Pain and over-the-counter medication

Nociceptive pain is triggered by activation of nociceptors from injury or inflammation, signalling pain through the spinal cord to the brain. It is usually acute and resolves with healing. Neuropathic pain results from nerve damage, leading to abnormal signal processing, causing chronic, often persistent pain even after the original cause has resolved.

Chronic pain, can last for weeks, months, or years and is often associated with conditions like arthritis, neuropathy, or fibromyalgia. Nociplastic pain is caused by altered central nervous system processing without clear tissue or nerve damage. Seen in conditions like fibromyalgia, it involves increased central sensitivity to pain.1, 2, 3

Pain modulation involves excitatory (e.g., glutamate) and inhibitory (e.g., GABA, endorphins) neurotransmitters. Chronic pain often involves sensitisation, where neurons become hyper-responsive, leading to amplified pain, even with minimal or no new stimuli.1, 2, 3

Pain is one of the most common reasons people seek medical attention, and over-the-counter (OTC) analgesia are frequently used for a wide range of mild to moderate pain conditions. Understanding the type and source of pain is important when choosing analgesia.4, 5, 6

Two primary classes of OTC pain relievers are nonsteroidal anti-inflammatory drugs (NSAIDs) and Paracetamol, each with distinct mechanisms of action, benefits, and risks. OTC pain relievers, including NSAIDs and paracetamol, provide accessible and effective options for managing various types of pain. However, they must be used carefully to avoid potential side effects and complications, especially in individuals with underlying health conditions.4, 5, 6, 7

NSAIDs are widely used for both pain relief and reducing inflammation, making them suitable for conditions like muscle strains, arthritis and menstrual cramps. Common NSAIDs available over the counter include ibuprofen, naproxen and aspirin. These drugs work by inhibiting cyclooxygenase (COX) enzymes, which play a key role in producing prostaglandins, chemicals responsible for pain, inflammation, and fever.4, 5, 6, 7

NSAIDs are generally effective for managing mild to moderate pain and are particularly useful for inflammatory conditions. However, they are not without risks. Prolonged use of NSAIDs can lead to gastrointestinal issues, including stomach ulcers and bleeding, due to their impact on the stomach’s protective lining. NSAIDs can also raise blood pressure and increase the risk of cardiovascular events, especially in individuals with a history of heart disease. Kidney damage is another potential side effect, especially for those who take high doses or have pre-existing kidney conditions.4, 5, 6, 7

Paracetamol is one of the most commonly used OTC pain relievers. Unlike NSAIDs, paracetamol does not contain anti-inflammatory properties, which makes it less effective for pain accompanied by inflammation.

However, it is generally effective as an analgesic and antipyretic and for managing headaches, toothache, and other non-inflammatory pain.

Paracetamol’s exact mechanism is not fully understood but is thought to work centrally, by inhibiting COX enzymes in the brain, and possibly through serotonergic pathways involved in pain modulation.4, 5, 6, 7

Although generally considered safe at recommended doses, paracetamol can be toxic to the liver in high doses. It is important to avoid exceeding the daily recommended dose, particularly because paracetamol is often an ingredient in combination medications for cold, flu, and allergy symptoms. Overdoses can occur inadvertently when individuals take multiple medications containing paracetamol, potentially leading to liver failure, which can be fatal in severe cases.4, 5, 6, 7

Combined products
Ibuprofen and paracetamol work to relieve pain in different ways. Combined in a precise formula, for example Easolief DUO, these medications can provide more effective and longer-lasting relief than either drug alone. Easolief DUO is clinically proven to provide 80 per cent more pain relief than the same daily dose of standard paracetamol alone.8 Easolief DUO also has faster onset of action than the equivalent OTC dose of ibuprofen alone; it acts over 15 per cent faster.8

With Easolief DUO you can reduce the daily pill intake for patients from 14 if alternating between paracetamol and ibuprofen, to only six tablets. The dosage regime is much simpler as patients only have to remember to take 1-2 tablets every six hours threetimes a day (not more than six tablets in any 24 hour period). This is more convenient and also helps avoid confusion and risk of over/under dosing. Another benefit of Easolief DUO is that it does not contain opiates.

Safety considerations and potential side-effects
When choosing an OTC pain reliever, it is important to weigh the potential benefits against the risks based on individual health factors and the type of pain being treated.

Certain populations, including older adults, pregnant women, and individuals with chronic conditions, may face higher risks from OTC pain relievers and should use these medications under medical guidance.4, 6, 9

Individuals with a history of gastrointestinal bleeding or stomach ulcers should exercise caution with NSAIDs, as they increase the risk of further gastrointestinal complications.

Those with kidney or liver disease should consult with a healthcare professional before using either NSAIDs or paracetamol, as both classes can worsen these conditions.

