Pain Management and Nociception Quiz

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Questions and Answers

Which statement best describes the nature of pain?

Pain can only become chronic if it is associated with nociceptive processes.

Pain is solely a sensory experience without emotional aspects.

Pain always arises from immediate physical injury.

Pain is an unpleasant experience that can be linked to both actual and potential tissue damage. (correct)

What is the primary role of nociceptors in the pain experience?

To activate mechanisms that block pain transmission.

To process and interpret pain signals in the brain.

To enhance the perception of pain by amplifying signals.

To detect noxious stimuli that may cause tissue damage. (correct)

Which type of pain is characterized by damage to peripheral nerves?

Referred pain

Nociplastic pain

Neuropathic pain (correct)

Secondary pain

Which of the following medications is primarily used for managing nociceptive pain?

Opioids Signup and view all the answers

What is a significant social consequence of pain medication misuse?

Increased risk of addiction and related issues Signup and view all the answers

Which type of pain is characterized by being caused by damage to the nervous system?

Neuropathic pain Signup and view all the answers

Which symptom is classified as a positive symptom of neuropathic pain?

Spontaneous pain Signup and view all the answers

What differentiates nociplastic pain from other pain types?

It arises from altered nociception without clear evidence of peripheral activation. Signup and view all the answers

Which of the following describes acute pain?

Functions as a protective mechanism. Signup and view all the answers

What is an example of mixed pain?

Cancer pain Signup and view all the answers

What characterizes chronic primary pain?

It has no clear underlying cause or condition. Signup and view all the answers

Which of the following describes hyperalgesia?

Increased sensitivity to painful stimuli. Signup and view all the answers

What is the primary function of nociceptors?

To transmit pain signals due to tissue damage. Signup and view all the answers

Which type of pain is linked to an underlying condition?

Chronic secondary pain. Signup and view all the answers

Which of the following is an emotional response to pain?

Fear. Signup and view all the answers

What does the visual analogue scale measure?

The subjective intensity of pain. Signup and view all the answers

Which sensory experience is defined as 'pins and needles'?

Paresthesia. Signup and view all the answers

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

Attention and interpretation. Signup and view all the answers

What is the primary action of inflammatory mediators like prostaglandins and bradykinin?

They sensitize pain fibers. Signup and view all the answers

Which of the following medications is specifically classified as an irreversible NSAID?

Aspirin Signup and view all the answers

What is a key characteristic of COX II inhibitors compared to traditional NSAIDs?

Reduced risk of gastric ulceration. Signup and view all the answers

What is the main therapeutic use of paracetamol?

To reduce fever and alleviate pain. Signup and view all the answers

Which type of receptor is not one of the five main opioid receptors?

o (OOR) Signup and view all the answers

What is the mechanism of action for endogenous opioids on the neuronal level?

Reduce neurotransmitter release through Ca2+ channel inhibition. Signup and view all the answers

What is the role of enkephalinase in pain modulation?

Breaks down enkephalins and thus reduces their pain-relieving effect. Signup and view all the answers

Which of the following NSAIDs is known to have anti-pyretic properties?

Paracetamol Signup and view all the answers

What percentage of heroin addicts began their addiction with OxyContin?

78% Signup and view all the answers

Which medication is considered most effective for managing neuropathic pain?

Amitriptyline Signup and view all the answers

What is a common adverse effect of nerve block procedures when local anesthetics are used?

Seizures Signup and view all the answers

Which statement explains the pharmacological mechanism of gabapentanoids?

They bind to the a2d subunit of calcium channels. Signup and view all the answers

Why was Purdue Pharma sued for bad business practices?

For misrepresenting the addiction potential of OxyContin. Signup and view all the answers

What type of pain does Ciara experience after six months with no response to diclofenac?

Chronic non-specific pain Signup and view all the answers

What formulation did Purdue Pharma develop to deliver oxycodone effectively?

OxyContin Signup and view all the answers

What role do non-steroidal anti-inflammatory drugs (NSAIDs) play in nerve block procedures?

