Grover - Peripheral Mechanisms of Pain

Question 1

What division of the CNS mediates pain?

Answer 1

Somatosensory

Question 2

WHat type of endings are pain receptors, and what activates them?

Answer 2

Free nerve endings

Activated by mechanical, thrmal, and/or chemical stimulation

Question 3

What type of transduction mechanisms do pain receptors share w/other somatosensory receptors?

Answer 3

Stretch-gated ion channels

Temperature sensitive (TRP) channels

Chemical Signals (seotonin, histamine, bradykinin, potassium, acid)

Question 4

Two Classifications or Nociceptors

A(delta)

C

Answer 4

A(delta):

Small diameter

Myelinated

Activation: Mechanosensitive, Mechanothermal

C:

Small diameter

Unmyelinated

Polymodal activation

Question 5

What chemicals directly activate noceiceptors?

Answer 5

Serotonin (5-HT)

Bradykinin

Potassium (K+)

Histamine

Question 6

What chemicals sensitive nociceptors? (decrease threshold)

Answer 6

Arachidonic Acid Metabolites (prostaglandins, leikotrienes)

Substance P / CGRP

Question 7

What is unique about serotonin w/nociceptors?

Answer 7

It can activate and sensitize

Question 8

What rule do 5-HT3 receptors break?

Answer 8

Monoamine receptors are usually metabotropic, but it is ionotropic

Question 9

What chemicals are released in response to injury through the axon reflex?

Answer 9

Substance P / CGRP

Histamine

Question 10

What is the conduction direction of action potentials triggered by injury to nerve endings?

Answer 10

Ortodromic to dorsal horn of spinal cord

Antidromic to other endings of same receptor

Question 11

What neurotransmitter is released by nociceptors?

What is often co-released?

Answer 11

Glutamate

Substance P or CGRP

Question 12

Primary Hyperalgesia

Answer 12

Peripheral mechanism to modulate pain, area may become hyper sensitive to pain

In tissue surrounding site of injury

Caused by peripheral reslease of chemical activators and sensitizers

Axon reflex release Substance P and CGRP

Question 13

Analgesia vs Hyperalgesia

Answer 13

Hyperalgesia = lower threshold for pain (increased sensitivity), ex: Sunburn

Analgesia = increased threshold for pain (decreased sensitivity), ex: local Anesthesia

Question 14

Secondary Hyperalgesia

Answer 14

Centrally mediated

Spinal level and brain

Enhances pain transmission through central pathways through multiple mechanisms

Question 15

Allodynia

vs

Spontaneous Pain

Answer 15

Painful response to non-noxious stimulatione

Ex. Wearing a shirt with a sunburn

Sensation of pain in absence of any apparent stimulation

Question 16

Acute vs Chronic Pain

Answer 16

Acute = Short

Chronic = 3-6 months

Question 17

Neuropathic Pain

Answer 17

Caused by damage to dysfunction in PNS or CNS

Question 18

Ectopic Firing

Answer 18

Action potential generation at abnormal location on neuron (out of normal place)

Contributes to spontaneous pain

Question 19

Neuroma

Answer 19

Tangle of axon sprouts and proliferating Schwann cells

Can generate ectopic action potentials

One reason for spontaneous pain, triggered by abnormal sodium channel expression

Question 20

What type of channels are upregulated following nerve injury?

Answer 20

TRP Channels

Contributes to Thermal Hyperalgesia

(skin is more sensitive to temperature when you’re sunburnt)

Question 21

Cyclo-oxygenase Inhibition and Analgesia

Answer 21

Cyclo-oxygenase Inhibitors (aspirin and other NSAIDs) inhibity formation of prostaglandins in injured tissue

Reduces production of pain sensitizer