0813 - Pain Pathways and Modulators

Question 1

Explain how the experience of pain is multidimensional

Answer 1

Pain is:
Discriminative (where it hurts vs doesn’t)
Affective - has an emotional element - sad/angry/fear/irritation
Motivational - creates a physical behavioural change
Cognitive/evaluative - appraisal, cultural values, context etc.

Question 2

What is the difference between hyperalgesia and allodynia?

Answer 2

Hyperalgesia is a heightened experience of pain from a noxious stimulus. Allodynia is the perception of pain from an innocuous stimulus.

Question 3

What is the difference between neuropathic and neurogenic pain? Example of each?

Answer 3

Neuropathic - pain that occurs in absence of nociceptor stimulation (e.g. phantom limb pain from central changes).
Neurogenic pain - occurs due to primary damage of nervous system (usually PNS) - e.g. carpal tunnel/nerve impingement. Resolves when the impingement is removed.

Question 4

Outline the difference between pain and tactile pathways

Answer 4

Pain and touch are seperated at the level of the spinal cord - touch ipsilateral via dorsal column to dorsal/cuneate nuclei, synapse, then decussate to thalamus. Pain decussates at-level and travels via spinothalamic direct to thalamus.

Question 5

Describe the fibre types involved in pain/temperature pathways

Answer 5

Transduced by free nerve endings, and carried by narrow A-delta (myelinated - sharp, lochalised hot pain etc) and C (unmyelinated - slow, mechanical/irritating/aching) fibres. C-type pain persists long after stimulus is removed.

Question 6

Describe the different pain/temperature sensations and outline how these are discriminated by free nerve endings

Answer 6

Noxious heat -
Mechanical
Chemical
It all depends on the type of receptor that is activated (hence why capsaicin perceived as hot)

Question 7

What are the major CNS pathways that contribute to the various dimensions of pain?

Answer 7

Discriminative to S1 - VP thalamus
Others through medial thalamic nuclei.
Spinoreticular tract (medial pain pathway)
Spinomesencephalic
Anterior cingulate
Insular cortex

Question 8

Describe the Discriminative pain pathway and its trajectory.

Answer 8

Main one. Goes to S1.
Body pain goes to VPL of thalamus. Lower body is more lateral, upper body is more medial (because crossing immediately, so wedges it out to the side). Ascends to spinal lemniscus, then to VPL thalamus.
Face/Head Goes to VPM - enters into spinal trigeminal tract, travel up/down segments until relaying in spinal trigeminal nucleus. Cross midline and form trigeminothalamic tract (carrying pain, temp and some tactile), which joins medial lemniscus and synapses in VPM thalamus.

Question 9

Describe the Spinoreticular tract (medial pain pathway) and its trajectory

Answer 9

Responsible for arousal/alert CNS of painful event. Pain enters through dorsal horn, ascends up ventral/lateral ‘corner’ to reticular formation, which projects to thalamus. Some reticulo-spinal projections can then moderate pain transmission.

Question 10

What is the Spinomesencephalic tract for pain?

Answer 10

Spinal projections to many regions in midbrain. Key structure is periaqueductal grey - coordinates an appropriate behavioural/emotional/autonomic response for the type of injury (e.g. invigoration on skin pain, quiescence on deep pain). PAG projects to amygdala (emotional response), hypothalamus (autonomic response), and medullary raphe (analgesia).

Question 11

What areas of the brain/brainstem are important for the autonomic response to pain?

Answer 11

Amygdala - conditioned fear memory
Hypothalamus - Autonomic NS regulator
Periaqueductal grey - Behavioural, autonomic NS, and pain regulation responses are orchestrated
Superior colliculus - head orienting reflex
Reticular formation - arousal.

Question 12

What areas of the brain map to which types of pain?

Answer 12

S1 - discriminative
Insular - interoceptive aspects - perception of a painful event - could I tolerate more or less of this?
Amygdala - Fear
Anterior cingulate - affective Emotional response and ‘unpleasantness’ of pain.

Question 13

How does the brain perceive visceral pain?

Answer 13

Travels via SY pathways, but in an efferent manner ‘sharing the nerves’. Then synapses in dorsal horn onto ST tract neurons.

Question 14

Describe the key elements and outline the mechanisms that contribute to peripheral sensitisation

Answer 14

Various inflammatory chemicals increasing excitability of nerve endings.
Neuronal elements - Substance P, ATP, Calcitonin gene-related peptide
Non-neuronal (cellular) - H+; arachidonic acid, bradykinin, histamine etc.
Gate control theory - stimulation of mechonoreceptors can over-ride the C fibres.

Question 15

Describe the key elements and outline the mechanisms that contribute to central sensitisation

Answer 15

Increased excitability of neurons (usually dorsal horn), resulting in transmission of sub-threshold nociception, increasing pain sensitivity. Can be by increased ion channels/receptors, long term potentiation, reduced GABA/Gly activity in dorsal horn.
Abnormalities can result in neuropathic pain.

Question 16

Describe the key elements and outline the mechanisms that contribute to central pain modulation

Answer 16

Modulated by descending inhibition of ascending pathways. PAG plays a central role, including via opioids, endocannabinoids, and noradrenaline. Inputs converge on lamina I and II.

Question 17

List key endogenous neurotransmitters that are involved in pain modulation and outline their mechanism of action

Answer 17

Endogenous Opioids - G-protein coupled Pre (Ca++) or post(K+)-synaptically to reduce APs.
Endocannabinoids - Anandamide - goes back from post-synaptic to presynaptic neuron and reduces release.
Noradrenaline