How do opiates work to relieve pain?

From the Guidelines

Opiates relieve pain by binding to specific receptors in the brain, spinal cord, and other parts of the body, primarily mu receptors, and should be used at the lowest effective dose for the shortest duration possible to minimize risks of respiratory depression, constipation, physical dependence, and addiction. These medications, which include morphine, oxycodone, hydrocodone, and fentanyl, attach to opioid receptors on nerve cells, blocking pain signals from reaching the brain and releasing dopamine, which creates feelings of pleasure and relaxation 1. When prescribed for pain, typical starting doses vary by medication: morphine (15-30mg every 4 hours), oxycodone (5-10mg every 4-6 hours), hydrocodone (5-10mg every 4-6 hours), or fentanyl (25mcg/hr patch changed every 72 hours) 1.

Key Considerations for Opiate Use

• Opiates work quickly for acute pain but carry significant risks, and their use should be carefully considered in the context of all pain management strategies, including non-opioid pain medications and nonpharmacologic treatments 1.
• The body develops tolerance over time, requiring higher doses for the same effect, and opioid use disorder is a significant concern, with an estimated 1.9 million persons abusing or dependent on prescription opioid pain medication in 2013 1.
• Non-opioid pain management strategies should be considered first or used alongside opiates when possible, and clinicians should consider the full range of therapeutic options for the treatment of chronic pain.

Important Risks and Side Effects

• Respiratory depression
• Constipation
• Physical dependence
• Addiction
• Opioid-induced ventilatory impairment (OIVI)
• Sleep-disordered breathing
• Hyperalgesia, which is defined as increased pain from a stimulus that normally provokes pain on supra-threshold stimulation, and has been demonstrated clinically and experimentally after withdrawal from opioids 1.

Recommendations for Use

• Use at the lowest effective dose for the shortest duration possible
• Close medical supervision
• Tapering plan when discontinuing to avoid withdrawal symptoms
• Consider non-opioid pain management strategies first or use alongside opiates when possible
• Carefully evaluate the risks and benefits of opioid use for each patient, considering their unique needs and circumstances.

From the FDA Drug Label

The principal therapeutic action of morphine is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with morphine Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. The precise mechanism of the analgesic action is unknown However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.

Opiates work to relieve pain by binding to opioid receptors in the brain and spinal cord, specifically the mu-opioid receptor. The exact mechanism of analgesia is unknown, but it is thought that these receptors play a role in the analgesic effects of the drug.

• Key points:
  • Opiates are full opioid agonists with no ceiling effect for analgesia.
  • Dosage is titrated to provide adequate analgesia, limited by adverse reactions.
  • Specific CNS opioid receptors are thought to play a role in the analgesic effects. 2

From the Research

Mechanism of Opiate-Induced Pain Relief

• Opiates work by binding to opioid receptors, which are found in various parts of the body, including the brain and spinal cord 3.
• This binding action triggers a response that reduces the transmission of pain signals to the brain, resulting in pain relief.
• Opioids can be considered broad-spectrum analgesic agents, affecting a wide number of organ systems and influencing a large number of body functions 3.

Interaction with Other Systems

• The use of gabapentinoids, such as pregabalin, has been shown to potentiate the effects of opioids on cyclic AMP signaling in neuropathic pain 4.
• However, the antiallodynic action of pregabalin in neuropathic pain is independent of the opioid system 5.
• Gabapentin has been found to enhance the analgesic effect of morphine in healthy volunteers, suggesting a pharmacodynamic and pharmacokinetic interaction between the two drugs 6.

Tolerance and Dependence

• The long-term use of opioids can lead to tolerance and dependence, which are significant concerns in pain management 3, 7.
• Tolerance occurs when the body adapts to the constant presence of opioids, requiring higher doses to achieve the same level of pain relief.
• Dependence can lead to withdrawal symptoms when opioids are discontinued, making it challenging to manage pain effectively.

Side Effects and Complications

• Common side effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression 3.
• Less common side effects may include delayed gastric emptying, hyperalgesia, immunologic and hormonal dysfunction, muscle rigidity, and myoclonus.
• Proper patient screening, education, and preemptive treatment of potential side effects can help maximize the effectiveness of opioids while reducing the severity of side effects and adverse events 3.