8 Pain Mechanisms and Pathways

Question 1

What is pain?

Answer 1

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.
It is more like hunger and thirst than vision or audition - a drive rather than a sensation.

Question 2

List 5 classes of mechanoreceptors

Answer 2

Free nerve endings = nociceptors

Question 3

List 4 classes of nociceptors and 2 types of nerve fibres

Answer 3

Thermal, mechanical, polymodal, silent

• A delta and C fibres

Question 4

LIst the differences between A delta and C fibres

Answer 4

A delta are thicker and have myelination
C are thin and are demyelinated
*myelin increases conduction

A delta are closer to the skin and signal the first localised are sharp pain
C produce the delayed throbbing and aching secon pain

Question 5

What is Lewi’s Triple Response?

Answer 5

Retrograde activation of sensory fibres causes NTs to leak out at peripheral end. These cause vasodilation and the plasma extravasates, increasing pain sensitivity at the site.

Question 6

Describe the substances released at the site of injury and the process leading to peripheral sensitisation

Answer 6

• Tissue damage triggers local release of bradykinin, PGs and K+
• this activate nociceptors and retrograde activation of collaterals triggers release of Substance P

Substance P -> mast cell degranulation -> histamine -> vasodilation -> plasma extravasation -> more sensitisation of nociceptor -> spreading of response from site of injury

If sensitisation soup continues sensitising unchecked, pathological primary:

Hyperalgesia: noxious stimuli become more noxious
Allodynia: innocuous stimuli become painful

Question 7

Which lamina in the spinal cord do nociceptor fibres project into?

Answer 7

A delta fibre mainly into lamina 1 and 5

C fibres mainly into lamina 2

Question 8

What is central sensitisation?

Answer 8

Activation of slow (Glu - AMPA) and fast (SP - NK-1) post synaptic elements primes the activation of the medium speed element. THe plug is removed and Glu can bind to NMDA. It will fire uncontrollably - prolonged activation can trigger genomic changes leadnig to neuropathic pain.

Question 9

How can we prevent/reverse central sensitisation of pain?

Answer 9

2 binding sites on the calcium NMDA channel can be targeted

• one by tricyclic antidepressants
• one by Ketamine

Question 10

Which neurons are most vulnerable to death caused by overactivation?

Answer 10

GABAergic inhibitory neurons are most vulnerable to the neurotoxicity caused by overaction (note this activation may be happening without any trigger - internally driven pain)

Question 11

How does pain get referred?

Answer 11

Convergence of primary afferent fibres onto common pools of spinal cord neruons - a mistake is made. Makes decisions based on what it is used to, therefore it thinks it is from the skin rather than a deep organ it has never heard of before.
Can also accidently result in a reflex of SNS or motor neurons.

Question 12

Name the ascending pathways of pain

Answer 12

Fibres from spinal cord lamina (below the head) cross the midline and ascend in the anterolateral tract.

Subsets of this tract include:
spinothalamic - those that travel to the thalamus
spinoreticular and spinomesencephalic - integrate affective and motivational components of pain

Pain form the head is relayed through the trigeminal nerve in the ventral trigemino-thalamic tract

signals are then sent to S in a somatotopic map