Pain Pathways and Opiates Overview

Pain Pathways and Opiates

• Pain signals travel from free nerve endings to the spinal cord, then to the thalamus, and finally to the somatosensory cortex.
• Emotional and cognitive aspects of pain involve the hippocampus, amygdala, and cingulate cortex.
• Anti-pain pathways originate in the midbrain, using serotonin and norepinephrine to block pain signals.
• Opiates enhance the effects of these anti-pain pathways.

Opportunities to Decrease Pain

• Reducing inflammation (e.g., with aspirin, NSAIDs).
• Decreasing nociceptor excitation (e.g., gabapentin, pregabalin).
• Decreasing neurotransmitter release from nociceptors (e.g., opioids).
• Activating anti-pain pathways (e.g., antidepressants, opioids).
• Influencing cognitive and emotional responses to pain (e.g., opioids).

Terminology

• Opium: Juice extracted from the poppy plant.
• Narcotic: Any sleep-inducing drug, encompassing opiates.
• Opiate: A drug derived from opium (e.g., morphine, codeine).
• Opioid: An endogenous ligand that binds to opioid receptors (e.g., endorphins, enkephalins, dynorphins). "Opioid" now includes synthetic drugs acting on these receptors.

Opium Source and History

• Opium comes from the Papaver somniferum plant.
• Native to Eurasia.
• Used for thousands of years.
• Mixed with alcohol to create laudanum.
• Hypodermic injection in the 1800s contributed to the problem of addiction.

Opioid Functions and Synthesis

• Analgesia (pain relief)
• Sleep induction
• Cough suppression (anti-tussive)
• Regulating intestinal muscles.
• Produced from precursor polypeptides, cleaved into active forms by proteases.
• Endorphins from POMC
• Enkephalins from proenkephalin
• Endorphins and dynorphins from proendorphin

Opioid Receptors

• Metabotropic receptors (MU, KAPPA, DELTA)
• Areas where opioid receptors are: spinal cord, brainstem (respiration), thalamus, basal ganglia, nucleus accumbens, cortex.
• Endogenous Ligands include: endorphin, dynorphin, and enkephalin.
• Exogenous ligands include: morphine, naloxone, salvinorin A, pentazocine, kratom (partial mu agonist)

Opioid Drugs

Pure Mu Agonists

• Morphine, codeine, heroin, methadone, meperidine (Demerol)
• Fentanyl and derivatives are much more potent than morphine (80-500x).

Mu Antagonists

• Naloxone (Narcan): Reverses opioid overdoses.
• Naltrexone (ReVia, Trexan): Used for treatment to block the effects of heroin.

Partial Mu Agonists

• Buprenorphine (Subutex): Limits respiratory depression and abuse potential.
• Tramadol (Ultram): Inhibits norepinephrine reuptake, and releases serotonin, this extends the analgesic effect.

Mixed Agonist-Antagonists

• Pentazocine (Talwin): Analgesic, but dysphoria limit its usefulness.

• Suboxone: Buprenorphine + naloxone (the naloxone is inactive in the oral form)

Effects on Mu, Kappa, Delta Systems

• Mu: Analgesia, euphoria
• Kappa: Analgesia, dysphoria
• Delta: Analgesia, affect

Explore the complex pathways of pain transmission and the role of opiates in pain management. This quiz delves into the anatomy of pain signals, emotional impacts, and methods to decrease pain using various interventions. Understand critical terminology related to opiates, opioids, and pain relief mechanisms.