of these products vary between countries.
There are a number of websites that can provide information on analgesics available without prescription. In the UK this is the Proprietary Association of Great Britain (www.pagb.co.uk). For Europe, a searchable database is available from the European Self-medication Industry (www.aesgp.be), and for countries outside Europe at the website of the World Self-medication Industry (www.wsmi.org).
How the intervention might work
NSAIDs reversibly inhibit the enzyme cyclooxygenase (prostaglandin endoperoxide synthase or COX), now recognised to consist of two isoforms, COX-1 and COX-2, mediating production of prostaglandins and thromboxane A2 (Fitzgerald 2001). Prostaglandins mediate a variety of physiological functions such as maintenance of the gastric mucosal barrier, regulation of renal blood flow, and regulation of endothelial tone. They also play an important role in inflammatory and nociceptive (pain) processes. However, relatively little is known about the mechanism of action of this class of compounds aside from their ability to inhibit cyclooxygenase-dependent prostanoid formation (Hawkey 1999). Aspirin is a special case, in that it irreversibly blocks COX-1. It also has good antipyretic (fever reducing) properties.
Paracetamol lacks significant anti-inflammatory activity, implying a mode of action distinct from that of NSAIDs. Despite years of use and research, however, the mechanisms of action of paracetamol are not fully understood. Paracetamol has previously been shown to have no significant effects on COX-1 or COX-2 (Schwab 2003), but has recently been considered as a selective COX-2 inhibitor (Hinz 2008). Significant paracetamol-induced inhibition of prostaglandin production has been demonstrated in tissues in the brain, spleen, and lung (Botting 2000; Flower 1972). A 'COX-3 hypothesis' wherein the efficacy of paracetamol is attributed to its specific inhibition of a third cyclooxygenase isoform enzyme, COX-3 (Botting 2000; Chandrasekharan 2002; PIC 2008) now has little credibility and a central mode action of paracetamol is thought to be likely (Graham 2005).
Codeine is an opioid which is metabolised in the liver to the active compounds morphine and morphine-6-glucuronide. Opioids bind to specific receptors in the central nervous system (CNS), causing reduced pain perception and reaction to pain, and increased pain tolerance. In addition to these desirable analgesic effects, binding to receptors in the CNS may cause adverse events such as drowsiness and respiratory depression, and binding to receptors elsewhere in the body (primarily the gastrointestinal tract) commonly causes nausea, vomiting, and constipation. In an effort to reduce the amount of opioid required for pain relief, and so reduce problematic adverse events, opioids are commonly combined with non-opioid analgesics, such as paracetamol.
While there may be other components in some non-prescription analgesics, these are usually present infrequently, and at doses too low to have any major impact. An exception is caffeine, which has been shown to add to analgesic effects in acute pain, in conjunction with conventional analgesics, and at caffeine doses of 100 mg or above (Derry 2012).
Why it is important to do this overview
This review is intended to provide information to consumers about non-prescription oral analgesics for treating acute pain conditions like toothache, period pains, headache, or acute musculoskeletal problems like strains and sprains. Many products are available, but there is little information about their relative efficacy.
Scanning the pharmacy online databases will determine how many formulations are available to treat mild headache, joint and muscle pain, dental, back, and period pain. The amount of high quality information about the efficacy of these analgesics is limited. Although Cochrane reviews are intended for use by consumers as well as healthcare providers and commissioners, there is to date no overview that directly addresses consumer issues relating to acute pain treatments that can be obtained without a prescription and their effectiveness. The consumer is faced with a variety of different pain relieving medicines, at different amounts per tablet, sometimes alone and sometimes with other ingredients available; this makes choosing a product rather difficult for the consumer.
A broad range of analgesics is available without prescription in many parts of the world. This review is intended to cover most of the less costly analgesics available almost anywhere in the world.