They mitigate inflammation in the nerve area. Signup and view all the answers

What is the primary reason why visceral pain is referred to areas far from the site of the stimulus?

Peripheral afferent neurons from viscera and skin converge on the same spinal neurons. Signup and view all the answers

Which neurotransmitter is NOT typically involved in pain neurotranmission?

Dopamine Signup and view all the answers

According to the gate control theory of modulation, what influences the modulation of pain perception?

Dorsal horn neuronal activity and emotional state Signup and view all the answers

In the context of visceral pain, what does the term 'dermatome' refer to?

A segment of skin supplied by a single spinal nerve. Signup and view all the answers

Which of these statements about pain modulation is true?

Pain can be suppressed during emergencies. Signup and view all the answers

What role does the NMDA receptor play in pain perception?

Facilitates the amplification of pain signals. Signup and view all the answers

Which type of neuron is primarily responsible for transmitting visceral pain to the spinal cord?

Primary afferent sensory neurons Signup and view all the answers

What substance is associated with the modulation of pain through the descending pathways?

Endocannabinoids Signup and view all the answers

What is the primary role of endogenous opioids in pain modulation?

They inhibit the release of certain neurotransmitters associated with pain transmission. Signup and view all the answers

Which neurotransmitter is primarily involved in the descending modulation of pain?

Serotonin Signup and view all the answers

Where are opioid receptors primarily located in the central nervous system?

Ubiquitously distributed in various regions Signup and view all the answers

What is the effect of cannabinoids like anandamide in the context of pain?

They reduce neurotransmitter release and attenuate nociceptive responses. Signup and view all the answers

What is a significant characteristic of the descending pain pathways?

They inhibit pain transmission through the release of serotonin and noradrenaline. Signup and view all the answers

Which type of receptor is activated by endocannabinoids to mediate pain relief?

Cannabinoid receptors Signup and view all the answers

In which area are the main types of opioid receptors found?

In both central and peripheral nervous systems Signup and view all the answers

What type of neuronal transmission do endogenous opioids primarily inhibit?

Release of substance P and glutamate at presynaptic sites. Signup and view all the answers

Which of the following medications is primarily indicated for chronic migraine prevention?

Erenumab Signup and view all the answers

Which mechanism of action is associated with Ubrogepant in the treatment of migraines?

Antagonism of the CGRP receptor Signup and view all the answers

Which of the following is NOT a type of migraine prophylaxis medication?

Ibuprofen Signup and view all the answers

What class of drugs does lasmiditan belong to in the context of migraine treatment?

5HT1F agonists Signup and view all the answers

Which medication is associated with chronic migraine only?

OnabotulinumtoxinA Signup and view all the answers

What is the recommended first-line pharmacotherapy for chronic low back pain when NSAIDs are ineffective?

Duloxetine Signup and view all the answers

Which demographic factors are associated with increased likelihood of prescription opioid use?

Older age, public insurance, and severe pain Signup and view all the answers

What type of pain is chronic low back pain classified as?

Nociplastic pain Signup and view all the answers

Which of the following best describes neurogenic inflammation?

Release of mediators from primary afferent C-fibres Signup and view all the answers

What is a potential serious side effect associated with the use of duloxetine?

Increased risk of suicidal ideation Signup and view all the answers

Which component of tramadol acts as an opioid receptor agonist?

(+)-tramadol Signup and view all the answers

What is the primary symptom associated with migraine as a result of neurogenic inflammation?

Nausea and visual disturbances Signup and view all the answers

When managing low back pain, which therapeutic approach is considered second-line treatment?

Prescription opioids Signup and view all the answers

What is the primary function of nalmefene?

To act as an opioid overdose treatment Signup and view all the answers

Which of the following correctly describes the half-life characteristics of naltrexone?

Long half-life used in standard opioid doses Signup and view all the answers

What is a significant challenge in treating overdose when xylazine is involved?

It does not respond to naloxone Signup and view all the answers

Which of the following statements reflects a key concern regarding opioid use in the U.S.?

