Neural Basis of Pain

Question 1

Chronic pain is pain that lasts for more than […]

Answer 1

3 months

Question 2

Describe how pain signaling is “gated” in the spinal cord and why rubbing your elbow if you just bumped it helps alleviate your pain.

Answer 2

If you bump your elbow and do nothing, the c fibers in your elbow will send a pain signal via the anterolateral system to a second order neuron in the dorsal horn of the spinal cord. They will also simultaneously inhibit an interneuron that talks to the second order neuron, preventing the interneuron from modulating the pain response. As such, the signal for pain is transduced up to the brain and you feel pain.

If you bump your elbow and rub the area where you bumped it, the c fibers in your elbow will send a pain signal via the anterolateral system to a second order neuron in the dorsal horn of the spinal cord. They will still simultaneously inhibit the interneuron that talks to the second order neuron, however now mechanoreceptors (A_beta) in the skin also are able to talk to the interneuron and stimulate it. This stimulation is enough to overcome the inhibition from the C fiber and the interneuron is excited, it releases GABA onto the second order neuron and there is a reduction in the pain signal that is sent to the brain.

Question 3

What is the spinoreticular tract?

Answer 3

Question 4

Once pain information ascends via the spinothalamic tract to the thalamus, does it just stop at the thalamus or does it get distributed further?

Answer 4

Goes to prefrontal cortex, insula, somatosensory cortex (primary and secondary)

Question 5

Once information ascends to the cortex via the spinothalamic tract or to the subcortical sturctures via the spinoreticular tract, does it just remain there in those areas or does it go somewhere else?

Answer 5

Once pain information reaches the prefrontal cortex, the insula, and the somatosensory cortex via the spinothalamic tract or the amygdala and the hypothalamus via the spinoreticular tract, those areas then send descending projections that all converge in the periaqueductal grey matter (PAG) prior to modulation of activity in the spinal dorsal horn.

Question 6

Once the signals from cortical and subcortical areas converge on the PAG, the PAG sends projections to where?

Answer 6

Sends descending modulatory projections to monoaminergic nuclei in rostroventral medulla, i.e. raphe nucleus and locus coeruleus

Question 7

Stimulation of the PAG has been shown to produce […]

Answer 7

Analgesia

Question 8

The raphe nucleus produces […] and the locus coeruleus produces […]

Answer 8

Serotonin

Norepinephrine

Question 9

Once signals reach nuclei of the RVM, where do they go after that?

Answer 9

They descend to the dorsal horn of the spinal cord and synapse on an interneuron that releases enkephelins

Question 10

• What is enkephalin?
• When serotonin and NE are released onto the enkephalinergic interneuron:
  
  • What is the result on the second order ascending neuron in the dorsal horn of the spinal cord?
  • What is the result on the first order sensory neuron in the dorsal horn of the spinal cord?

Answer 10

• Enkephalin is an endogenous opioid
• Second order neuron - inhibited by enkephalin
• First order neuron - enkephalin inhibits

Question 11

What effect do opoids have on the PAG?

Answer 11

They activate it directly to enhance output of serotonin and NE into spinal cord

Question 12

What effect does morphine have on the primary and secondary neurons in the spinothalamic tract?

Answer 12

Primary

• Morphine is inhibitory, so it reduces the release of substances from the primary neuron, namely glutamine and substance P (neuropeptide) leading to a reduction in pain

Secondary

• Inhibited directly by morphine

Question 13

Opioids

• Main effect?
• Common side effects (8)
• Effect of withdrawal?

Answer 13

• Analgesia
• Nausea/vomiting, sedation, mood change, miosis, respiratory depression, neuroendocrine effects, constipation, temp changes
• When you take something for a long time and then you stop taking it, the effect will be the opposite of what the medication did. As such, withdrawal from opoids results in hyperalgesia and anxiety

Question 14

Describe in general how endogenous canabinoids are produced and what their effect is on the NS.

Answer 14

Presynaptic neuron releases Glu or GABA, binds to post synaptic neuron, results in AP in post synaptic neuron, influx of Ca2+, formation of Anandamide which is then pumped out of post synaptic neuron into synaptic cleft. Anandamide binds to CB1 (in CNS) receptor on presynaptic neuron, modulates signaling pathway that inhibits entry of Ca2+ into presynaptic neuron and reduces the firing of that neuron. This can ultimately lead to the reduction of substances that signal pain and inflammation in the body.

Question 15

True or false: pain is proportional to the nociceptive input.

Answer 15

False - pain is highly subjective. Same 2 people can have same input and feel different levels of pain based on memories, emotions, other pathologies they have or have had in the past, genetics, and other cognitive factors.

Question 16

What is the effect of emotions and cognition on pain experience?

What about pain on emotions and cognition?

Answer 16

Emotions and cognition can either inhibit or increase pain.

Pain decreases our emotions and cognition.

Question 17

What is the role of the amygdala in pain processing?

Answer 17

It is important for the emotional evaluation of a painful stimulus and is partly responsible for the feeling of dysphoria (unease/dissatisfaction) that we get with pain. It is also important in the placebo effect because the expectation of getting better with placebo is processed by the amygdala.

Question 18

What is the placebo effect?

Answer 18

Pain relief that comes with the assumption that one has received something that relieves pain. It is the expectation of pain relief.