Understanding the WHO Analgesic Ladder
The World Health Organization (WHO) first introduced the analgesic ladder in 1986 as a guiding framework for the management of cancer pain [1.2.2]. Its primary goal was to provide a simple, effective, and systematic approach for healthcare providers to relieve pain. The core principles of the ladder are often summarized as "By the Mouth, By the Clock, By the Ladder" [1.4.5]. This means medications should be administered orally whenever possible, given at regular intervals to maintain pain control, and escalated in intensity according to the ladder's steps based on the patient's pain level [1.4.5, 1.4.8]. The ladder is a three-step process designed to match the strength of the analgesic medication to the severity of the pain.
Step 1: Mild Pain
This initial step is for patients experiencing mild pain. The recommendation is to use non-opioid analgesics [1.4.5]. These medications typically include:
- Acetaminophen (Paracetamol) [1.4.6]
- Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), such as ibuprofen or aspirin [1.4.6]
At this stage, and indeed at every step, adjuvant medications can be added to the regimen [1.5.1]. Adjuvants are drugs that can enhance analgesic effects or treat concurrent symptoms that contribute to pain [1.4.8].
Step 2: Mild to Moderate Pain
If pain persists or progresses to a moderate level despite the use of Step 1 medications, the next step is to introduce a "weak" opioid [1.4.5]. These are often given in combination with the non-opioid analgesics from the first step [1.2.2].
Common weak opioids include:
- Codeine [1.2.2]
- Tramadol [1.2.2]
- Hydrocodone [1.2.2]
The use of non-opioids and adjuvant therapies can continue alongside these weak opioids to maximize pain relief [1.2.2]. There is some debate in the medical community about the necessity of this step, with some clinicians opting to move directly from Step 1 to low doses of strong opioids (Step 3) [1.2.7].
A Deep Dive into Step 3 of the WHO Analgesic Ladder
Step 3 represents the highest tier of the traditional WHO analgesic ladder and is reserved for patients suffering from moderate to severe pain that was not controlled by medications from the previous steps [1.2.1, 1.4.2].
Core Component: Strong Opioids
The cornerstone of Step 3 is the introduction of a strong opioid [1.2.2]. Unlike weak opioids, strong opioids generally have no "ceiling effect" for analgesia, meaning their pain-relieving effect can be increased by raising the dose, though this must be balanced against side effects [1.3.4]. Morphine has historically been the drug of choice for this step [1.2.4, 1.3.3].
Examples of potent opioids used in Step 3 include:
- Morphine [1.3.1]
- Oxycodone [1.3.1]
- Hydromorphone [1.3.1]
- Fentanyl [1.3.1]
- Methadone [1.3.1]
- Buprenorphine [1.3.1]
- Oxymorphone [1.3.1]
These medications are carefully titrated, meaning the dose is adjusted to achieve maximum pain relief with minimum adverse effects [1.3.3]. The choice of opioid may depend on individual patient factors, previous opioid exposure, and potential side effects [1.6.1].
The Role of Non-Opioids and Adjuvants in Step 3
A crucial aspect of Step 3 is that it does not replace the medications from Step 1. Instead, it builds upon them. A typical Step 3 regimen includes a strong opioid with or without non-opioid analgesics (like acetaminophen or NSAIDs) and with or without adjuvant therapies [1.2.2, 1.5.3]. This multimodal approach targets pain through different mechanisms, which can lead to better overall pain control and potentially lower required doses of opioids.
Adjuvant therapies become particularly important at this stage. These are drugs with a primary indication other than pain but which have analgesic properties in certain pain conditions. They can include [1.5.1]:
- Antidepressants (e.g., amitriptyline, duloxetine) for neuropathic pain.
- Anticonvulsants (e.g., gabapentin, pregabalin) for nerve-related pain.
- Corticosteroids (e.g., dexamethasone) to reduce inflammation and pain from nerve compression or bone metastases.
- Anxiolytics (e.g., diazepam) [1.4.8].
| Feature | Step 1 (Mild Pain) | Step 2 (Moderate Pain) | Step 3 (Severe Pain) |
|---|---|---|---|
| Pain Level | Mild | Mild to Moderate | Moderate to Severe [1.2.1] |
| Primary Medication | Non-opioid analgesics [1.4.5] | Weak opioids [1.4.5] | Strong opioids [1.4.5] |
| Examples | Acetaminophen, NSAIDs [1.4.6] | Codeine, Tramadol [1.2.2] | Morphine, Fentanyl, Oxycodone [1.3.1] |
| Use of Adjuvants | +/- Adjuvant [1.5.3] | +/- Non-opioid, +/- Adjuvant [1.5.3] | +/- Non-opioid, +/- Adjuvant [1.5.3] |
Modern Perspectives and a Fourth Step
While the three-step ladder has been highly effective, especially for cancer pain, its application to chronic non-cancer pain (CNCP) has been questioned [1.6.2]. Modern pain management has evolved, leading to proposed modifications. Some experts have suggested a revised four-step ladder [1.6.2, 1.6.3]. In some of these models, interventional therapies—such as nerve blocks, spinal cord stimulation, or epidural injections—are considered as a new Step 3 for patients who don't respond to weak opioids [1.6.2]. Strong opioids then become the final resort, or Step 4 [1.6.2]. These newer models emphasize a more holistic and interdisciplinary approach, integrating non-pharmacological therapies like acupuncture or physiotherapy at every stage [1.6.2, 1.7.3].
Conclusion
What is step 3 of the WHO analgesic ladder? It is the protocol's final and most potent stage for managing moderate to severe pain, primarily through the administration of strong opioids like morphine, fentanyl, and oxycodone [1.2.2]. This step is not performed in isolation; it integrates the continued use of non-opioid analgesics and adjuvant medications to achieve comprehensive pain control [1.5.3]. While originally designed for cancer pain, the principles of the ladder have influenced pain management across medicine, though modern adaptations now consider interventional techniques and a more individualized approach for chronic pain conditions [1.6.2].
For further reading, the WHO offers guidelines on the pharmacological management of cancer pain. An example can be found at the WHO's Institutional Repository for Information Sharing.