Poverty is a main risk factor for addiction Signup and view all the answers

Methylnaltrexone, a peripherally acting antagonist, is specifically approved for which condition?

Opioid-induced constipation Signup and view all the answers

Which of the following is true about the opioid epidemic in the U.S. as of 2023?

The number predicted for opioid-related deaths was over 112,000 Signup and view all the answers

Which mechanism of action is NOT clearly associated with the therapeutic effects of naltrexone?

Causing pronounced hepatotoxicity Signup and view all the answers

What is the effect of using xylazine as an additive in opioid formulations?

Prolongs and enhances opioid effects Signup and view all the answers

What is a significant side effect of morphine that affects breathing?

Respiratory depression Signup and view all the answers

Which opioid agonist is over 100 times more potent than morphine?

Fentanyl Signup and view all the answers

What is the primary mechanism by which codeine alleviates pain?

Conversion to morphine Signup and view all the answers

What is one of the main reasons why novel opioids like nitazines are not clinically used?

Increased risk of respiratory depression Signup and view all the answers

Which receptor type does naloxone primarily act as an antagonist upon?

m receptor Signup and view all the answers

What is a characteristic effect of μ opioid receptor activation?

Euphoria in most individuals Signup and view all the answers

Which of the following side effects is directly related to morphine's action in the gastrointestinal tract?

Constipation Signup and view all the answers

How is the duration of action of morphine enhanced?

Using sustained release oral preparations Signup and view all the answers

Which opioid is specifically designed to prevent constipation while providing analgesic effects?

Targin (oxycodone + naloxone) Signup and view all the answers

What is an important diagnostic indicator of morphine overdose?

Miosis Signup and view all the answers

Which protein is NOT part of the CGRP receptor complex?

Serotonin transporter (SERT) Signup and view all the answers

Which of the following statements about migraine treatment is correct?

Triptans act as 5-HT1 agonists. Signup and view all the answers

What percentage of migraine attacks is associated with aura?

30% Signup and view all the answers

Which medication is classified as an ergot alkaloid in the context of migraine treatment?

Ergotamine Signup and view all the answers

What was the global prevalence of people affected by migraine in 2016?

1.04 billion Signup and view all the answers

Which receptor is NOT involved in the mechanism of action of sumatriptan?

5-HT2 Signup and view all the answers

Which is a key reason for the adverse effects of ergotamine?

It interacts with other 5-HT receptors and noradrenergic receptors. Signup and view all the answers

What is a significant problem associated with migraine treatment using sumatriptan?

It is very effective but also expensive. Signup and view all the answers

Study Notes

Course Information

Class: MED Y2
Module: CNS
Facilitator: Niamh Connolly ([email protected])
Facilitator: Dermot Cox ([email protected])
Date: 5th November 2024

Learning Outcomes I

Define and describe pain as a physiological and pathophysiological process
Describe the mechanisms of activation of nociceptors
Describe ascending pain pathways including specific, non-specific pathways, and areas of higher cortical processing
Describe pain modulation at the level of spinal cord and along descending pathways
Describe the different types of pain such as referred, primary, secondary, nociceptive, neuropathic and nociplastic

Learning Outcomes II

Outline the use of opioids and NSAIDs in nociceptive pain
Describe the role of a multi-disciplinary approach to managing nociplastic and chronic pain
Describe the mechanism of action and adverse effects of:
- drugs that target neuropathic pain
- drugs that control migraine
- local anaesthetics
- general anaesthetics
Describe the social consequences of misuse and over use of pain medication

Pain - Definition

"An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage"
Pain refers to noxious stimuli.
Pain is a normal response to injury
Primarily a protective mechanism, and can promote repair
Can become pathological, chronic
Pain is typically invoked by tissue damage (not always – e.g. neuropathic pain)

