Lecture 2: Pain Systems

Question 1

what are nociceptors?

Answer 1

• specialized sensory nerve endings/receptors in the body responsible for detecting and transmitting signals related to potentially harmful/noxious stimuli (e.g. pain) to the CNS
• their specialized free nerve endings are in skin, muscle and viscera and cell bodies in the DRG
• Receptors at sensory terminals convert stimuli into electrical activity: the larger the change in voltage at the terminal, due to influx of Na+ & Ca2+ through receptors forming ion channels, the greater the number of APs generated

Question 2

what is nociception?

Answer 2

• neural process of encoding noxious stimuli
• physiologically composed of 4 processes: transduction, transmission, modulation & perception

Question 3

what is a noxious stimulus?

Answer 3

• a sensory input that has potential to cause tissue damage & liable to cause pain
• includes mechanical pressure, extreme temperatures, and exposure to irritating chemicals
• (nociceptors = specialized receptors that detect and respond to noxious stimuli)
• these stimuli perceived as pain when nociceptors send signals to CNS

Question 4

What factors can modulate pain perception?

Answer 4

• Past experiences
• Setting
• Affect (emotional + psychological factors)
• Cognitive influences
• Gender
• Cultural expectations

Question 5

Explain the Gate Control Theory of Pain (1965)

Answer 5

• Proposed by Melzack and Wall
• Small interneurons in the dorsal horn act as a gate.
• They control the excitation of transmission cells.
• Non-painful input “closes” the gate to painful input, preventing pain sensation from reaching CNS
• Stimulation by non-noxious input can suppress pain
• Provides a physiological explanation for psychological influences on pain perception
• Firing of projection neurons determines pain.
• Inhibitory interneurons in the dorsal horn decrease the chances of projection neuron firing.
• Firing of C fibers indirectly increases the chances of projection neuron firing.
• Stimulation of the periaqueductal gray matter activates enkephalin-releasing neurons that inhibit pain signals.

Question 6

What are the different types of nociceptors?

Answer 6

• mechanical nociceptors
• thermal nociceptors
• chemical nociceptors
• polymodal nociceptors (most abdundant)

Question 7

What are mechanical nociceptors, and what type of stimuli do they respond to?

Answer 7

• a type of nociceptive sensory receptor that responds to mechanical pressure, stretching, and deformation of tissues
• play a key role in detecting mechanical damage or injury

Question 8

Define thermal nociceptors and the specific stimuli they detect.

Answer 8

• specialized nociceptors that are sensitive to extreme temperatures
• they respond to very hot or very cold temperatures, alerting the body to potential tissue damage from thermal sources
• N.B. 10% of C-fibres signal innocuous thermal
  information

Question 9

Explain the function of chemical nociceptors and the substances they respond to.

Answer 9

• nociceptive sensory receptors that are activated by harmful chemicals and irritants
• respond to substances like acids, toxins, and inflammatory mediators, signalling the presence of potentially damaging chemicals

Question 10

What distinguishes polymodal nociceptors, and what types of stimuli can they respond to?

Answer 10

• versatile nociceptors that can respond to multiple types of noxious stimuli
• they integrate info from mechanical, thermal, and chemical sources, making them generalized detectors of potential harm

Question 11

what are the 4 processes of nociception

Answer 11

• transduction
• transmission
• modulation
• perception

Question 12

What is the definition of transduction in the context of nociception?

Answer 12

• initial step in nociception
• process by which specialized nociceptors convert harmful sensory input into electrical signals
• Nociceptors respond to mechanical pressure, temperature extremes, and chemicals by opening ion channels.

Question 13

How does the transduction process work in nociceptors?

Answer 13

• occurs at the peripheral level, where nociceptors detect noxious stimuli
• when specific types of stimuli, (e.g. mechanical pressure) encountered, nociceptors open ion channels.
• these are nonselective cation channels and voltage-gated Na+ channels
• when intensity of the stimulus reaches a certain threshold, nociceptors generate APs, which convey information about the noxious stimulus

Question 14

What does the process of transmission involve in nociception?

Answer 14

• the step where electrical signals generated by nociceptors are conveyed from the periphery to CNS
• pain signals travel along the axons of sensory neurons - specifically smaller-diameter unmyelinated C-fibers and larger-diameter myelinated A-delta fibers.
• A-delta fibers transmit sharp, fast pain signals, C-fibers transmit dull, slower pain signals
• these signals reach spinal cord, where they synapse with secondary neurons that further relay the info to higher CNS regions

Question 15

How do A-delta and C-fibers contribute to the transmission of pain signals?

Answer 15

• A-delta fibers transmit sharp & fast pain signals, providing a rapid response to noxious stimuli
• C-fibers transmit dull & slower pain signals, contributing to more sustained perception of pain
• secondary neurons in the spinal cord play a crucial role in transmitting pain signals to brain

Question 16

What is the process of modulation in nociception?

Answer 16

• occurs within CNS & involves enhancing or suppressing pain signals
• can influence perception of pain & intensity of pain experienced
• the spinal cord and higher brain centers play a role in modulation
• Inhibitory interneurons in the spinal cord can ↓ the likelihood of projection neurons firing, reducing pain perception.

Question 17

How can the firing of C-fibers impact pain modulation?

Answer 17

• can inhibit inhibitory interneurons in the spinal cord, indirectly increasing the likelihood of projection neurons firing
• this process can intensify pain perception & make pain experience more pronounced
• balance between excitatory & inhibitory processes in modulation is crucial in determining the overall pain experience

Question 18

What is the role of perception in the nociceptive process?

