Physiology & management of pain
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Questions and Answers

Which of the following is a characteristic of NSAIDs? (Select one)

  • They inhibit cyclooxygenase and prostaglandin production (correct)
  • They act only as anti-pyretics
  • They are selective for COX II inhibition only
  • They have no analgesic effects

    • COX II inhibitors, such as celecoxib, were developed primarily to:

  • Increase the efficacy of pain relief
  • Protect against gastric ulceration (correct)
  • Enhance anti-inflammatory effects
  • Increase COX I activity

    • Which of the following is TRUE regarding paracetamol (acetaminophen)? A) It is primarily an anti-inflammatory drug B) It is classified as an NSAID C) Its mechanism of action is not fully understood, but it may involve COX II selective inhibition D) It has significant gastrointestinal side effects like NSAIDs

  • It is primarily an anti-inflammatory drug
  • It is classified as an NSAID
  • Its mechanism of action is not fully understood, but it may involve COX II selective inhibition (correct)
  • It has significant gastrointestinal side effects like NSAIDs

    • Which of the following compounds is an opioid analgesic?

    <p>Morphine</p> Signup and view all the answers

    Which of the following is a major inflammatory mediator that sensitizes pain fibers?

    <p>Prostaglandins</p> Signup and view all the answers

    What is the major difference between COX I and COX II inhibitors?

    <p>COX II inhibitors are developed to reduce gastrointestinal side effects</p> Signup and view all the answers

    Which of the following is NOT an opioid?

    <p>Ibuprofen</p> Signup and view all the answers

    Which of the following is a function of enkephalinase?

    <p>Breaks down enkephalins</p> Signup and view all the answers

    Thiorphan is an active metabolite of which drug?

    <p>Racecadotril</p> Signup and view all the answers

    Which of the following is a primary use of Thiorphan?

    <p>Anti-diarrheal</p> Signup and view all the answers

    Which opioid receptor type is NOT part of the classical five types?

    <p>s (SOR)</p> Signup and view all the answers

    Which of the following opioid receptors is primarily associated with pain control?

    <p>m (MOR)</p> Signup and view all the answers

    Opioid receptors are linked to which type of G-protein?

    <p>Gi</p> Signup and view all the answers

    Which of the following is a result of opioid receptor activation?

    <p>Opening of K+ channels</p> Signup and view all the answers

    Opioid receptors inhibit the opening of which channels to reduce neurotransmitter release?

    <p>Ca2+ channels</p> Signup and view all the answers

    Which of the following opioid receptors does morphine primarily act on?

    <p>μ (m), κ (k), and δ (d) receptors</p> Signup and view all the answers

    Which of the following is a common side effect of morphine?

    <p>Sedation and mental clouding</p> Signup and view all the answers

    Which opioid receptor is primarily responsible for euphoria in morphine use?

    <p>μ (m) receptor</p> Signup and view all the answers

    Which of the following side effects of morphine can be alleviated with an anti-emetic (dopamine receptor antagonist)?

    <p>Nausea and vomiting</p> Signup and view all the answers

    What is the half-life (t1/2) of morphine?

    <p>3 - 4 hours</p> Signup and view all the answers

    Which of the following is a typical route of administration for morphine?

    <p>Oral, subcutaneous, intramuscular, and intravenous</p> Signup and view all the answers

    Which opioid-related effect is marked by constriction of the pupils and is useful in diagnosing overdose?

    <p>Miosis</p> Signup and view all the answers

    Which of the following is a major mechanism by which morphine causes constipation?

    <p>Increased gastrointestinal muscle tone and decreased propulsive movements</p> Signup and view all the answers

    What is a characteristic feature of morphine administration in terms of its duration of action?

    <p>Sustained release preparations can prolong its action</p> Signup and view all the answers

    Which of the following is a primary characteristic of pethidine (meperidine)?

    <p>Less likely to cause constipation</p> Signup and view all the answers

    Codeine is primarily used for which of the following purposes?

    <p>Suppressing cough (antitussive)</p> Signup and view all the answers

    Which opioid agonist is 100 times more potent than morphine?

    <p>Fentanyl</p> Signup and view all the answers

    Which of the following is true regarding codeine?

    <p>It is converted to morphine in the body</p> Signup and view all the answers

    Targin is a combination of which two drugs?

