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What are the three main types of stimuli that can elicit acute pain?
Mechanical, thermal, and chemical stimuli.
How do mechanical, thermal, and chemical stimuli activate nociceptors?
Mechanical stimuli open mechanically gated ion channels; thermal stimuli open thermally gated ion channels; chemical stimuli activate ligand-gated ion channels or G-protein coupled receptors.
List some common transducers involved in nociception.
TRP channels, ASICs, P2X receptors, PIEZO channels.
What is a receptive field?
The area of sensory surface (e.g., skin) that elicits a neuronal response in a single sensory neuron.
Define a dermatome.
A region of skin innervated by a single spinal root.
How many pairs of spinal nerves are there?
31 pairs of spinal nerves.
How many vertebral bones are there?
30 vertebral bones.
How many dorsal root ganglia (DRG) are there?
31 dorsal root ganglia.
Why are there only 30 dermatomes?
Because there is no C1 dermatome.
What is another anomaly in the dermatome map?
There is no spinal dermatome on the face; it is supplied by the trigeminal nerve.
Where are the dorsal root ganglia located?
In the intervertebral foramen between adjacent vertebrae.
Where is the trigeminal ganglion located?
In Meckel’s cave within the dura mater.
Can nociceptors respond to more than one type of stimulus?
Yes, polymodal nociceptors can respond to mechanical, thermal, and chemical stimuli.
Which DRG innervates the big toe?
L4 dorsal root ganglion.
What are the three branches of the trigeminal nerve that form the facial dermatome?
Ophthalmic (V1), Maxillary (V2), and Mandibular (V3) branches.
What is congenital insensitivity to pain?
A rare genetic disorder where individuals cannot feel physical pain.
What is the function of the PRDM12 gene?
It encodes a transcriptional regulator essential for the development of nociceptors.
How does a PRDM12 mutation cause congenital analgesia?
Individuals lack functional nociceptors due to disrupted developmental specification.
How does a SCN9A mutation lead to congenital analgesia?
SCN9A encodes the NaV1.7 sodium channel required for action potential conduction in nociceptors; its loss prevents signal transmission to the CNS.
Which laminae of the spinal cord dorsal horn receive sensory afferent inputs?
Laminae I, II, and V.
Through which structure do NS and WDR axons cross the spinal cord midline?
The anterior white spinal commissure.
In which white matter column do pain and temperature fibers ascend?
The anterolateral white column.
Which receptor is prominent in lamina I neurons receiving peptidergic input?
NK1 receptors (bind substance P).
What is the termination site and function of the spinothalamic tract?
Ventrobasal thalamus; conveys crude sensation and relays to the cortex.
What is the termination site and function of the spinoreticular tract?
Brainstem reticular formation and raphe nuclei; involved in pain modulation and autonomic responses.
What is the termination site and function of the spinomesencephalic/spinotectal tract?
Midbrain structures such as the colliculi and periaqueductal gray; involved in pain modulation and orienting to pain.
What is the difference between the neospinothalamic and paleospinothalamic tracts?
The neospinothalamic tract is newer, has fewer synapses, and conveys fast, discriminative pain; the paleospinothalamic tract is older, more multisynaptic, and conveys slow, crude pain.
In Brown-Sequard syndrome, why is pain and temperature loss contralateral but proprioception loss ipsilateral?
Pain/temperature fibers cross in the spinal cord (anterolateral system), while proprioceptive fibers cross in the medulla (dorsal column system).
Why is motor control affected ipsilaterally in Brown-Sequard syndrome?
Because corticospinal tracts cross in the medullary pyramids, not the spinal cord.
What is the pain matrix?
A network of brain regions collectively responsible for processing the sensory and affective dimensions of pain.
Which thalamic nuclei are involved in the lateral and medial pain systems?
VPL and VPM nuclei (lateral pain system), and mediodorsal (MD) nucleus (medial pain system).
What input does the VPL thalamic nucleus receive and where does it project?
Receives neospinothalamic input and projects to Brodmann areas 3, 1, and 2 in the postcentral gyrus.
What is different about the VPM compared to the VPL?
VPM receives trigeminothalamic input conveying facial sensory information, including taste from the solitary tract.
What structure lies between the temporal and parietal lobes when separated?
The insular cortex.
Which cortical layer receives thalamic sensory inputs?
Layer 4 of the primary somatosensory cortex.
What is the role of the secondary somatosensory cortex (SII)?
Integrates sensory information from both body halves, attention, learning, and sensorimotor integration.
Which regions form the medial pain system?
Insula, anterior cingulate cortex, and limbic structures.
How do chronic pain states alter neural processing?
Chronic pain changes gene expression and neuronal phenotype, creating unique neurochemical signatures that complicate treatment.
What is the main descending pain control system called?
The endogenous analgesia system.
Which brainstem nuclei are key components of the descending analgesia pathway?
Periaqueductal gray (PAG), rostral ventromedial medulla (RVM/raphe magnus), and locus coeruleus.
What are the neurotransmitters used by PAG, RVMM, and LC?
PAG: opioids; RVMM: serotonin (5-HT); LC: noradrenaline (NA).
What are the functions of the periaqueductal gray besides analgesia?
Autonomic regulation, bladder control, vocalization, respiration, and emotional responses.
Name five forebrain regions that influence descending pain control.
Prefrontal cortex, anterior cingulate cortex, insula, amygdala, and hypothalamus.
What is the thermal grill illusion?
A sensory illusion where interlaced warm and cool stimuli produce a burning pain sensation without tissue damage.
What does the thermal grill illusion suggest about pain mechanisms?
It indicates that simultaneous activation of warm and cool pathways can aberrantly activate nociceptive circuits through disinhibition.
What is central inhibition in the context of temperature and pain?
Cool-sensitive pathways inhibit nociceptive pathways to prevent pain during normal temperature sensations.
What real-life example supports central inhibition?
Applying a cool cloth to an injury reduces pain by engaging inhibitory cooling pathways.
What is central disinhibition in the thermal grill illusion?
Simultaneous warm and cool stimulation suppresses the inhibitory cool pathway, disinhibiting nociceptive neurons and creating pain.
Which cortical areas are involved in processing the thermal grill illusion?
Insular and cingulate cortices.
What role does the insula play in pain processing?
Integrates sensory, affective, and cognitive components of pain and other sensations.