Answer 18

• final step in nociception, where brain processes & interprets pain signals received from spinal cord
• involves the conscious awareness of pain & the subjective experience of it
• considers factors like location, intensity, quality, & duration of pain.
• highly subjective & can be influenced by psychological, emotional & cultural factors.

Question 19

How can cognitive and emotional factors influence pain perception?

Answer 19

• can significantly impact pain perception
• brain evaluates info received from nociceptive signals & produces a subjective experience of pain
• Factors like past experiences, emotions, cultural expectations, & psychological states can all influence the overall perception of pain.
• can either amplify or diminish perception of pain

Question 20

How does the body’s endogenous analgesia system work?

Answer 20

• CNS & PNS possesses an endogenous analgesia system
• Pain can be modified by the periaqueductal gray (PAG) before reaching consciousness
• the central analgesia system involves the PAG, nucleus raphes magnus, and inhibitory neurons in the dorsal horn
• peripheral system includes various opioid receptors activated by endorphins.
• Endorphins are endogenous opioid inhibitory neuropeptides produced by the CNS and pituitary gland - they inhibit the release of substance P, reducing pain signals

Question 21

What are the three components of pain as described by Melzack and Casey (1968)?

Answer 21

• Sensory discriminative: Involves the sense of pain intensity, location, quality, and duration.
• Affective motivational: Pertains to the unpleasantness of pain & urge to escape it.
• Cognitive evaluative: Involves cognitive factors like appraisal, cultural values, distraction & hypnotic suggestions

Question 22

Define today’s pain definition and its components

Answer 22

• an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.
• components include sensory discriminative, affective motivational, and cognitive evaluative aspects of pain perception

Question 23

How is pain perception distributed in the brain?

Answer 23

• Pain matrix: A large brain network activated during acute pain experience.
• Specific areas include the anterior cingulate cortex (ACC), primary and secondary somatosensory cortex, insula, & others.
• Perception of pain intensity correlates strongly with the activation of multiple brain regions

Question 24

Explain pain hypersensitivity and its mechanisms.

Answer 24

• Pain hypersensitivity includes allodynia (lowered pain thresholds) and hyperalgesia (increased responsiveness to noxious stimuli).
• Mechanisms include peripheral sensitization (reduced threshold at the site of tissue damage) and central sensitization (increased excitability of neurons in the CNS).
  These mechanisms can be adaptive responses but may become maladaptive in chronic pain conditions

Question 25

How do psychological and social factors influence pain perception?

Answer 25

• Pain perception results from complex interaction of biological, psychological & social factors.
• Psychological processes can have biological effects - which can affect an individual’s psychosocial environment
• Coping strategies, e.g. catastrophizing, can significantly influence pain perception

Question 26

What transduction mechanisms are involved in mechanical nociceptors, and what is the proposed role of DmPiezo?

Answer 26

• Transduction mechanisms in mechanical nociceptors not been precisely identified
• but may involve transducer proteins related to the MDEG family found in invertebrates
• proposed role of DmPiezo in mechanical nociception has been suggested as a potential mechanism
• Additionally, nociceptive Schwann cells might play a role in this process (J Ojeda-Alonso et al., 2023).

Question 27

What is the stimulus and the underlying mechanism of nociceptive pain?

Answer 27

Stimulus: Nociceptive pain is triggered by actual or potential tissue damage.
Mechanism: arises from the activation of nociceptors

Question 28

What are the stimulus and mechanisms associated with inflammatory pain?

Answer 28

Stimulus: Inflammatory pain is initiated by the presence of inflammatory mediators.
Mechanisms: It involves both peripheral and central sensitization, leading to increased pain sensitivity in response to inflammatory chemicals.

Question 29

What stimulus and mechanisms are linked to neuropathic pain?

Answer 29

Stimulus: caused by nerve injuries, affecting both the PNS and CNS
Mechanisms: results from ectopic activity, loss of inhibitory mechanisms, & central sensitization, contributing to the development of chronic and often difficult-to-treat pain

Question 30

How can pain be classified based on its nature and impact on an individual’s well-being?

Answer 30

-nociceptive pain (resulting from actual or potential tissue damage) and clinical pain (encompasses a wider range of pain experiences).
- Another classification involves adaptive pain (serves a protective function) & maladaptive pain (may persist & become problematic)

Question 31

What role does the dorsal horn play in the modulation of pain processing?

Answer 31

• critical region in spinal cord that integrates peripheral, local & descending input related to pain
• changes in excitability at dorsal horn level play a vital role in controlling the transmission of pain signals to the brain
• acts as a crucial processing point where pain signals can be enhanced or inhibited, impacting the perception of pain

Question 32

What are the different states of processing in the dorsal horn, and how do they affect pain transmission?

Answer 32

four states of processing in the dorsal horn:
- State 1 (Normal): In this state, pain transmission operates normally without significant alterations.
- State 2 (Suppressed): Pain transmission is reduced or suppressed, resulting in decreased signal transmission.
- State 3 (Sensitized): Pain transmission is facilitated, often with short-duration effects.
- State 4 (Reorganized): Pain transmission becomes persistently facilitated, leading to long-term changes in signal transmission.

These states are plastic and state-dependent (i.e. can change & adapt based on various factors, impacting perception of pain)