    <p>Oxycodone and naloxone</p> Signup and view all the answers

    Which opioid agonist is commonly prescribed alongside paracetamol for its added analgesic effect?

    <p>Tramadol</p> Signup and view all the answers

    Which opioid agonist is specifically mentioned for its use in cancer pain management?

    <p>Fentanyl</p> Signup and view all the answers

    What is the main function of naloxone when combined with oxycodone in Targin?

    <p>To prevent constipation caused by oxycodone</p> Signup and view all the answers

    Which opioid agonist is primarily used for alleviating mild to moderate pain?

    <p>Tramadol</p> Signup and view all the answers

    Which of the following opioids is less likely to be abused due to its low efficacy and inability to be injected easily?

    <p>Codeine</p> Signup and view all the answers

    What is the primary structure of novel opioid nitazines?

    <p>Benzimidazole structure</p> Signup and view all the answers

    Which of the following is 1000 times more potent than morphine?

    <p>Etonitazene</p> Signup and view all the answers

    What is the main reason nitazines, such as etonitazene, are not clinically used?

    <p>Risk of respiratory depression</p> Signup and view all the answers

    What class of substances are nitazines, such as etonitazene, also known as?

    <p>Opioid New Psychoactive Substances</p> Signup and view all the answers

    Which of the following is true about naloxone? (Select all that apply)

    <p>It is used to reverse opioid overdose</p> Signup and view all the answers

    Why must naloxone be administered repeatedly in cases of opioid overdose?

    <p>It has a shorter half-life (1-2 hours) compared to morphine</p> Signup and view all the answers

    Which of the following is an approved use for naltrexone?

    <p>Treatment of opioid use disorder (OUD) and alcohol use disorder (AUD)</p> Signup and view all the answers

    What is a significant side effect of naltrexone?

    <p>Hepatotoxicity</p> Signup and view all the answers

    Which drug is specifically approved for opioid-induced constipation (OIC)?

    <p>Methylnaltrexone</p> Signup and view all the answers

    Which of the following statements is true about methylnaltrexone?

    <p>It is a peripherally acting opioid antagonist</p> Signup and view all the answers

    What is the primary mechanism of action of naltrexone in treating opioid use disorder (OUD)?

    <p>It blocks the μ receptor</p> Signup and view all the answers

    Which of the following is a characteristic of nalmefene compared to naloxone and naltrexone?

    <p>It has no hepatotoxicity and is approved for overdose treatment and AUD</p> Signup and view all the answers

    What is the main difference between naloxone and naltrexone in terms of their clinical uses?

    <p>Naloxone is primarily used to reverse acute opioid overdose, while naltrexone is used for long-term management of opioid and alcohol use disorders</p> Signup and view all the answers

    Nalmefene acts as a μ (mu) receptor antagonist and a κ (kappa) receptor partial agonist. Which of the following is true about its use?

    <p>It is approved for the treatment of alcohol use disorder (AUD)</p> Signup and view all the answers

    Nalmefene is used to treat alcohol use disorder (AUD). What is its mechanism of action in this context?

    <p>It blocks opioid receptors to reduce cravings and reward effects</p> Signup and view all the answers

    Which of the following is true about nalmefene compared to naltrexone? A) Nalmefene has a shorter half-life than naltrexone B) Nalmefene has a longer duration of action than naltrexone C) Nalmefene is used only for opioid overdose, while naltrexone is used for alcohol use disorder (AUD) D) Nalmefene is only available in injectable form, unlike naltrexone

    <p>Nalmefene has a shorter half-life than naltrexone</p> Signup and view all the answers

    Which of the following opioid antagonists is a peripherally acting antagonist used to treat opioid-induced constipation?

    <p>Methylnaltrexone</p> Signup and view all the answers

    What is the main action of xylazine in the central nervous system?

    <p>Acts as a α2-adrenergic receptor agonist</p> Signup and view all the answers

    Xylazine was initially developed as a treatment for:

    <p>Hypertension</p> Signup and view all the answers

    Which of the following is a street name for xylazine when used as an additive in opioids like fentanyl?

    <p>Zombie drug</p> Signup and view all the answers

    Xylazine enhances the effects of opioids. What makes treating overdose with xylazine challenging?

    <p>Xylazine is not reversed by naloxone</p> Signup and view all the answers

    Why is naloxone ineffective in reversing the effects of xylazine overdose?

