Differences between NSAIDs (Non-opioid) and Opioid Analgesics

Based on "Essential Pain Pharmacology"
written by Howard S. Smith MD, Marco Pappagallo MD

There are two primary types of analgesics: narcotic (opioid) and non-narcotic (nonopioid) analgesics.

NSAIDs vs  Opioids

Primary differences at a glance:

Non-Narcotic Analgesics Narcotic Analgesics
Act peripherally Act centrally
Not habit-forming Addiction, dependence, tolerance
Not controlled drugs Schedule II/III controlled substances
Notable adverse effects: gastric irritation, bleeding problems, renal toxicity Notable adverse effects: sedation, respiratory depression, constipation
Anti-inflammatory effect No anti-inflammatory effect
Ceiling effect - increase in dose does not increase analgesia but increases side effects No ceiling effect

Opioid (narcotic) analgesics are derived from or related to the Opium. They bind to opioid receptors, which present in many regions of the nervous system and are involved in pain signaling and control. There are four groups of opioid receptors: delta, kappa, mu, and sigma.

Non-onopioid (non-narcotic) analgesics include acetaminophen, the most commonly used over-the-counter pain medicine. Other drugs are not technically part of the analgesic family, but are nonetheless considered analgesics in practice. These include nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin and acetaminophen are two of the most widely used analgesics and are effective for mild to moderate headache and pain of musculoskeletal origin.

Mechanism of Action

Opioid analgesics relieve pain by acting directly on the central nervous system. Opioids are unique in that they not only block the transmission the incoming painful stimuli to the brain but also act at higher brain centers, controlling the affective components of the pain.

Non-opioid analgesics have principally analgesic, antipyretic, and anti-inflammatory actions. The mechanism of action of traditional NSAIDs involves blockade of the production of prostaglandins by inhibition of the enzyme cyclooxygenase (COX) at the site of injury in the periphery, thus decreasing the formation pain mediators in the peripheral nervous system.

Nonopioids act primarily in peripheral tissues to inhibit the formation of pain-producing substances such as prostaglandins. They do not bind to opioid receptors and are not classified under the Controlled Substances. They are milder forms of the painkillers.



Opioid analgesics are more effective than NSAIDs in providing pain relief.

NSAIDs provide effective relief of many types of acute and persistent pain, especially associated with inflammation. Prescribed alone, these agents can relieve slight to moderate pain. Alternatively, for moderate to severe pain, they can be used in combination with opioids to enhance pain relief.

Opioids are much stronger and are used when pain signals are too severe to be controlled by non-narcotic analgesics.

The primary difference has to do with how drugs produce their analgesic effects. The opioids reduce pain by working on special pain receptors in the nervous system, primarily located in the brain and spinal cord. Three main types of opioid receptor are mu, delta and kappa.

The non-opioids, on the other hand, work more directly on injured body tissues. The opioids decrease the brain's awareness of the pain, whereas the non-opioids affect some of the chemical changes that normally take place wherever body tissues are injured or damaged. These chemical changes at the site of the injury typically result in inflammation and increased pain sensitivity.

Risks & Side Effects

The long-term use of opioids can lead to tolerance and necessity of dose escalation. Tolerance occurs when chronic exposure to a drug results in diminished antinociceptive or analgesic effect, so the larger doses are necessary to achieve the same degree of analgesia.

However, tolerance is not considered to be a problem by most pain specialists. Many persons with chronic pain who are taking opioids are able to maintain their dosage level without continuing escalating.

Physical dependence is usually an inevitable consequence of taking opioids over prolonged time. Physical dependence is apparent when a patient abruptly stops taking the drug or reduces the dosage. This leads to withdrawal reactions. Physical dependence is not the same as addiction and is not considered to be a problem by most pain specialists.

Although non-opioids are often preferred for most types of chronic pain, they have two serious drawbacks. The first drawback has to do with ceiling effects. Non-opioids have upper limit of pain relief that can be achieved. Once that upper limit or ceiling is reached, increasing the dosage will not provide any further pain relief. Opioids, on the other hand, tend not to have a ceiling effect. That is, the more you take, the more pain relief you will get. That is the reason why non-opioids are effective only for mild to moderate pain, whereas opioids are useful for more severe pain intensity.

The second major drawback of the non-opioids is adverse effects on various organ systems. Although most non-opioids are quite safe when used for temporary acute pain, problems may arise when people take them over a long period of time (for chronic pain). This is especially true when large quantities of non-opioids are taken. Most are aware of the adverse effects on the gastrointestinal system. However, excessive use of the non-opioids can also damage the liver or kidneys.

Opioids have a long list of possible side effects as well. However, it is interesting that many pain specialists now believe that opioids, when used properly, are often safer than the non-opioids.

Opioids produce respiratory depression. They reduce respiration by decreasing both the sensitivity of the medulla to carbon dioxide concentrations and the respiratory rate. Other side effects of the opioids include dizziness, nausea, vomiting, constipation, pruritus, sedation, mental clouding, and miosis4. Many of these side effects can be minimized or eliminated with proper medical management.

Non-opioid agents differ from opioid analgesics in several ways:

  • non-opioids have a ceiling effect in analgesia (a maximum dose beyond which analgesic effect does not increase)
  • do not produce tolerance, physical dependence, or euphoria, and are not associated with abuse or addiction
  • they are antipyretic and all except acetaminophen are anti-inflammatory agents
  • the primary mechanism of action of non-opioid analgesics is inhibition of prostaglandin formation
  • opioids work within the central nervous system by acting on receptors located on neuronal cell membranes

Related resources

References & Resources

  • 1. Pasternak GW. Pharmacological mechanisms of opioid analgesics. Clin Neuropharmacol. 1993 Feb;16(1):1-18.
  • 2. Kay B. Narcotic analgesia--ceiling effect. Anesthesiology. 1985 Mar;62(3):371-2.
  • 3. Sandra P. Welch, Billy R. Martin. Modern Pharmacology with Clinical Applications. Chapter 26 Opioid and Nonopioid Analgesics.
  • 4. Labianca R, Sarzi-Puttini P, Zuccaro SM, Cherubino P, Vellucci R, Fornasari D. Adverse effects associated with non-opioid and opioid treatment in patients with chronic pain. Clin Drug Investig. 2012 Feb 22;32 Suppl 1:53-63 PubMed

Published: May 05, 2007
Last updated: August 27, 2019


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