2017-11-02 11:11:42

Prelude I (5:56)

Prelude II (4:56)

Today's Topics

Size/speed trade-off

From skin to brain

  • Cutaneous receptors
  • Dorsal root ganglion
  • Ventral posterior lateral thalamus
  • Primary somatosensory cortex (S1)
    • Parietal lobe

Dermatomes

Dermatomes

Functional segregation

Functional segregation

  • Dorsal column/medial leminiscal pathway
    • Touch, proprioception
  • Spinothalamic tract
    • Pain, temperature

Somatatopic maps

Non-uniform mapping of skin surface

Non-uniform mapping of skin surface

Columnar organization/functional segregation

Phantom Limbs

What/where

  • Perceiving Where
    • Somatotopic maps – where on skin
    • Kinesthesia – configuration of limbs
  • Perceiving What
    • Patterns of smoothness, roughness, shape, temperature

Somatosensation in other animals

The neuroscience of pain

  • Nociceptors (Latin nocere to harm or hurt) detect harmful or potentially harmful stimuli of varied types:
    • chemical
    • mechanical
    • thermal

Nociception

  • External
    • Skin, cornea (eye), mucosa
  • Internal
    • Muscles, joints, bladder, gut

Interoception

  • Receptors for
    • metabolism (acidic pH, hypoxia, …)
    • cell rupture (ATP and glutamate)
    • cutaneous parasite penetration (histamine)
    • mast cell (white blood cell) activation (serotonin, bradykinin, …)
    • immune and hormonal activity (cytokines and somatostatin)

Fast (\(A\delta\)) and slow (\(C\)) transmission to CNS

Thermal grill illusion

'Cross-talk' between nociceptor channels

Projection to brain via anterolateral system

Key CNS nodes in network

  • Periaqueductal grey (PAG)
  • Insular cortex (insula)
  • Hypothalamus
  • Amygdala

Key CNS nodes in network

  • Thalamus
    • Ventroposterior lateral nucleus
    • Ventroposterior medial nucleus
    • Ventromedial nucleus

Pain in the brain

Pain in the brain

"…we used machine-learning analyses to identify a pattern of fMRI activity across brain regions — a neurologic signature — that was associated with heat-induced pain. The pattern included the thalamus, the posterior and anterior insulae, the secondary somatosensory cortex, the anterior cingulate cortex, the periaqueductal gray matter, and other areas…"

(Wager et al. 2013)

Pain relief

  • Prostaglandins
    • hormone-like effects, but released in many places
    • trigger vasodilation and inflammation

Pain relief

  • Paracetymol (acetaminophen)
    • Mechanism not fully understood
    • inhibits synthesis of prostaglandins via cyclooxygenase (COX) enzyme
    • may modulate endocannabinoid system
  • Nonsteroidal anti-inflamatory drugs (NSAIDs): aspirin, ibuprofen
    • Also inhibit prostaglandins via COX

Pain relief

  • Opioids
    • Activate endogenous opioid systems
    • multiple receptor types (\(\delta\), \(\kappa\), \(\mu\),…)
    • peripheral sensory neurons, amygdala, hypothalamus, PAG, spinal cord, cortex, medulla, pons,…
    • brainstem opioid neurons provide descending inhibition of nociceptors

Pain relief

Pain relief

  • Why rubbing can help

Gate control theory (Melzack and Wall 1965)

Gate control theory (Melzack and Wall 1965)

Psychological and physical dimensions

Main points

  • Somatosensation
    • Exteroception via
      • Cutaneous receptors + proprioception
    • Interoception via
      • Widely distributed receptors
      • Specific and non-specific

Main points

  • Pain
    • Multiple receptor channels
    • Highly interconnected CNS network
    • Multiple targets for modulation

Next time…

  • Action

References

Borbiro, Istvan, Doreen Badheka, and Tibor Rohacs. 2015. “Activation of Trpv1 Channels Inhibits Mechanosensitive Piezo Channel Activity by Depleting Membrane Phosphoinositides.” Sci. Signal. 8 (363): ra15. doi:10.1126/scisignal.2005667.

Craig, A D. 2002. “How Do You Feel? Interoception: The Sense of the Physiological Condition of the Body.” Nat. Rev. Neurosci. 3 (8): 655–66. doi:10.1038/nrn894.

Melzack, R, and P D Wall. 1965. “Pain Mechanisms: A New Theory.” Science 150 (3699): 971–79. doi:10.1126/science.150.3699.971.

Papini, Mauricio R, Perry N Fuchs, and Carmen Torres. 2015. “Behavioral Neuroscience of Psychological Pain.” Neurosci. Biobehav. Rev. 48 (January): 53–69. doi:10.1016/j.neubiorev.2014.11.012.

Wager, Tor D, Lauren Y Atlas, Martin A Lindquist, Mathieu Roy, Choong-Wan Woo, and Ethan Kross. 2013. “An fMRI-based Neurologic Signature of Physical Pain.” N. Engl. J. Med. 368 (15): 1388–97. doi:10.1056/NEJMoa1204471.