People with cardiovascular disease or high blood pressure should also approach NSAIDs cautiously, as these medications can increase the risk of heart attacks and strokes.4, 6, 9

Long-term use of any pain reliever, including OTC medications, can lead to a phenomenon known as medication-overuse headache, which is a chronic headache disorder caused by frequent use of pain relievers.

It is advisable to limit the use of OTC pain relievers to no more than two or three days a week, especially for headache management.4, 6, 9

To use OTC pain relievers safely, it is advisable to read and follow the label instructions, adhere to recommended dosages, and avoid combining multiple products containing the same active ingredient.

Consulting a healthcare professional is important, particularly if there is any uncertainty about dosage or if other medications are being taken that could interact with the pain reliever.

It is also important to inform healthcare professionals of any OTC pain reliever use during appointments, as these medications can influence the management of other health conditions.4, 6, 9

Specific types of pain
Musculoskeletal pain such as sprains, strains, and arthritis often respond well to NSAIDs due to their anti-inflammatory effects. Topical NSAIDs are also available and may provide localised relief with a lower risk of systemic side effects.1, 2, 4

Headaches and migraines: Paracetamol is commonly used for mild headaches, while NSAIDs are effective for tension headaches and some migraines. Combination products are also available and may provide enhanced relief for certain headaches.1, 2, 4, 6

Menstrual cramps: NSAIDs are often the preferred choice for menstrual pain because they address the underlying inflammatory process. Naproxen, in particular, may be beneficial due to its longer duration of action.4, 6

Neuropathic pain which can result from conditions like diabetes or shingles, is generally less responsive to OTC pain relievers. In these cases, prescription medications specifically targeting nerve pain may be more effective, although NSAIDs or paracetamol may offer some degree of relief for mild cases.4, 6

Future directions
Research into new OTC analgesics and more targeted pain relief approaches is ongoing. Recent studies have focused on individual responses to pain medication, as genetics and underlying conditions may influence efficacy and risk.

Efforts are also underway to develop NSAIDs with more selective COX-2 inhibition to reduce GI and cardiovascular risks.10

Non-pharmacological pain management techniques, including lifestyle modifications, physical therapy, and cognitive behavioural therapy, are increasingly being recognised as valuable, particularly for chronic pain.

Author
Theresa Lowry-Lehnen, RGN, PG. Dip Coronary Care, RNP, BSc, MSc, PG. Dip. Ed (QTS), M. Ed, PhD, Clinical Nurse Specialist and Associate Lecturer South East Technological University.

References:

1. 1. 1. Chen, J., Kandle, P., Murray, I., et al. (2024). Physiology, Pain. StatPearls Publishing. Available at: https://www.ncbi.nlm.nih.gov/books/NBK539789/
      2. Cao, B., Xu, Q., Shi, Y. et al. Pathology of pain and its implications for therapeutic interventions. Sig Transduct Target Ther 9, 155 (2024). https://doi.org/10.1038/s41392-024-01845-w
      3. Dydyk, A., Conermann, T. (2024). Chronic Pain. StatPearls Publishing. Available at: https://www.ncbi.nlm.nih.gov/books/NBK553030/
      4. Vordenberg, S. (2023). Oral Non-prescription Pain Medications for Adults. JAMA. 2023;330(9):886. doi:10.1001/jama.2023.11725
      5. Cusack, S., Lagali, A., and Stavrianos, A. (2021) ‘An Investigation into Over the Counter Painkiller Use,’ International Undergraduate Journal of Health Sciences: Vol. 1: Issue. 1, Article 7. https://doi.org/10.61862/2811-5937.1010 Available at: https://sword.cit.ie/iujhs/vol1/iss1/7
      6. Sissons, B. (2023). Which pain medications can a person purchase over the counter. https://www.medicalnewstoday.com/articles/over-the-counter-pain-meds
      7. Moore, R., Wiffen, P., Derry, S., Maguire, T., Roy, Y, Tyrrell, L. Non-prescription (OTC) oral analgesics for acute pain – an overview of Cochrane reviews. Cochrane Database Syst Rev. 2015 Nov 4;2015(11):CD010794. doi: 10.1002/14651858.CD010794. pub2. PMID: 26544675; PMCID: PMC6485506.
      8. Daniels et al. Maxigesic® 325 Acute Dental Pain Study
      9. Karłowicz-Bodalska. K., Sauer, N., Jonderko, L., Wiela-Hojeńska, A. (2023). Over the Counter Pain Medications Used by Adults: A Need for Pharmacist Intervention. International Journal of Environmental Research and Public Health. 2023; 20(5):4505. https://doi.org/10.3390/ijerph20054505
      10. FMI (2024). Over-the-Counter Pain Medication Market Outlook. Future Market Insights Inc. Available at: https://www.futuremarketinsights.com/reports/over-the-counter-pain-medication-market