Pain Modulation Pathway

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Questions and Answers

What is the primary function of the rostral ventromedial medulla (RVM)?

To facilitate the transmission of pain signals at the dorsal horn

To inhibit or facilitate the integration of pain at the dorsal horn (correct)

To modulate pain perception via the release of dopamine

To stimulate the release of substance P from presynaptic neurons

Which of the following brain regions transmits signals to the periaqueductal gray (PAG)?

Insula and amygdala

Hypothalamus and prefrontal cortex

Locus ceruleus and dorsal horn

All of the above (correct)

What is the primary mechanism by which the locus ceruleus modulates pain?

Stimulation of interneurons to release enkaphalin

Inhibition of substance P release from presynaptic neurons

Release of serotonin to inhibit pain transmission

Release of norepinephrine to inhibit pain transmission (correct)

What is the role of enkaphalin in pain modulation?

To inhibit the release of substance P from presynaptic neurons Signup and view all the answers

According to the Gate Theory, what is the primary mechanism by which pain is modulated?

Inhibition of the slower Aδ and C fibers by the faster Aβ fibers Signup and view all the answers

What is the primary source of the brain's norepinephrine which plays a role in inhibiting substance P?

Locus ceruleus Signup and view all the answers

Which of the following types of fibers respond to heat, mechanical, and chemical stimulation (polymodal) and travel via the dorsal medial leminiscal tract?

A-b fibers Signup and view all the answers

What is the result of nociceptor sensitization?

Increased pain sensations to painful stimuli Signup and view all the answers

What is the site of conscious pain?

Cerebral cortex Signup and view all the answers

What is the result of heterosynaptic activity-dependent plasticity?

Increased pain sensations to painful stimuli Signup and view all the answers

What is the main difference between hyperalgesia and heterosynaptic activity-dependent plasticity?

Hyperalgesia is a normal to protect from further injury, heterosynaptic activity-dependent plasticity is abnormal Signup and view all the answers

What is the main difference between direct activators and other neurotransmitters?

Direct activators contribute to pain by activating actual receptor, while indirect activators stimulate inflammatory cells to release chemical mediators (e.g. cytokines) Signup and view all the answers

What is the result of secondary hyperalgesia?

Increased pain sensations at the uninjured skin surrounding the original injury due to increased nociceptor signal transmission Signup and view all the answers

What is the primary function of the superficial dorsal horn (lamina I and II)?

Main target for C fibers Signup and view all the answers

Which of the following brain regions is responsible for processing the location and intensity of pain?

Somatosensory cortices (S1 and S2) Signup and view all the answers

What is the role of wide dynamic range neurons located in lamina V?

Modulation of pain intensity and integration of sensory information due to convergence of A-d and C fibers Signup and view all the answers

What is the function of cytokines in nociceptor sensitization?

Both direct and indirect activators of nociceptor sensitization Signup and view all the answers

What is the result of primary hyperalgesia, which is characterized by increased nociceptors' sensitivity at the injury site?

Increased pain sensitivity Signup and view all the answers

What is allodynia?

A type of neuropathic pain from a stimulus that usually would not cause pain Signup and view all the answers

What happens when inflammatory processes do not resolve in the pain pathway?

Sensitization leads to transition from acute to chronic pain Signup and view all the answers

What is the main difference between windup/secondary hyperalgesia and primary hyperalgesia?

Windup/secondary hyperalgesia involves increased signal transmission, while primary hyperalgesia involves increased sensitivity at the site of injury. Signup and view all the answers

What causes windup?

Accumulation of glutamate and substance P causing prolonged activation of NMDA receptors and therefore increased excitability of dorsal horn neurons Signup and view all the answers

What are common features of neuropathic pain?

Abnormal myelination/demyelination and axonopathy Signup and view all the answers

What is the correct description of lamina II and III?

Substantia gelatinosa Signup and view all the answers

What type of stimuli do C fibers respond to?

Heat and sustained pressure Signup and view all the answers

What is the main difference between convergent and divergent neurons in the pain modulation pathway?

Convergent neurons receive input from multiple sources, while divergent neurons send output to multiple targets. Signup and view all the answers

What is the role of descending monoaminergic (serotonin and norepinephrine) neurons in pain modulation?

Inhibitory neurons involved in descending pain modulation Signup and view all the answers

What type of information does the spinothalamic tract transmit?