    <p>Xylazine is not an opioid and does not interact with the opioid receptors</p> Signup and view all the answers

    Which of the following is a characteristic of neuropathic pain?

    <p>It is difficult to treat with conventional medications</p> Signup and view all the answers

    Gabapentinoids such as pregabalin and gabapentin primarily target which of the following?

    <p>High-voltage calcium channel accessory proteins</p> Signup and view all the answers

    How do gabapentin and pregabalin differ from GABA in terms of their mechanism of action?

    <p>They are analogues of GABA but do not act on GABA receptors</p> Signup and view all the answers

    What is the proposed mechanism by which gabapentinoids (pregabalin and gabapentin) relieve neuropathic pain?

    <p>By inhibiting calcium influx through voltage-gated channels</p> Signup and view all the answers

    What is the primary mechanism of action of local anesthetics (LAs) in nerve blocks?

    <p>Inhibition of sodium (Na) channels</p> Signup and view all the answers

    Local anesthetics (LAs) preferentially bind to which state of the sodium channel?

    <p>Open and inactivated states</p> Signup and view all the answers

    Which of the following is a common technique for performing a nerve block with local anesthetics?

    <p>Ultrasound-guided injection</p> Signup and view all the answers

    In addition to local anesthetics, which of the following can be included in a nerve block injection to enhance its effect?

    <p>NSAIDs or steroids</p> Signup and view all the answers

    Which of the following is a potential adverse effect of nerve blocks with local anesthetics (LAs)?

    <p>Seizures at high doses</p> Signup and view all the answers

    What was the main finding of the OPAL study regarding the use of opioids in managing low back/neck pain?

    <p>Opioids showed no clinical benefit compared to placebo</p> Signup and view all the answers

    What is the standard first-line therapy for chronic low back pain, which is an example of nociplastic pain?

    <p>Exercise therapy</p> Signup and view all the answers

    When managing nociplastic pain and if significant pain persists, which of the following therapies is recommended after exercise therapy?

    <p>Cognitive behavioral therapy (CBT) and mind-body interventions</p> Signup and view all the answers

    Which pharmacotherapy is recommended as a second-line treatment for nociplastic pain if exercise and mind-body interventions fail?

    <p>Duloxetine or tramadol</p> Signup and view all the answers

    When should NSAIDs be used in the treatment of chronic low back pain?

    <p>If they were effective in acute back pain</p> Signup and view all the answers

    What is the first choice of drug for patients with chronic low back pain who are non-responsive to NSAIDs?

    <p>Duloxetine</p> Signup and view all the answers

    What type of drug is Duloxetine?

    <p>Serotonin-norepinephrine reuptake inhibitor (SNRI)</p> Signup and view all the answers

    Which of the following is a significant risk associated with Duloxetine, especially in young people?

    <p>Suicidal ideation and suicide</p> Signup and view all the answers

    Tramadol is a racemic mixture of which two enantiomers?

    <p>(+) tramadol as a serotonin reuptake inhibitor, (-) tramadol as a norepinephrine reuptake inhibitor</p> Signup and view all the answers

    Which of the following actions does the (+) enantiomer of tramadol have?

    <p>Both A and C</p> Signup and view all the answers

    Which of the following is a potential risk of tramadol use?

    <p>Potential for dependence</p> Signup and view all the answers

    Amadol has a unique mechanism of action that involves which of the following?

    <p>Inhibiting serotonin and norepinephrine reuptake</p> Signup and view all the answers

    What is the risk associated with tramadol use in combination with other serotonergic drugs?

    <p>Serotonin syndrome</p> Signup and view all the answers

    What is the primary cause of neurogenic inflammation?

    <p>Release of inflammatory mediators from primary afferent C-fibers</p> Signup and view all the answers

    Which neuropeptide is primarily involved in neurogenic inflammation?

    <p>Calcitonin gene-related peptide (CGRP)</p> Signup and view all the answers

    What is the classic example of a condition involving neurogenic inflammation?

    <p>Migraine</p> Signup and view all the answers

    Which of the following describes the structure of the CGRP receptor complex?

    <p>Composed of two integral membrane proteins, CALCRL and RAMP1</p> Signup and view all the answers

    What is the function of the receptor coupling protein (RCP) in the CGRP receptor complex?

