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Questions and Answers
What is the primary function of the rostral ventromedial medulla (RVM)?
What is the primary function of the rostral ventromedial medulla (RVM)?
Which of the following brain regions transmits signals to the periaqueductal gray (PAG)?
Which of the following brain regions transmits signals to the periaqueductal gray (PAG)?
What is the primary mechanism by which the locus ceruleus modulates pain?
What is the primary mechanism by which the locus ceruleus modulates pain?
What is the role of enkaphalin in pain modulation?
What is the role of enkaphalin in pain modulation?
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According to the Gate Theory, what is the primary mechanism by which pain is modulated?
According to the Gate Theory, what is the primary mechanism by which pain is modulated?
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What is the primary source of the brain's norepinephrine which plays a role in inhibiting substance P?
What is the primary source of the brain's norepinephrine which plays a role in inhibiting substance P?
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Which of the following types of fibers respond to heat, mechanical, and chemical stimulation (polymodal) and travel via the dorsal medial leminiscal tract?
Which of the following types of fibers respond to heat, mechanical, and chemical stimulation (polymodal) and travel via the dorsal medial leminiscal tract?
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What is the result of nociceptor sensitization?
What is the result of nociceptor sensitization?
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What is the site of conscious pain?
What is the site of conscious pain?
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What is the result of heterosynaptic activity-dependent plasticity?
What is the result of heterosynaptic activity-dependent plasticity?
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What is the main difference between hyperalgesia and heterosynaptic activity-dependent plasticity?
What is the main difference between hyperalgesia and heterosynaptic activity-dependent plasticity?
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What is the main difference between direct activators and other neurotransmitters?
What is the main difference between direct activators and other neurotransmitters?
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What is the result of secondary hyperalgesia?
What is the result of secondary hyperalgesia?
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What is the primary function of the superficial dorsal horn (lamina I and II)?
What is the primary function of the superficial dorsal horn (lamina I and II)?
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Which of the following brain regions is responsible for processing the location and intensity of pain?
Which of the following brain regions is responsible for processing the location and intensity of pain?
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What is the role of wide dynamic range neurons located in lamina V?
What is the role of wide dynamic range neurons located in lamina V?
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What is the function of cytokines in nociceptor sensitization?
What is the function of cytokines in nociceptor sensitization?
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What is the result of primary hyperalgesia, which is characterized by increased nociceptors' sensitivity at the injury site?
What is the result of primary hyperalgesia, which is characterized by increased nociceptors' sensitivity at the injury site?
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What is allodynia?
What is allodynia?
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What happens when inflammatory processes do not resolve in the pain pathway?
What happens when inflammatory processes do not resolve in the pain pathway?
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What is the main difference between windup/secondary hyperalgesia and primary hyperalgesia?
What is the main difference between windup/secondary hyperalgesia and primary hyperalgesia?
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What causes windup?
What causes windup?
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What are common features of neuropathic pain?
What are common features of neuropathic pain?
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What is the correct description of lamina II and III?
What is the correct description of lamina II and III?
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What type of stimuli do C fibers respond to?
What type of stimuli do C fibers respond to?
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What is the main difference between convergent and divergent neurons in the pain modulation pathway?
What is the main difference between convergent and divergent neurons in the pain modulation pathway?
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What is the role of descending monoaminergic (serotonin and norepinephrine) neurons in pain modulation?
What is the role of descending monoaminergic (serotonin and norepinephrine) neurons in pain modulation?
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What type of information does the spinothalamic tract transmit?
What type of information does the spinothalamic tract transmit?
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What is the primary function of the spinomedullary and spinobulbar projections in the pain modulation pathway?
What is the primary function of the spinomedullary and spinobulbar projections in the pain modulation pathway?
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What nerve fibers transmit pain via the ascending pathway?
What nerve fibers transmit pain via the ascending pathway?
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What type of neurons make up the majority of the dorsal horn neurons?
What type of neurons make up the majority of the dorsal horn neurons?
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What is the purpose of projection neurons in the ascending pain pathway?
What is the purpose of projection neurons in the ascending pain pathway?
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What are the two subdivisions of the spinothalamic tract/anterolateral pathway?
What are the two subdivisions of the spinothalamic tract/anterolateral pathway?
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What type of fibers transmit fast pain signals into the dorsal horn via the neospinalthalamic tract?
What type of fibers transmit fast pain signals into the dorsal horn via the neospinalthalamic tract?