Pain, temperature, and crude touch and sexual sensations from the opposite side Signup and view all the answers

What is the primary function of the spinomedullary and spinobulbar projections in the pain modulation pathway?

To allow integration of pain and processes of homeostasis and behavior into primitive parts of the brain Signup and view all the answers

What nerve fibers transmit pain via the ascending pathway?

A-delta fibers Signup and view all the answers

What type of neurons make up the majority of the dorsal horn neurons?

Inhibitory interneurons that communicate via GABA or glycine Signup and view all the answers

What is the purpose of projection neurons in the ascending pain pathway?

To transmit pain signals to the brain Signup and view all the answers

What are the two subdivisions of the spinothalamic tract/anterolateral pathway?

Neospinothalamic and Paleospinothalamic Signup and view all the answers

What type of fibers transmit fast pain signals into the dorsal horn via the neospinalthalamic tract?

A-delta fibers Signup and view all the answers

What type of fibers transmit slow pain to the dorsal horn via the paleospinothalamic tract?

C-fibers Signup and view all the answers

What is the pathway for fast pain to the cortex?

A-delta fibers to the dorsal horn, decussate/cross, then ascend to the thalamus, and finally to the primary somatosensory cortex Signup and view all the answers

What feature allows quicker localization of stimulus in the neospinothalamic tract?

Myelination of the A-d nerve fibers Signup and view all the answers

What is the key neurotransmitter for A-delta fibers in the neospinothalamic tract?

Glutamate Signup and view all the answers

Where do first-order/A-delta fibers terminate in the dorsal horn?

Lamina I (marginal zone) Signup and view all the answers

Where do first-order nociceptor (C-fibers) terminate in the dorsal horn?

Lamina II (substantia gelatinosa) Signup and view all the answers

What is the pathway for slow pain to the cortex?

C fibers to the substantia gelatinosa and lamina V, decussate/cross, then ascend primarily to the lower regions of the brain with some in thalamus Signup and view all the answers

Where do slow pain signals terminate in the brain causing sleep impairment?

Arousal centers = thalamus and reticular area Signup and view all the answers

What is the effect of enkephalin on C and Aδ fibers in the dorsal horns?

It causes pre and postsynaptic inhibition Signup and view all the answers

Localization of slow pain is imprecise

True Signup and view all the answers

Which neurotransmitters are involved in slow pain signal transmission?

Glutamate is released instantly and substance P is released slowly Signup and view all the answers

In the descending pain pathway, which brain regions transmit signals to the PAG?

Prefrontal cortex, insula, amygdala, and hypothalamus Signup and view all the answers

What type of pathways are involved in pain modulation by the locus coeruleus in the pons?

Noradrenergic (norepinephrine-releasing) Signup and view all the answers

Where do the majority of the fibers from the PAG synapse, and what neurotransmitter do they secrete?

RVM, serotonin Signup and view all the answers

What is the primary neurotransmitter secreted by the PAG fibers that bypass the RVM and descend to the dorsal horns?

Serotonin Signup and view all the answers

What is the main difference between the serotonergic and noradrenergic descending pain pathways?

Serotonergic pathways involves the RVM while noradrenergic pathways involve the LC. Signup and view all the answers

What is the effect of descending signals on interneurons in the dorsal horn?

Stimulate the release of enkaphalin and other endogenous opioids Signup and view all the answers

What is the Lissauer tract?

A bundle of nerve fibers in the spinal cord that contains ascending spinothalamic pathways Signup and view all the answers

What is the role of the anterior cingulate cortex (ACC) and insular cortex in pain modulation?

Emotional and motivation aspects of pain Signup and view all the answers

Which type of pain fibers transmit all pain from viscera?

C Signup and view all the answers

Why are the parenchyma of the liver and alveoli insensitive to pain?

Because they lack nocioceptors Signup and view all the answers

What are the two pathways that visceral sensations are transmitted?

True visceral pathway - referred through autonomic nerve bundles Signup and view all the answers

What is the difference between A-d and C fibers in temperature transmission?

A-d fibers transmit cold temperatures, while C fibers transmit warm temperatures Signup and view all the answers

What type of nerve fibers transmit pain signals at the extremes of hot and cold?

Aδ and C fibers - transmit temperature and pain Signup and view all the answers

Cold receptors (a-d fibers) are more abundant than warm receptors (C-fibers)

True Signup and view all the answers

Which two sets of nerves innervate visceral organs?