    <p>It links the CGRP receptor to the GαS protein</p> Signup and view all the answers

    Which of the following is a commonly used first-line treatment for acute migraine?

    <p>NSAIDs and/or paracetamol</p> Signup and view all the answers

    Which class of drugs is used to treat acute migraine by acting as 5-HT1 agonists?

    <p>Triptans</p> Signup and view all the answers

    Which of the following is NOT a triptan used for migraine treatment?

    <p>Ubrogepant</p> Signup and view all the answers

    Which of the following medications is a 5-HT1 agonist that is effective for treating acute migraine but should not be used in patients with coronary artery disease?

    <p>Ergotamine</p> Signup and view all the answers

    Which of the following medications is a CGRP antagonist used in the acute treatment of migraines?

    <p>Ubrogepant</p> Signup and view all the answers

    Which of the following is a 5-HT1F receptor agonist used for acute migraine treatment?

    <p>Lasmiditan</p> Signup and view all the answers

    What is the primary role of anti-emetics in the treatment of acute migraines?

    <p>To alleviate nausea and vomiting associated with migraines</p> Signup and view all the answers

    Which of the following treatments is commonly used for the prophylaxis of frequent migraines?

    <p>b-adrenoreceptor antagonists</p> Signup and view all the answers

    Which medication used in migraine prophylaxis is an antidepressant?

    <p>Amitriptyline</p> Signup and view all the answers

    Which medication is used in migraine prophylaxis but is specifically approved for chronic migraines?

    <p>OnabotulinumtoxinA (Botox)</p> Signup and view all the answers

    Which of the following is an anti-CGRP receptor antibody used in migraine prevention?

    <p>Erenumab</p> Signup and view all the answers

    What is the main mechanism of action of anti-CGRP antibodies in preventing migraines?

    <p>They inhibit CGRP receptors, preventing vasodilation and inflammation</p> Signup and view all the answers

    Which of the following types of pain is caused by damage to the nervous system?

    <p>Neuropathic pain</p> Signup and view all the answers

    Which of the following is an example of nociplastic pain?

    <p>Fibromyalgia</p> Signup and view all the answers

    Which type of pain results from altered nociception without clear activation of peripheral nociceptors?

    <p>Nociplastic pain</p> Signup and view all the answers

    Which of the following best describes mixed pain?

    <p>Pain arising from both nociceptive and neuropathic sources</p> Signup and view all the answers

    Which of the following is a characteristic of acute pain?

    <p>It is typically associated with real or potential tissue damage</p> Signup and view all the answers

    Chronic pain is typically defined as pain lasting for more than how long?

    <p>Months to years</p> Signup and view all the answers

    Which of the following is an example of chronic secondary pain?

    <p>Chronic low back pain due to an underlying condition</p> Signup and view all the answers

    Which of the following refers to an increased sensitivity to painful stimuli?

    <p>Hyperalgesia</p> Signup and view all the answers

    Which of the following terms describes pain in response to a non-noxious stimulus?

    <p>Allodynia</p> Signup and view all the answers

    Which of the following factors can influence the subjective experience of pain?

    <p>All of the above</p> Signup and view all the answers

    Which of the following is characterized by a 'burning' sensation in the skin?

    <p>Dysesthesia</p> Signup and view all the answers

    Which of the following best describes Aδ fibres?

    <p>Thinly myelinated fibres that conduct sharp, localized pain</p> Signup and view all the answers

    Which of the following is true about C fibres?

    <p>They are unmyelinated and conduct slow, diffuse pain</p> Signup and view all the answers

    Which pain fibres are responsible for transmitting dull, secondary pain and emotional responses?

    <p>C fibres</p> Signup and view all the answers

    Where do Aδ fibres relay information after detecting noxious stimuli?

    <p>Via the thalamus to the cortex</p> Signup and view all the answers

    Which pain fibres are involved in triggering an immediate withdrawal reflex?

    <p>Aδ fibres</p> Signup and view all the answers

    Which part of the brain is involved in processing the emotional response to pain transmitted by C fibres?

    <p>Limbic system</p> Signup and view all the answers

    C fibres are involved in transmitting pain signals to which of the following structures?

    <p>The thalamus, cortex, limbic system, and hypothalamus</p> Signup and view all the answers

    Where do Aδ fibres synapse in the spinal cord?