Types of Pain

Nociceptive pain: Pain caused by the activation of nociceptors, e.g., trauma
Neuropathic pain: Pain caused by damage (injury/disease) to the nervous system.
- Central, e.g., spinal cord injury, multiple sclerosis (MS)
- Peripheral, e.g., diabetic neuropathy, post-surgery neuropathic pain
- Negative symptoms: sensory loss, numbness
- Positive symptoms: spontaneous pain, increased pain sensation
- Deafferentation pain: occurs following peripheral nerve lesions such as phantom limb pain
Nociplastic pain (psychogenic pain): Persistent pain arising from altered nociception, despite no clear evidence of activation of peripheral nociceptors.
- Examples: Fibromyalgia, migraine
Mixed pain: Both nociceptive and neuropathic, e.g., cancer pain

Acute vs Chronic Pain

Acute pain (seconds): Experienced with real or potential tissue damage, appropriate protective mechanism
Sub-acute (hours-days): Associated with tissue damage and infiltration of immune cells, can promote repair
Chronic pain - pathological (months-years): Lasts longer than damage, neither protects nor supports repair, often requires treatment.
- Chronic primary pain: unclear underlying cause
- Chronic secondary pain: linked to an underlying condition

Multiple Responses to Painful Stimuli

Spinal withdrawal reflex
Conscious perception of pain
Autonomic nervous system (ANS) changes (e.g., increased alertness associated with pain)
Emotional responses (e.g., fear, depression, anxiety, hopelessness)
Pain behaviours (e.g., grimacing, limping, avoiding activities)

Perception of Pain

Pain perception has informational and motivational components (location, intensity, modality)
Pain perception can be altered, including hyperalgesia (increased sensitivity to painful stimuli) and allodynia (pain in response to non-noxious stimuli).
Past experience, attention, interpretation, and other contextual factors influence subjective pain experience

Clinical Characterisation of Pain

Sensations:
- Paresthesia: pins and needles
- Dysesthesia: burning sensation
Other clinical characteristics such as burning, stabbing, electric shock-like (nerve pain) and tenderness, achiness, and stiffness (muscle pain)

Clinical Characterisation of Pain - Visual Analogue Scale

Visual analogue scale (VAS) used to quantify pain experience

Pain Sensory Receptors = Nociceptors

Nociceptors: Free peripheral nerve endings of Aδ and C fibres that are excited by noxious or painful stimuli
Stimuli include mechanical (intense pressure or stretch), thermal (extremes of hot or cold), and chemical stimuli.
Chemical stimuli can cause or potentially cause tissue damage and release substances that either activate nociceptors directly or sensitize them.
Examples include bradykinin (BK), prostaglandins (PG), ATP, and H+.

Nociception = Transduction of Painful Stimuli

Detection of noxious stimuli by nociceptors
Transduction of electrical signal to the CNS

Pain Fibres (I & II)

Aδ fibres: Thinly myelinated fibres, speed of conduction ~5-35 m/s, trigger immediate withdrawal, produce sharp, localised, immediate pain
C fibres: Slow, unmyelinated fibres, speed of conduction 0.5-2.0 m/s, produce dull, diffuse pain (secondary pain), relay information via the thalamus to cortex, limbic system, and hypothalamus, and trigger memory of stimulus.

Pain Pathways

Conventional pathway is a 3-neuron system
Primary pain afferent to spinal cord, contralateral spinothalamic tract to thalamus, thalamus to sensory cortex
Sensory neurons from one side of the body project to the sensory cortex on the contralateral side
Pain from the face travels in cranial nerves (different pathways)

Nociceptive Fibres in Spinal Cord

Primary afferent neurons (Aδ and C fibres): transmit from nociceptor to the spinal cord via the dorsal root.
On entering the spinal cord, they ascend/descend in the tract of Lissauer.
Synapse with 2nd order neurons in superficial layers (laminae) of the dorsal horn.
- Aδ fibers – synapse in layers I and V (some synapse in layer II)
- C fibers – synapse in layer II (substantia gelatinosa)
2nd order neurons: Axons cross(decussate), ascend in contralateral spinothalamic tract, synapse with 3rd order neurons in thalamus.
3rd order neurons: axons project from thalamus to somatosensory cortex.

