Module 2 Lecture 2: Lecture Treatment of Pain; Analgesics

Question 1

Question: What are some pharmacological interventions used to reduce pain?

Answer 1

Answer: Exogenous and endogenous compounds such as NSAIDs, local anesthetics, opioids, gabapentinoids, TCAs, SSRIs, and α2 agonists modulate the perception of pain.

Question 2

Question: What is the role of opioids in the modulation of pain?

Answer 2

Answer: Opioids bind to opioid receptors in the brain, brainstem, and spinal cord, inhibiting the release of pain neurotransmitters and increasing the inhibition of pain signals. They also activate descending inhibitory pathways that reduce the perception of pain.

Question 2

Question: How do NSAIDs and local anesthetics work to reduce pain?

Answer 2

Answer: NSAIDs reduce pain by inhibiting the production of prostaglandins, which are mediators of pain and inflammation. Local anesthetics block nerve signals by inhibiting sodium channels in nerve endings.

Question 3

Question: How do gabapentinoids help in reducing pain?

Answer 3

Answer: Gabapentinoids inhibit calcium channels on nerve cells, reducing the release of neurotransmitters involved in pain signaling, particularly in the dorsal horn of the spinal cord.

Question 4

Question: What are endogenous opioids and how do they function?

Answer 4

Answer: Endogenous opioids, such as enkephalins, endorphins, and dynorphins, are naturally occurring peptides that bind to opioid receptors to reduce pain by inhibiting neurotransmitter release and modulating pain pathways in the central nervous system.

Question 5

Question: What role do descending inhibitory pathways play in pain perception?

Answer 5

Answer: Descending noradrenergic and serotonergic fibers inhibit pain transmission in the spinal cord, reducing the intensity of pain signals reaching the brain.

Question 6

Question: What are the main opioid receptors, and what are their functions?

Answer 6

Answer: The main opioid receptors are:
μ receptor: Responsible for analgesia, euphoria, sedation, and respiratory depression.
δ receptor: Contributes to analgesia, especially in the periphery.
κ receptor: Involved in spinal analgesia, sedation, and dysphoria.

Question 7

Question: Describe the opioid pathways involved in pain modulation.

Answer 7

Answer: Opiates activate neurons in the periaqueductal grey (PAG = brain region) and nucleus reticularis paragigantocellularis (NRPG = part of brain, brainstem region), which project to the rostral ventral medulla (RVM = brain) including the nucleus raphe magnus (NRM = brain). These pathways release serotonin and enkephalins in the dorsal horn, inhibiting pain transmission.

Question 8

Question: What are some examples of exogenous opioids, and how are they used?

Answer 8

Answer: Exogenous opioids include morphine and synthetic derivatives like heroin. They are used to manage acute pain by binding to opioid receptors in the central and peripheral nervous systems.

Question 9

Question: What are NSAIDs and what are they commonly used for?

Answer 9

Answer: NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) are the most commonly used drugs for treating mild to moderate pain. They include drugs like aspirin, ibuprofen, diclofenac, and celecoxib.

Question 10

Question: How do NSAIDs alleviate pain?

Answer 10

Answer: NSAIDs alleviate pain by reducing the production of prostaglandin E2, which decreases sensitization and reduces pain. They inhibit the cyclo-oxygenase (COX) enzymes, COX-1 and COX-2.

Question 11

Question: What are the therapeutic effects of NSAIDs?

Answer 11

Answer: NSAIDs have anti-inflammatory, anti-pyretic (reduce fever), and analgesic (pain relief) effects. However, paracetamol (acetaminophen) is an exception as it does not have anti-inflammatory properties.

Question 12

Question: For what conditions are NSAIDs commonly used to provide symptomatic relief?

Answer 12

Answer: NSAIDs provide relief from pain and swelling in chronic joint diseases like osteoarthritis and rheumatoid arthritis, acute inflammatory conditions like sports injuries, postoperative pain, menstrual pain, headaches, migraines, and fever.

Question 13

Question: What role does the arachidonic acid pathway play in the action of NSAIDs?

Answer 13

Answer: NSAIDs inhibit cyclo-oxygenases (COX-1 and COX-2) in the arachidonic acid pathway, which reduces the production of prostaglandins that are involved in pain and inflammation.
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Question 14

Question: What are some common side effects of NSAIDs?

Answer 14

Answer: NSAIDs can cause gastric irritation, affect renal blood flow, prolong bleeding by inhibiting platelet function, and increase the likelihood of thrombotic events like myocardial infarction, especially with COX-2 inhibitors.

Question 15

Question: What are local anesthetics derived from, and what are some commonly used local anesthetics?

Answer 15

Answer: Local anesthetics are derived from cocaine. Commonly used ones include lidocaine, procaine, and benzocaine.

Question 16

Question: How do local anesthetics work to alleviate pain?

Answer 16

Answer: Local anesthetics inhibit voltage-dependent Na+ channels in sensory neurons, blocking the channel and preventing the transmission of pain signals.

Question 17

Question: Where do local anesthetics bind to inhibit pain?

Answer 17

Answer: They bind to the Na+ channel at sites exposed to the lipid membrane, specifically to the inactivated state of the channel, creating a use-dependent blocker.

Question 18

Question: What causes congenital inability to perceive pain?

Answer 18

Answer: Mutations in NaV1.7 cause a complete loss of channel function. NaV1.7 is exclusively expressed by sensory neurons and is a potential target for pain treatment drugs.

Question 19

Question: What challenges are associated with chronic opioid treatments for neuropathic pain?

Answer 19

Answer: Chronic opioid treatments may not provide long-term pain relief, may lead to addiction, and contribute to the opioid crisis. Alternatives include gabapentinoids and antidepressants.

Question 20

Question: How do antidepressants aid in pain management?

Answer 20

Answer: Antidepressants inhibit serotonin and noradrenaline reuptake , increasing their concentrations/availability in synaptic cleft for a longer time, prolonged pain inhibiting effect. This enhances the inhibitory actions of 5HT in the dorsal horn, dampening pain signals.

Question 21

Question: How do gabapentinoids help in treating chronic neuropathic pain?

Answer 21

Answer: Gabapentinoids inhibit voltage-gated Ca2+ channels in the dorsal horn, reduce neurotransmitter release, and predominantly affect glutamatergic neurons to reduce excitatory output.

Question 22

Question: What are the main classes of analgesic drugs?

Answer 22

Answer: The main classes include NSAIDs, local anesthetics, opioids, gabapentinoids, and antidepressants. Both endogenous and exogenous chemicals can alleviate pain.