Physiology of Pain

Question 1

What are the 3 forms of pain?

Answer 1

• Nociceptive
• Inflammatory
• Pathological

Question 2

What are pain points of origin?

Answer 2

• Skin - well localised
• Muscle - poorly localised
• Viscera - poorly localised and diffuse, often referred to somatic structure

Question 3

What are nociceptors?

Answer 3

Specific peripheral primay sensory afferent neurons

Cell body location: dorsal root ganglia, trigeminal ganglia (TG)

First order neurons that relay information to second order neurons in CNS by synaptic transmission

Question 4

Nociceptive Pain

Answer 4

• High threshold
• Adaptive
• Early warning system; withdrawal reflex, unpleasant, adverse emotions, inscribes memeories

Question 5

Inflammatory Pain

Answer 5

• Adaptive and protective (discourages physical contact)
• Activation of immune system (macrophages, mast cells, neutrophils, granulocyte)
• Pain hypersensitivity + allodynia
• Reduction in inflammation required to reduce pain
• Low threshold pain

Question 6

Pathological Pain

Answer 6

• Maladaptive
• Not protective
• Abnormal nervous system function
• Low-threshold pain
• Spontaneous pain, pain hypersensitivity

Neuropathic pain - ie neural lesion/stroke -> peripheral nerve damage

Dysfunctional pain - normal peripheral tissue and nerves (synaptic plasticity? strength of connection of nociceptor with second order neuron may be increased)

Question 7

Congenital Insensitivity to Pain (CIP)

Answer 7

Loss of function mutations (missense, or in frame, deletions) in gene SCN9A that encodes Nav1.7 highly expressed in nociceptive neurons

Nav1.7 - voltage activated Na channel

Question 8

Primary sensory afferents

Answer 8

A alpha - thick myelination, fast conduction velocity (80-120), sensory receptor: proprioceptors of skeletal muscle

A beta - moderate myelination, relatively fast conduction velocity, sensory receptors: mechanoreceptors of skin

A delta - thin myelination, slow conduction, sensory receptors: pain, temperature

C - no myelination, very slow conduction, sesnory receptors: temperature, pain, itch

Question 9

What does Substance P do?

Answer 9

• Vasodilation and extravasation of plasma proteins (promotes formation of bradykinin and prostaglandins
• Release of histamine from mast cells
• Sensitisation of surrounding nociceptors
• May facilitate activation of NMDARs

Leads to hyperalgesia and allodynia

Question 10

What does GGRP do?

Answer 10

Calcitonin gene related peptide

Induces vasodilation

Leads to hyperalgesia and allodynia