Ascending Pain Pathways (Specific & Non-Specific)

Specific pathways: relay information about a single type of stimulus to specific areas of the cerebral cortex involved in localization and pain perception.
Non-specific pathways: relay information from more than one type of sensory unit to the brainstem reticular formation and regions of the thalamus that are not part of the specific pathways. Involves behavioral responses.

Visceral Pain - Referred Pain

Visceral pain is poorly localized and felt in areas far away from the stimulus site.
Peripheral afferent neurons from viscera converge on the same spinothalamic neurons from the same spinal segment as skin afferents
Brain interprets visceral pain as coming from the area of skin that shares the same pathway.
Pain is referred to somatic structures, quite far from the internal organ.

Pain - Neurotransmission

Neurotransmitters involved in pain transmission include glutamate, NMDA, AMPA, and NK1 receptors.
Inhibitory neurons in the substantia gelatinosa use GABA, opioids, and endocannabinoids to modulate pain.

Modulation of Pain Perception

Pain perception can be magnified or suppressed (modulation).
Gate control theory: somatic non-painful signals can inhibit pain signal transmission.
Descending pathways influence dorsal horn modulation.
Endogenous opioids play a role.

Pain Modulation: Descending/Analgesic Pathways

Descending analgesic pathways modulate pain.
Periaqueductal gray matter and rostroventral medulla involved.
Endogenous opioid release from descending analgesic pathways bind with opioid receptors on afferent pain fibers inhibiting glutamate and substance p release.

Pain Modulation: Descending Control

Pain can be modulated by descending pathways originating from the brainstem (e.g., peri-ventricular/per-aqueductal grey matter, rostroventral medulla, including raphe nuclei and locus coeruleus)
Descending fibers reduce nociceptor transmission through neurotransmitters such as serotonin and noradrenaline.
Endogenous opioids and endocannabinoids also involved.

Endogenous Opioids

Neuropeptides associated with analgesic modulation (endorphins, enkephalins, dynorphins, endomorphins, orphanin-FQ/nociceptin)
Opioid receptors (μ, δ, κ) expressed in the dorsal horn.
Binding at presynaptic sites inhibits substance P and glutamate release; at postsynaptic sites, reduces depolarisation.

Endocannabinoids

Anandamide and 2-arachidonylglycerol (2-AG) mediate their analgesic effect via activation of cannabinoid receptors (CB1 and CB2).
Reduce neurotransmitter release, and attenuate nociceptive responses.

Clinical Characterisation of Pain- Visual Analogue Scale (VAS)

Visual analogue scale (VAS) used to quantify pain experience.

Case: Spinal Injury

Mark has a spinal injury and is experiencing neuropathic pain.
Management includes appropriate pain treatment strategy and consideration of appropriate medications.

Inflammatory Pain

Inflammatory mediators (e.g., prostaglandins, 5-HT, bradykinin) sensitize pain fibres.
They don't directly cause pain but sensitize fibres, increasing their response to pain signals

NSAIDs

Act to inhibit cyclooxygenase (COX) and prostaglandin (PG) production.
Are anti-inflammatory, analgesic, and anti-pyretic.
- Examples: Aspirin, ibuprofen, indomethacin

Anti-inflammatory Drugs

Inflammation is a major cause of pain
Due to specific inflammatory mediators sensitizing pain fibres.
Prostaglandins and calcitonin gene-related peptide primarily involved.

COXIBs

COX-II inhibitors (celecoxib, rofecoxib) developed for protection of gastric mucosa.
Have similar efficacy to non-selective inhibitors with reduced GI side effects (~50%).

Paracetamol

Technically not an NSAID; used for fever and pain (not inflammation).
Mechanism of action unclear but linked to COX II selective inhibition and its major metabolite NAPQI that activates TRPA1 in the spinal cord.

Opioid Analgesics

Opiate: compounds related to opium poppy (e.g., morphine)
Opioid: natural or synthetic compounds mimicking opiate-like effects