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What type of fibers transmit slow pain to the dorsal horn via the paleospinothalamic tract?
What type of fibers transmit slow pain to the dorsal horn via the paleospinothalamic tract?
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What is the pathway for fast pain to the cortex?
What is the pathway for fast pain to the cortex?
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What feature allows quicker localization of stimulus in the neospinothalamic tract?
What feature allows quicker localization of stimulus in the neospinothalamic tract?
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What is the key neurotransmitter for A-delta fibers in the neospinothalamic tract?
What is the key neurotransmitter for A-delta fibers in the neospinothalamic tract?
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Where do first-order/A-delta fibers terminate in the dorsal horn?
Where do first-order/A-delta fibers terminate in the dorsal horn?
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Where do first-order nociceptor (C-fibers) terminate in the dorsal horn?
Where do first-order nociceptor (C-fibers) terminate in the dorsal horn?
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What is the pathway for slow pain to the cortex?
What is the pathway for slow pain to the cortex?
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Where do slow pain signals terminate in the brain causing sleep impairment?
Where do slow pain signals terminate in the brain causing sleep impairment?
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What is the effect of enkephalin on C and Aδ fibers in the dorsal horns?
What is the effect of enkephalin on C and Aδ fibers in the dorsal horns?
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Localization of slow pain is imprecise
Localization of slow pain is imprecise
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Which neurotransmitters are involved in slow pain signal transmission?
Which neurotransmitters are involved in slow pain signal transmission?
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In the descending pain pathway, which brain regions transmit signals to the PAG?
In the descending pain pathway, which brain regions transmit signals to the PAG?
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What type of pathways are involved in pain modulation by the locus coeruleus in the pons?
What type of pathways are involved in pain modulation by the locus coeruleus in the pons?
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Where do the majority of the fibers from the PAG synapse, and what neurotransmitter do they secrete?
Where do the majority of the fibers from the PAG synapse, and what neurotransmitter do they secrete?
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What is the primary neurotransmitter secreted by the PAG fibers that bypass the RVM and descend to the dorsal horns?
What is the primary neurotransmitter secreted by the PAG fibers that bypass the RVM and descend to the dorsal horns?
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What is the main difference between the serotonergic and noradrenergic descending pain pathways?
What is the main difference between the serotonergic and noradrenergic descending pain pathways?
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What is the effect of descending signals on interneurons in the dorsal horn?
What is the effect of descending signals on interneurons in the dorsal horn?
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What is the Lissauer tract?
What is the Lissauer tract?
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What is the role of the anterior cingulate cortex (ACC) and insular cortex in pain modulation?
What is the role of the anterior cingulate cortex (ACC) and insular cortex in pain modulation?
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Which type of pain fibers transmit all pain from viscera?
Which type of pain fibers transmit all pain from viscera?
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Why are the parenchyma of the liver and alveoli insensitive to pain?
Why are the parenchyma of the liver and alveoli insensitive to pain?
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What are the two pathways that visceral sensations are transmitted?
What are the two pathways that visceral sensations are transmitted?
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What is the difference between A-d and C fibers in temperature transmission?
What is the difference between A-d and C fibers in temperature transmission?
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What type of nerve fibers transmit pain signals at the extremes of hot and cold?
What type of nerve fibers transmit pain signals at the extremes of hot and cold?
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Cold receptors (a-d fibers) are more abundant than warm receptors (C-fibers)
Cold receptors (a-d fibers) are more abundant than warm receptors (C-fibers)
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Which two sets of nerves innervate visceral organs?
Which two sets of nerves innervate visceral organs?
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What type of nerve fibers are visceral nerves composed of?
What type of nerve fibers are visceral nerves composed of?
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What is the mechanism responsible for two-point discrimination?
What is the mechanism responsible for two-point discrimination?
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What is the main reason for an increased ability to distinguish two points of stimulation on different parts of the body?
What is the main reason for an increased ability to distinguish two points of stimulation on different parts of the body?
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Where do the dorsal column and anterolateral tracts partially join?
Where do the dorsal column and anterolateral tracts partially join?
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What is the difference in decussation in the dorsal-column and anterolateral tracts?
What is the difference in decussation in the dorsal-column and anterolateral tracts?
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What types of information are transmitted via the dorsal column medial leminiscal system?
What types of information are transmitted via the dorsal column medial leminiscal system?
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What types of information are transmitted via the anterolateral system?
What types of information are transmitted via the anterolateral system?