Vagal/spinal and pelvic parasympathetic nerves Signup and view all the answers

What type of nerve fibers are visceral nerves composed of?

Aδ, Aβ, and C fibers Signup and view all the answers

What is the mechanism responsible for two-point discrimination?

Lateral inhibition of adjacent neurons causing decreased sensation at the edge of the field Signup and view all the answers

What is the main reason for an increased ability to distinguish two points of stimulation on different parts of the body?

Increased density of receptor fields Signup and view all the answers

Where do the dorsal column and anterolateral tracts partially join?

Thalamus Signup and view all the answers

What is the difference in decussation in the dorsal-column and anterolateral tracts?

Dorsal-column tracts ascend then cross at the medulla; anterolateral tracts cross at the spinal cord then ascend Signup and view all the answers

What types of information are transmitted via the dorsal column medial leminiscal system?

Vibration and proprioception Signup and view all the answers

What types of information are transmitted via the anterolateral system?

All of the above Signup and view all the answers

Which spinocerebro tract do lateral branch fibers in the dorsal column pathway form?

spinocerebellar tract Signup and view all the answers

What dorsal column fibers play a role in the spinal cord reflex?

Lateral branch fibers Signup and view all the answers

In the dorsal column pathway, what nerve joins the fibers at the level of the brainstem?

Trigeminal nerve Signup and view all the answers

Where do all sensory signals terminate in the brain?

In the cerebral cortex posterior to the central fissure Signup and view all the answers

Which of the following statements is true regarding the cortical processing of sensory information?

Each side of the cortex receives information from the opposite side of the body Signup and view all the answers

At each synaptic stage along the dorsal column pathway, what occurs?

Divergence Signup and view all the answers

What happens as the strength of the stimulus increases in the pain modulation pathway?

More neurons fire and those in the center of the discharge fire more rapidly Signup and view all the answers

What can be expected to happen to ipsilateral pathways in spinal cord injuries?

Ipsilateral dysfunction of dorsal and motor pathways Signup and view all the answers

What can be expected to happen to contralateral pathways in spinal cord injuries?

Contralateral dysfunction in anterolateral pathways Signup and view all the answers

Why do anterolateral pathway signals have less discrete localization?

They are slower than dorsal column system with less ability to convey rapidly changing or repetitive signal Signup and view all the answers

The motor pathway follows the same path as the dorsal column system by crossing at the medulla and then descending down the spinal cord

True Signup and view all the answers

Where do upper motor neurons synapse with lower motor neurons?

In the spinal cord Signup and view all the answers

Where do divergent signals occur in the central nervous system?

Multiple synapses with multiple nuclei and motor output pathways Signup and view all the answers

What is the mechanism by which receptors initially respond rapidly, then progressively respond slower, known as?

Adaptation Signup and view all the answers

Chemoreceptors and pain receptors probably never adapt completely

True Signup and view all the answers

What are the two mechanisms by which mechanoreceptors adapt?

Redistribution of receptor fluid reduces pressure on the receptor Signup and view all the answers

What type of receptors continually transmit status information?

Slowly adapting 'tonic' receptors Signup and view all the answers

What is true about phasic receptors in relation to stimuli and changes in strength?

They adapt quickly to stimuli and changes in strength Signup and view all the answers

Which of the following types of receptors are considered tonic receptors?

All of the above Signup and view all the answers

What happens to the frequency of repetitive receptor action potentials as the strength of the receptor potential increases?

It increases Signup and view all the answers

What is the primary function of the labeled line principle in receptor pathways?

Specificity of nerve fibers only transmitting one modality of sensation Signup and view all the answers

What is the definition of spatial summation?

Increased signal strength spreads to a progressively greater number of nerve fibers Signup and view all the answers

What is temporal summation?

When a nerve fiber has a higher frequency of firing resulting in a stronger signal Signup and view all the answers

What is a neuronal pool in the context of sensory integration?

A functional group of neurons that play a role in sensory integration Signup and view all the answers

What is the difference between the discharge zone and the facilitated zone in a neuronal pool?

The discharge zone is where the neurons are receive the greatest signal and have a greater chance of depolarizing Signup and view all the answers

What type of inhibition is necessary to flex your arm?

Reciprocal Inhibition where the incoming signal generates excitation in biceps and inhibition in triceps Signup and view all the answers

What is the primary purpose of reverberating/oscillatory circuits?