    <p>In layers I and V of the dorsal horn (some in layer II)</p> Signup and view all the answers

    Where do C fibres synapse in the spinal cord?

    <p>In the substantia gelatinosa (layer II)</p> Signup and view all the answers

    Which of the following accurately describes the pathway of primary afferent nociceptive neurons (Aδ and C fibers)?

    <p>They ascend or descend in the tract of Lissauer before synapsing in the dorsal horn</p> Signup and view all the answers

    What happens after the second-order neurons in the spinal cord synapse with primary afferent neurons (Aδ and C fibres)?

    <p>They cross (decussate) the spinal cord and ascend in the contralateral spinothalamic tract</p> Signup and view all the answers

    Which structure do third-order neurons in the spinothalamic tract project to?

    <p>Somatosensory cortex</p> Signup and view all the answers

    Where is the tract of Lissauer located, where primary afferent nociceptive neurons ascend or descend?

    <p>White matter of the spinal cord</p> Signup and view all the answers

    Substance P primarily acts on which receptor to modulate pain transmission?

    <p>NK1 receptor</p> Signup and view all the answers

    Which of the following molecules is involved in pain modulation through endocannabinoid (eCB) pathways?

    <p>Endocannabinoids</p> Signup and view all the answers

    According to the gate control theory of pain modulation, what role do large-diameter Aα and Aβ fibers play?

    <p>They stimulate interneurons that inhibit pain transmission.</p> Signup and view all the answers

    In the gate control theory, what is the function of interneurons in the dorsal horn's substantia gelatinosa?

    <p>They inhibit pain transmission between the first and second-order neurons.</p> Signup and view all the answers

    Which neurotransmitters are released by stimulated interneurons in the substantia gelatinosa to modulate pain?

    <p>GABA and Endogenous opioids</p> Signup and view all the answers

    Which of the following is the origin of descending pain-modulating pathways?

    <p>Rostroventral medulla and raphe nuclei</p> Signup and view all the answers

    What is the role of descending analgesic pathways in pain modulation?

    <p>They inhibit pain transmission by releasing endogenous opioids and neurotransmitters like serotonin and noradrenaline.</p> Signup and view all the answers

    Which of the following neurotransmitters are involved in descending pain modulation pathways?

    <p>Serotonin and Noradrenaline</p> Signup and view all the answers

    How do endocannabinoids mediate their analgesic effect?

    <p>By reducing neurotransmitter release from the presynaptic neuron.</p> Signup and view all the answers

    Which cannabinoid receptors are involved in pain modulation via endocannabinoids?

    <p>CB1 and CB2 receptors</p> Signup and view all the answers

    Where are CB1 receptors, involved in pain modulation, primarily expressed?

    <p>Brain and spinal cord</p> Signup and view all the answers

    CB2 receptors, involved in pain modulation, are predominantly expressed in:

    <p>Immune cells</p> Signup and view all the answers

    In the gate control theory, how do non-painful somatic signals inhibit pain transmission?

    <p>By activating inhibitory interneurons in the dorsal horn.</p> Signup and view all the answers

    What best describes the process of pain modulation?

    <p>Alteration of pain perception by various physiological mechanisms</p> Signup and view all the answers

    Which fibers are primarily responsible for inhibiting pain transmission according to Gate Control Theory?

    <p>Aα and Aβ fibers</p> Signup and view all the answers

    Which neurotransmitters are released by interneurons to inhibit pain transmission?

    <p>GABA and endogenous opioids</p> Signup and view all the answers

    Which key structure is involved in descending pain modulation?

    <p>Peri-aqueductal gray (PAG)</p> Signup and view all the answers

    Which neurotransmitter is NOT typically involved in descending pain modulation pathways?

    <p>Glutamate</p> Signup and view all the answers

    How do endogenous opioids, like endorphins, exert their analgesic effect?

    <p>Activating opioid receptors on afferent pain fibers</p> Signup and view all the answers

    Which receptors do endocannabinoids, like anandamide, bind to for pain modulation?

    <p>CB1 and CB2 receptors</p> Signup and view all the answers

    What function do descending analgesic pathways primarily serve in pain modulation?

    <p>Block the transmission of pain signals from the spinal cord to the brain</p> Signup and view all the answers

    What is the primary effect of the activation of CB1 receptors in pain modulation?