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Which spinocerebro tract do lateral branch fibers in the dorsal column pathway form?
Which spinocerebro tract do lateral branch fibers in the dorsal column pathway form?
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What dorsal column fibers play a role in the spinal cord reflex?
What dorsal column fibers play a role in the spinal cord reflex?
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In the dorsal column pathway, what nerve joins the fibers at the level of the brainstem?
In the dorsal column pathway, what nerve joins the fibers at the level of the brainstem?
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Where do all sensory signals terminate in the brain?
Where do all sensory signals terminate in the brain?
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Which of the following statements is true regarding the cortical processing of sensory information?
Which of the following statements is true regarding the cortical processing of sensory information?
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At each synaptic stage along the dorsal column pathway, what occurs?
At each synaptic stage along the dorsal column pathway, what occurs?
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What happens as the strength of the stimulus increases in the pain modulation pathway?
What happens as the strength of the stimulus increases in the pain modulation pathway?
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What can be expected to happen to ipsilateral pathways in spinal cord injuries?
What can be expected to happen to ipsilateral pathways in spinal cord injuries?
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What can be expected to happen to contralateral pathways in spinal cord injuries?
What can be expected to happen to contralateral pathways in spinal cord injuries?
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Why do anterolateral pathway signals have less discrete localization?
Why do anterolateral pathway signals have less discrete localization?
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The motor pathway follows the same path as the dorsal column system by crossing at the medulla and then descending down the spinal cord
The motor pathway follows the same path as the dorsal column system by crossing at the medulla and then descending down the spinal cord
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Where do upper motor neurons synapse with lower motor neurons?
Where do upper motor neurons synapse with lower motor neurons?
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Where do divergent signals occur in the central nervous system?
Where do divergent signals occur in the central nervous system?
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What is the mechanism by which receptors initially respond rapidly, then progressively respond slower, known as?
What is the mechanism by which receptors initially respond rapidly, then progressively respond slower, known as?
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Chemoreceptors and pain receptors probably never adapt completely
Chemoreceptors and pain receptors probably never adapt completely
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What are the two mechanisms by which mechanoreceptors adapt?
What are the two mechanisms by which mechanoreceptors adapt?
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What type of receptors continually transmit status information?
What type of receptors continually transmit status information?
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What is true about phasic receptors in relation to stimuli and changes in strength?
What is true about phasic receptors in relation to stimuli and changes in strength?
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Which of the following types of receptors are considered tonic receptors?
Which of the following types of receptors are considered tonic receptors?
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What happens to the frequency of repetitive receptor action potentials as the strength of the receptor potential increases?
What happens to the frequency of repetitive receptor action potentials as the strength of the receptor potential increases?
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What is the primary function of the labeled line principle in receptor pathways?
What is the primary function of the labeled line principle in receptor pathways?
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What is the definition of spatial summation?
What is the definition of spatial summation?
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What is temporal summation?
What is temporal summation?
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What is a neuronal pool in the context of sensory integration?
What is a neuronal pool in the context of sensory integration?
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What is the difference between the discharge zone and the facilitated zone in a neuronal pool?
What is the difference between the discharge zone and the facilitated zone in a neuronal pool?
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What type of inhibition is necessary to flex your arm?
What type of inhibition is necessary to flex your arm?
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What is the primary purpose of reverberating/oscillatory circuits?
What is the primary purpose of reverberating/oscillatory circuits?
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In a reverberating circuit, what is the pathway of transmission?
In a reverberating circuit, what is the pathway of transmission?
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How are signal overload and reverberating circuits prevented in the pain modulation pathway?
How are signal overload and reverberating circuits prevented in the pain modulation pathway?
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Where is 2-point discrimination consciously perceived at?
Where is 2-point discrimination consciously perceived at?
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What is the main difference between Complex Regional Pain Syndrome (CRPS) 1 and 2?
What is the main difference between Complex Regional Pain Syndrome (CRPS) 1 and 2?
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What is the neurological basis for the development of chronic pain?
What is the neurological basis for the development of chronic pain?
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In Pacinian corpuscles, what is the characteristic of the receptor potential in response to levels of stimulation?
In Pacinian corpuscles, what is the characteristic of the receptor potential in response to levels of stimulation?
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Chemicals that excite chemical pain are serotonin, bradykinin, histamine, potassium ions
Chemicals that excite chemical pain are serotonin, bradykinin, histamine, potassium ions
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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.