What is the endogenous pain analgesic system?

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Last updated: April 30, 2025View editorial policy

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From the Research

The endogenous pain analgesic system is a complex network of neural pathways and neurotransmitters that work together to inhibit pain signals, and its understanding is crucial for effective pain management, as evidenced by recent studies such as 1. The primary components of this system include the descending pain modulatory pathway originating in the brain, particularly the periaqueductal gray matter and rostral ventromedial medulla, which send inhibitory signals down to the spinal cord. These pathways utilize several key neurotransmitters including:

  • Endorphins
  • Enkephalins
  • Dynorphins (collectively known as endogenous opioids)
  • Serotonin
  • Norepinephrine
  • Gamma-aminobutyric acid (GABA) When activated, these chemicals bind to specific receptors that decrease the transmission of pain signals. The system can be triggered by various stimuli including:
  • Stress
  • Exercise
  • Acupuncture
  • Certain medications Understanding this system is crucial for pain management as many analgesic medications work by enhancing these natural pain-relieving mechanisms. For example, opioid medications mimic endorphins by binding to the same receptors, while some antidepressants increase levels of serotonin and norepinephrine to enhance descending inhibition of pain signals, as discussed in 2 and 3. Additionally, recent studies have shown that resolvins, a novel endogenous pain-inhibitory principle, have potent analgesic effects and may be a promising therapeutic target for pain management, as reported in 4. Furthermore, research on placebo analgesia has provided insights into the cognitive modulation of pain perception and the involvement of the endogenous opioid system, as discussed in 5. Overall, the endogenous pain analgesic system plays a critical role in modulating pain sensations, and its understanding is essential for the development of effective pain management strategies.

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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