To control rhythmic and repetitive actions e.g. breathing and walking Signup and view all the answers

In a reverberating circuit, what is the pathway of transmission?

Input signal goes to output neuron. Output neuron sends collateral nerve fiber to go back and restimulate itself Signup and view all the answers

How are signal overload and reverberating circuits prevented in the pain modulation pathway?

Inhibitory circuits and synaptic fatigue Signup and view all the answers

Where is 2-point discrimination consciously perceived at?

somatosensory area 1 Signup and view all the answers

What is the main difference between Complex Regional Pain Syndrome (CRPS) 1 and 2?

CRPS 1 develops after a noxious event without nerve injury where CRPS 2 develops after a nerve injury Signup and view all the answers

What is the neurological basis for the development of chronic pain?

Sensitization Signup and view all the answers

In Pacinian corpuscles, what is the characteristic of the receptor potential in response to levels of stimulation?

It changes markedly with low levels of stimulation Signup and view all the answers

Chemicals that excite chemical pain are serotonin, bradykinin, histamine, potassium ions

True Signup and view all the answers

Study Notes

Pain Modulation

Pain signal arrives at the brain from the spinothalamic tract via the ascending pathway
Prefrontal cortex, insula, amygdala, and hypothalamus transmit the signal to the PAG (periaqueductal gray)
PAG transmits signal to the RVM (rostral ventromedial medulla) and Locus ceruleus
RVM transmits signal down spinal cord releasing serotonin to inhibit/excite ascending pain pathways
Locus ceruleus transmits signal down spine releasing NE (norepinephrine) to inhibit pain in the ascending pain pathways

Descending Pain Modulation

Descending signal also stimulates interneurons in dorsal horn to release endogenous opioid, enkaphalin
Enkaphalin inhibits release of substance P from presynaptic neuron and inhibits transmission of pain signal from the postsynaptic neuron

Gate Theory

The faster transmission of the Aβ fibers essentially overrides input from the slower Aδ and C fibers
Indirect activators activate the inflammatory cells to release cytokines to induce primary hyperalgesia
Cytokines are both direct and indirect activators of nociceptor sensitization

Role of CNS in Pain Physiology

Spinal dorsal horn is the relay center for nociception
Superficial dorsal horn (lamina I and II) serves as the main target for C fibers
Lamina V is the site of wide dynamic range neurons, which play a role in perception of pain intensity and modulation of pain signals
Somatosensory cortices (S1 and S2) in the forebrain process where the pain is coming from and how intense it is
Anterior cingulate cortex, insular cortex, prefrontal cortex, and thalamus provide an interpretation of the pain and the emotional response to the pain

Pain Processing

Transduction: heat, cold, mechanical distortion is sensed by receptor and then converted into electrical impulses
Transmission: conduction of electrical impulses through the dorsal horn and thalamus to the higher brain centers
Modulation: inhibitory or excitatory alteration of the pain transmission
Perception: thalamus acts as the relay station for signals traveling to the somatosensory cortex

Fiber Types

C fibers respond to heat and sustained pressure
A fibers:
- Type 1 (A-b) respond to heat, mechanical, and chemical stimulation (polymodal)
- Type 2 (A-d) respond only to heat

Nociceptor Sensitization

Nociceptors are normally at rest
Inflammatory cells release cytokines potentiating nociceptor responses and leading to sensitization
Sensitization leads to transition from acute to chronic pain when inflammatory processes do not resolve
Hyperalgesia: increased pain sensations to painful stimuli
Primary hyperalgesia: occurs at the site of injury and is the result of increased sensitivity to nociceptors at the injury site
Secondary hyperalgesia: manifested at the uninjured skin surrounding the original injury (mechanical stimuli only)
Allodynia: perception of pain from normally non-painful stimuli

Windup

Windup is a type of sensitization where repeated, low frequency stimulation of pain pathways leads to an increased response to pain due to increased excitability of neurons in the spinal cord
Causes: accumulation of glutamate and substance P causing prolonged activation of NMDA receptors and therefore increased excitability of the dorsal horn neurons
Heterosynaptic activity-dependent plasticity: a type of sensitization where after a period of intense stimulus, normally subthreshold stimulus causes activation

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Description

The pain modulation pathway involves the transmission of pain signals from the spinal cord to the brain, and the subsequent modulation of pain through the release of serotonin and other neurotransmitters. The rostral ventromedial medulla and periaqueductal gray play key roles in this process.