Somatosensation Part 2 Pain

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SomatosensationPart 2Pain

• Lecture 15

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Pain

• Pain perception
• subjective response...
• to a noxious stimulus
• Sensation nociception
• Nociceptors
• primarily free nerve endings

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Function of Pain

• Is it adaptive?
• Signals potential tissue damage
• withdraw from stimulus
• Attend to injury

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Qualities of Pain

• Sharp pain
• acute
• brief, localized skin pain
• produces immediate reaction
• Dull pain
• chronic
• also sweating, palpitations, etc.

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Qualities of Pain

• Referred pain
• originates in internal organ
• e.g., angina
• perceived in other body areas
• Double pain
• rapid sharp, then persistent dull
• Others
• pricking, burning, itching

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Acute vs. Chronic Pain

• Acute ---gt withdrawal reflex
• good pain
• Chronic ---gt during healing
• Neuropathy continued pain after healing
• bad pain
• allodynia, hyperalgesia

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Acute vs. Chronic Pain

• Toxin for substance P receptors
• killed neurons in superficial layer
• eliminated neuropathic pain
• Neurons in lower layers unaffected
• acute pain still functional
• Acute chronic pain different neurons
• Effective treatment for neuropathic

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Pain Stimulus Thresholds

• Stimulus
• mechanical, thermal, chemical stimuli
• Thresholds
• many factors, difficult to determine
• e.g., qualities, inflammation, swelling,
  distribution
• sex threshold during ovulation

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Pain Subjective Factors

• Pain is perception
• more than nociception
• Cognitive emotional factors
• expectation, attention, motivation
• placebo
• meditation
• acupuncture
• stress-induced analgesia
• learned helplessness, sports

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Hyperalgesia

• Following tissue damage
• Nociceptors are sensitized
• light touch can be painful
• adaptive rest injured part
• inflammatory response
• Histamine, Substance P, prostaglandins, etc.

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Pain Pathways

• Anterolateral columns
• pain temperature
• spinolthalamic tract
• spinoreticular tract
• spinomesencephalic tract
• analgesia

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Pain Pathways

• Project to thalamus
• VPL ventroposterior lateral nucleus
• Intralaminar nuclei
• also cortical input
• Primary somatosensory cortex (S1)

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Spinothalamic Tract

• Sensory neuron
• Ad C fibers
• NTs are coreleased
• Glutamate ---gt fast transmission
• Substance P ---gt slow transmission
• projects into gray matter
• 2d order neuron crosses midline
• at spinal cord

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Pain
S1
Thalamus - VPL intralaminar
Spinoreticular Tract
Spinothalamic Tract
Reticular Formation
DRG
R
Spinal Cord
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Analgesia

• Not always adaptive to attend to injury
• fighting, fleeing, mating
• Temporarily decreases...
• nociception
• subjective experience
• Endorphins
• stress-induced analgesia
• acupuncture
• blocked by naloxone

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DescendingAnalgesiaCircuit
PAG
Spino- mesencephalic tract
R
Spinal Cord
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Analgesia in Spinal Cord

• Serotonin neuron mediates
• 5-HT directly inhibits
• activates enkephalin neuron
• opioid
• activates GABA neuron

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Analgesia in Spinal Cord
Presynaptic inhibition
Postsynaptic inhibition
Sub P Glu
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Analgesia in Spinal Cord
Postsynaptic inhibition
Substance P
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Melzack-Wall Gate Theory of Pain

• Why it feels better to rub an injury
• Modulation of pain signals
• by touch pathways
• Gate neuron in spinal cord
• Substantia Gelatinosa
• inhibited by C fibers (pain)
• activated by Ab fibers (touch)
• pain signals in projection neurons

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Melzack-Wall Gate Theory of Pain
Spinothalamic Tract
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Nonopioid Analgesia

• Naloxone bocks opioid-mediated analgesia
• Intermittent shock ---gt no analgesia
• short, continued shock ---gt analgesia
• Suggests nonopioid analgesic systems

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Nonopioid Analgesia

• NMDA (N-methyl-D-aspartate)
• Glutamate receptor
• MK-801 - NMDA antagonist
• MK-801 Naloxone
• blocked analgesia in male rats
• attenuated analgesia in female rats

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Nonopioid Analgesia

• Estrogen-modulated analgesia
• Ovariectomized female rats
• nonopioid analgesia
• estrogen or progesterone ---gt analgesia

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Nonopioid Analgesia

• Potential new analgesic drug
• opiates have undesirable side effects
• Cholinergic-mediated analgesia
• ABT-594 cholinergic agonist
• Comparable to opiate analgesia

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Nonopioid Analgesia

• Developed from frog skin toxin
• epibetadine
• too toxic for humans
• found ACh agonist with similar structure
• Altered ---gt ABT-594

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Temperature

• Thermal sensations
• regulation of body temperature
• changes in skin temperature
• Mainly free nerve endings
• but other receptors also
• cold receptors near surface
• heat receptors at deeper levels