    <p>Inhibition of neurotransmitter release</p> Signup and view all the answers

    Which statement is true regarding the role of Aα and Aβ fibers in the Gate Control Theory?

    <p>They inhibit pain transmission by stimulating interneurons in the spinal cord</p> Signup and view all the answers

    How do endogenous opioids function in the context of pain modulation?

    <p>They bind to opioid receptors on afferent pain fibers to block pain signal transmission</p> Signup and view all the answers

    Which area of the brain is responsible for initiating descending analgesic pathways?

    <p>Peri-aqueductal gray (PAG)</p> Signup and view all the answers

    What is the function of endocannabinoids like anandamide in pain modulation?

    <p>Attenuating nociceptive responses by binding to CB1 and CB2 receptors</p> Signup and view all the answers

    Which neurotransmitter plays a role in inhibiting pain signals in the descending pain modulation pathway?

    <p>Serotonin</p> Signup and view all the answers

    What is the primary function of the substantia gelatinosa in pain processing?

    <p>To modulate pain transmission between first and second-order neurons</p> Signup and view all the answers

    Which pain fibers are primarily responsible for transmitting sharp, localized pain?

    <p>Aδ fibers</p> Signup and view all the answers

    What is a crucial action of descending analgesic pathways in the context of pain modulation?

    <p>Inhibiting the transmission of pain signals from the spinal cord to the brain</p> Signup and view all the answers

    What is the primary mechanism by which CB1 receptor activation influences pain perception?

    <p>Inhibiting neurotransmitter release to decrease pain perception</p> Signup and view all the answers

    Study Notes

    Pain Modulation

    • Pain modulation is the alteration of pain perception through various physiological mechanisms.

    Gate Control Theory

    • The Gate Control Theory suggests that pain transmission in the spinal cord can be modulated by the interaction of different types of nerve fibers.
    • Aα and Aβ fibers, which transmit non-painful sensory input, can inhibit pain transmission by stimulating interneurons in the spinal cord.
    • Interneurons release neurotransmitters, such as GABA and endogenous opioids, to inhibit pain transmission.
    • C fibers, which carry primary pain signals, are inhibited by the activity of Aα and Aβ fibers.

    Descending Pain Modulation

    • The descending analgesic pathways originate in the brain, particularly in the peri-aqueductal gray (PAG).
    • These pathways release neurotransmitters, such as serotonin, endorphins, and noradrenaline, to inhibit pain at the spinal cord level.
    • These neurotransmitters work by activating opioid receptors on afferent pain fibers, inhibiting the release of pain-related neurotransmitters like substance P, and modulating the activity of interneurons in the spinal cord.

    Role of Neurotransmitters in Pain Modulation

    • Endorphins: Endogenous opioids that activate opioid receptors on afferent pain fibers, reducing pain transmission.
    • GABA: Inhibitory neurotransmitter that reduces pain transmission by inhibiting the release of excitatory neurotransmitters.
    • Serotonin: Neurotransmitter released by descending pain modulation pathways to inhibit pain transmission at the spinal cord level.
    • Noradrenaline: Neurotransmitter involved in descending pain modulation pathways, contributing to pain reduction.
    • Endocannabinoids: Neurotransmitters, such as anandamide, that bind to CB1 and CB2 receptors to modulate pain.
    • Glutamate: Excitatory neurotransmitter involved in pain transmission, but not typically involved in descending pain modulation pathways.
    • Substance P: Neurotransmitter involved in transmitting pain signals from the periphery to the spinal cord.

    Key Structures Involved in Pain Modulation

    • Thalamus: Relay center for sensory information, including pain, to the cerebral cortex.
    • Spinal cord interneurons: Interneurons in the substantia gelatinosa modulate pain transmission between first and second-order neurons.
    • Peri-aqueductal gray (PAG): Brain region responsible for initiating descending analgesic pathways.
    • Substantia Gelatinosa: Region in the spinal cord where pain signals are modulated.

    Pain Fibers

    • Aα and Aβ fibers: Large, myelinated nerve fibers that transmit non-painful sensory information, playing a role in inhibiting pain transmission.
    • Aδ fibers: Small, myelinated nerve fibers that transmit sharp, localized pain.
    • C fibers: Small, unmyelinated nerve fibers that transmit dull, aching pain.

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