Sensory: pain and temp Flashcards
Nociception (sensing pain) can be subdivided into thermosensation, chemosensation and mechanosensation. What are the molecular differences? Give some examples for ion channels belonging to each of the three categories. Explain their membrane topology, channel subunit composition, ion selectivity and gating mechanism.
Thermosensation: gated temperature changes, TRPV1 (sensing capsaicin and > 42 C) - micromovements in any direction
Chemosensation: gated by a chemical ligand TRPM8 (sensing methol), GPCR
Mechanosensation: mechanically gated by either forces from lipids, or forces from filaments: SWELL1 (osmoregulation in vertebrates)
What structures are responsible for sensing pain and temperature?
Free nerve endings
Are the nocireceptors and thermonreceptors in the free nerve endings in the skin low treshold or high treshold receptors?
High treshold
Describe the general route in the PNS for afferent noci-, mechano and proprioceptors.
The primary afferent neuron go through the dorsal root ganglion (cell body) –> dorsal horn (Lissauer’s tract) innervating secondary afferent CNS neurons –> CNS neurons go through the spino-thalamic tract –> spine –> thalamus
What types of fibers are involved in nociception?
A-delta: thin myelin sheath neurons
C: thin, slow conducting fibers (longer lasting pain like headache), unmyelinated
What NT are the pain fibers using?
Glutamate + neuropeptides to amplify the signal
Where are capsaicin binding?
Intracellularly
What kinds of inputs does the 1st layer in the dorsal horn receive?
Sharp pain, burning pain, warmth, cold, itch and sensual touch
What kinds of inputs does the 5th layer in the dorsal horn receive?
Receive input from both touch and pain, wide dynamic range neurons
What pathway does the pain and temp sensing secondary fibers take in the spinal cord?
The anterolateral root
What pathway does the mechanosensory sensing secondary fibers take in the spinal cord?
The dorsal column root
Which side of the body will a lesion in the left side of the spinalcord effect on pain/temp and on mechanoception?
Pain/temp: the opposite side
Mechano: same side
Describe the central pathway of visceral pain.
–> dorsal root ganglion –> gracile nucleus in the medulla –> medial lemniscus pathway to the thalamus –> insular cortex
Describe the sensory-discriminative (1st pain) route.
Anterolateral system –> ventral posterior lateral nucleus in the thalamus –> somatosensory cortex (SI, SII)
Describe the affective-motivational (2nd pain) pathway.
Example: anterolateral system –> parabrachial nucleus –> hypothalamus –> amygdala –> anterior cingulate cortex and insula
What are the affective-motivational pathway associated with?
General well-being, e.g., anxiety
Describe the descending pain control pathway.
“top-down” regulation (simplification) –> release of endorphines
What are some of the substances triggering the pain sensation?
ATP, histamine, 5-HT, H+, prostaglandin
What types of drugs can be used as a treatment for pain?
Opioids and NSAIDS (ibuprofen/paracetamol)
Where does NSAIDS work?
On the mediator release (inhibits)
Where does opioids work?
On the neuropeptide release (inhibits), excitation of neurotransmission (inhibits) or the descending inhibitory pathways (stim)
What causes neuropathic pain, and what are the symptoms?
By damage or injury to the nerves
Abnormal pain from normally non-painful stimuli and spontaneous pain
What can induce neuropathic pain?
Diabetes and chemotherapy, etc
How does antidepressants work?
NET-reuptake inhibitors –> increase the NT pool in the synaptic cleft
How does antiepileptica work?
Inhibit T-type Ca2+ channels or VGNaC, and inhibits release of various NTs (unknown action)
How does NMDA-R antagonists work, and what can it be used for?
Inhibits central sensitization and wind-up effect
Neuropathic pain and trigenemius pain
How does adrenergic agonists work?
Activates presynaptic alpha_2-R –> decrease activation of Ca2+ channels
What does PICK1 do?
Tune synaptic transmission by modulating AMPA-R phosphorylation and trafficking
What model can be used to study neuropathic pain?
Spared nerve injury model
Describe the primary cortical pain matrix?
Thalamus –> S1 –> S2 –> parietal operculum
Describe the secondary cortical pain matrix?
(thalamus) –> INS/ACC –> amygdala/hippocampus
Describe the third cortical pain matrix?
PCC <–> MCC –> (ACC) –> PFC
How are chronic pain different from “normal pain”/non chronic pain?
Beta-fibers become pain conducting
