Temperature and Pain

Question 1

Where does pain and temperature information first enter the CNS and how does it get to the brain?

Answer 1

Pain and temperature information travel through the DRG into the dorsal horn of the spinal column. The neuron synapses in the dorsal horn and the secondary neuron crosses the anterior white commisure to ascend the spinothalamic tract. Some axons will subsequently synapse in the thalamus and be routed to the cerebral cortex while others will enter the spinoreticular or spinomesencephalic tract.

Question 2

What types of sensory information ascend the anterolateral or spinothalamic tract, and what type of neurons does this information originate in?

Answer 2

Pain and temperature info ascends the AL/ST tract. This info originates in Ad and C neurons (the slowest ones).

Question 3

What kind of receptors detect cool temperatures and what effect does cool temps have on them?

Answer 3

Cool receptors are Ad, and cool temps increase their firing rates.

Question 4

What kind of receptors detect warm temperatures and what effect does warm temps have on them?

Answer 4

Warm receptors are C, and warm temps increase their firing rates.

Question 5

What kind of receptors detect uncomfortably cold temperatures?

Answer 5

Severe Cold receptors are C neurons.

Question 6

What kind of receptors detect uncomfortably hot temperatures?

Answer 6

Severe heat receptors are Ad neurons.

Question 7

How do temperature receptors code their information?

Answer 7

Warm receptors increase their firing rate in warm temperatures. Cool receptors increase their firing rates in cool temperatures.

Question 8

What are the transient and steady-state changes in temperature receptors?

Answer 8

The transient change is a rapid increase in firing rate of the receptor as temperature changes in its direction (warm or cool), indicating the rate of change. The steady state change is the increase or decrease in firing rate from baseline that results when the temperature stabilizes.

Question 9

What manipulations distinguish first pain from second pain?

Answer 9

First pain is a sharp, localized, and tolerable pain and is carried by faster Ad fibers. Second pain is a burning, poorly localized, intolerable pain and is carried by C fibers. The localization, or lack there of, of pain on Ad and C fibers is characteristic of those fibers.

Question 10

What stimuli activate polymodal receptors, and what other types of nociceptors are there?

Answer 10

High intensity mechanical, chemical, or thermal stimuli activate polymodal receptors. The other types of nociceptors are cool/warm receptors, hot/cold receptors, and mechanical nociceptors that perceive intense pressure (not touch).

Question 11

What are pain activators and what chemicals function in this way?

Answer 11

Pain activators will actively depolarize nociceptors, generating APs and pain signals. Pain activators include: Bradykinin, Potassium, acids, serotonin.

Question 12

How is bradykinin generated and how does it act in pain stimulus?

Answer 12

Bradykinin is present in the plasma in its zymogen form, kininogen. Cytoplasmic proteases are released from damaged cells and cleave kininogen into BK, a 9AA peptide. BK can then directly activate nociceptors and cause pain stimuli.

Question 13

What are sensitizers and what chemicals function in this way?

Answer 13

Sensitizers reduce the threshold of activation of nociceptors. Sensitizers include: prostaglandins, substance P, ATP, acetylcholine, and serotonin.

Question 14

Where is the VR-1 receptor located and what stimuli activate it?

Answer 14

The VR-1 receptor is expressed on polymodal nociceptors and is activated by the vanilloid moiety on capsaicin.

Question 15

What type of pain information is carried on C-fiber afferents?

Answer 15

C fibers carry the intolerable, burning, and poorly localized “2nd” pain. C-fibers also have the lowest metabolism, and are the last fibers affected by pressure

Question 16

Where is the first synapse in the pain pathway and what neurotransmitter is used?

Answer 16

The first synapse of the pain pathway is in the substantia gelatinosa in the dorsal horn (Rexed’s lamina II). Glutamate is the NT at this synapse, though Substance P is also present when triggered.

Question 17

How does peripheral sensitization occur?

Answer 17

Sodium Channels. Damage to peripheral nerves stimulates regrowth of the neuron. The neuron may develop profoundly different expression, distribution and function of sodium channels which may lead to spontaneous depolarization of the nociceptor.

Question 18

How does central sensitization occur?

Answer 18

Three ways: GABA content/receptors, sprouting & rewiring, glia & immune cells. GABA: Inhibition of pain signals via GABA is critical. Loss of interneurons and reduction in GABA levels leads to a reduction of inhibition in the dorsal horn. Sprouting & rewiring: Loss of C-fibers allows invasion of substantia gelatinosa by Ab afferents, triggering pain response to non-noxious sim (allodynia). Glia & immune cells: TNF, BDNF, KCC2

Question 19

What is the basis for the analgesic action of aspirin?

Answer 19

Aspirin is a COX inhibitor and inhibits the creation of prostaglandins, leading to a reduction of inflammation and nociceptor activation.

Question 20

What is the triple response and which chemicals are responsible for each part?

Answer 20

The triple response occurs as a result of injury (wounds) and consists of a red center (BK), wheal (BK), and flare (Substance P)

Question 21

What causes the red center of the triple response?

Answer 21

Kininogen is cleaved to bradykinin by the cytoplasmic proteases of the damaged cells. BK in turn causes vasodilation leading to the red coloration.

Question 22

What causes the wheal of the triple response?

Answer 22

Bradykinin is a vasodilator and increases the permeability of the vessels, leading to edema. This results in the wheal.

Question 23

What causes the flare of the triple response?

Answer 23

Substance P. Bradykinin at the site of injury will activate C-fibers which transmit the pain signal. C-fibers have multiple ends in the same region, so the AP will also go to these ends and cause release of Sub P. Sub P is also a vasodilator, causing pinkness, and a sensitizer, causing hypersensitivity.

Question 24

What are the locations of action for substance P?

Answer 24

Sub P acts in the dorsal horn and peripherally around injuries. It causes the flare and hyperalgesia.

Question 25

How does the PAG act to modulate pain?

Answer 25

The PAG receives input from cognitive factors (placebo, frontal cortex), systemic morphine, or emotion and stress signals (hypothalamus, amygdala), and triggers the Nucleus Raphe Magnus, which then signals the enkephalinergic inhibitory neurons, blocking pain signals.

Question 26

What is the basis for the placebo effect and stress-induced analgesia?

Answer 26

The placebo effect functions entirely through activation of the PAG/Raphe/Enkephaline system (totally blocked by naloxone). Stress-induced analgesia functions partially through this same system, but partially through another.