Rationale for Administering Opioids in Moderate to Severe Pain
Strong opioids are the mainstay of analgesic therapy for moderate to severe pain because they provide effective pain relief through direct activation of opioid receptors in inhibitory pain circuits, with morphine serving as the first-line agent due to its proven efficacy, wide tolerability, ease of administration, and low cost. 1
Pharmacological Basis for Opioid Use
Opioids mediate analgesia by binding and activating receptors in both the peripheral nervous system and inhibitory pain circuits that descend from the midbrain to the spinal cord dorsal horn, producing dose-dependent pain relief. 2
The analgesic effect increases proportionally with increasing doses, allowing for individualized titration to achieve adequate pain control without an upper dose limit for most strong opioids. 1, 3
Evidence-Based Treatment Algorithm
When Pain Intensity is Moderate to Severe (≥4/10):
Non-opioid analgesics (acetaminophen, NSAIDs) alone are insufficient for moderate to severe pain, necessitating the addition of opioid therapy according to the WHO analgesic ladder. 1, 4
The WHO step-wise algorithm reserves opioid therapy specifically for moderate and severe pain, allowing clinicians to start directly at step 3 (strong opioids) when pain is very severe, rather than progressing through weaker opioids. 4, 2
Specific Starting Approach:
For opioid-naïve patients with moderate to severe pain, oral morphine 20-40 mg should be initiated immediately, or 5-10 mg IV/SC when urgent relief is needed or the oral route is unavailable. 1, 4
Analgesics must be administered on a regular schedule (not "as needed") for baseline pain control, with rescue doses (10-20% of total daily opioid dose) prescribed for breakthrough pain episodes. 1
Clinical Superiority Over Alternatives
Weak opioids (codeine, tramadol) have maximal daily dose limitations (360-400 mg) and lower relative effectiveness (0.1-0.2 compared to morphine), making them inadequate for severe pain. 1
Strong opioids have no upper dose limit, allowing unlimited upward titration until either pain control is achieved or intolerable adverse effects occur. 1, 3
Morphine has been the standard of care since 1977 in hospices and palliative care units, providing effective pain relief in the majority of patients with moderate to severe cancer pain. 1
Multimodal Enhancement Strategy
Combining opioids with non-opioid analgesics (acetaminophen 1000 mg every 4-6 hours, NSAIDs if not contraindicated) enhances overall analgesia while potentially reducing required opioid doses. 1, 4
Adjuvant analgesics should be added to either enhance the analgesic effect of opioids or counter adverse effects, optimizing the therapeutic window. 1, 5
Critical Management Principles
Route Selection:
The oral route is preferred when feasible, even for severe pain, as it is simple to administer and allows for stable dosing. 1
Parenteral routes (IV/SC) are reserved for patients requiring urgent relief, unable to swallow, or with poor oral tolerance, using a conversion ratio of 1:2 to 1:3 (oral to parenteral). 1, 4
Dose Titration:
Individual titration using immediate-release morphine every 4 hours plus hourly rescue doses for breakthrough pain is recommended, with assessment every 60 minutes for oral and every 15 minutes for IV administration. 1
Once pain is controlled with stable 24-hour requirements, conversion to extended-release formulations is appropriate for maintenance therapy. 1
Essential Prophylaxis
Laxatives must be routinely prescribed for all patients on opioids to prevent constipation, as this adverse effect does not develop tolerance. 1, 4
Antiemetics (metoclopramide or antidopaminergics) should be provided for opioid-induced nausea/vomiting, which typically resolves within days to weeks. 1, 4
Common Pitfalls to Avoid
Do not delay strong opioids for severe pain by attempting to use weak opioids first—the WHO ladder allows starting at step 3 when pain intensity warrants it. 4, 2
Do not use transdermal fentanyl for initial opioid titration, as it is only appropriate once pain is controlled with other opioids due to its slow onset and difficulty adjusting doses. 4, 5
Do not prescribe opioids "as needed" for continuous chronic pain—around-the-clock dosing is essential for baseline pain control, with separate rescue doses for breakthrough episodes. 1, 2
In patients with renal impairment (eGFR <30 mL/min), use fentanyl or buprenorphine instead of morphine, as morphine metabolites accumulate and cause toxicity. 1, 4
Quality of Life Impact
Opioids reduce pain intensity, increase functioning, and improve quality of life for prolonged periods in patients with severe pain for whom no other more effective and less risky therapy is available. 6
Uncontrolled moderate to severe pain markedly reduces quality of life, and the benefits of opioid therapy in achieving pain control outweigh the risks when properly managed with monitoring and prophylaxis. 3, 6