Pain

Question 1

How is pain generated?

Answer 1

• Tissue injury/pain signal (mechanical, thermal, chemical) - mediates released - these go to stimulate nociceptors on c (slow, throbing) and a (fast, intense) fibers (convert external painful stimuli to electrical signals (action potential)
• Get an injury stimulus (mechanical, thermal and chemical pain), C (slow, throbing) and A fibers (fast, intense) (have nociceptors on end) will be stimulated.
• Primary afferents go to dorsal horn then synapse in brainstem, then go to thalamus and sensory cortes
• Perception of pain - in brain - reticular system, limbic system and somatosensory cortex

Question 2

How is pain modulated in the body (gate control theory)

Answer 2

A gate in the dorsal horn will modulate the afferent nerve impulses

• A non-painful stimulus can block the transmission of a noxious stimulus
• there are special inhibitory inter-neurons in the spinal cord - these keep the gate closed, they make enkephalin which is an endogenous opiod which blocks pain (blocks neurotransmitter release from C and A fibers ) - keeps gate closed
• this is where opiods can work

Question 3

Modulation of pain (from brain)

Answer 3

Stimulation of the areas in midbrain that sense pain will then activated neurons that project to the pons and medulla.
There will be descending nuerons from pons and medulla release noradrenaline and 5-HT respectively, stimulate inhibitory interneurons in the DH that will release enkephalin

Question 4

What is wind up?

Answer 4

• Increased AP output form the dorsal horn cells
• in response to sustained low frequency input from nociceptive affernets via C fibers to the DH neurons
• THen senstation to pain will be heightened
• Receptors on DH neurons are stimulated by increased glutamate and substance P produced by C fiber terminalds due to their continuous stimulation for an extended period of time from peripheral receptors
• DH neurons become more responsive lowering thershold of all its inputs resulting in central sensiztizaiton
• ketamine and methadone are NMDA receptor inhibitors and prevent windup and may play a central role in managing chronic pain

Question 5

Nociceptive pain pathway
Nueropathic pain
Inflammatory pain

Answer 5

Nociceptive pain

• Tissue damage - mediators released
• these will go to nociceptors and activate them - get action potential down
• go to axon into lamina 1 and 2 -then to brain
• glutamate to AMPA receptor in lamina 1, 2

Neuropathic pain - damage to neuronal structure - usually opiod resistant

• Peripheral - burning, tingling, pins and needles
• Central - thalamic pain syndrome

Inflammatory pain
-post traumatic pain - which includes tissue damage, inflammatory mediators

Question 6

Non-neurogenic inflammation vs neurogenic inflammation

Answer 6

Non- involves release of inflammatory substances from blood vessels
-day 2 - get more pain - perceived as worse due to sensitisation

Nuerogenic - release of neuropeptides (e.g substance P) from C-fibers terminals - peripheral sensation (primary hyperalgesia)

• after pain has been felt - will send down stimulation - axon reflex
• will secrete neuropeptides , these will stimulate the mast cells and blood vessels to vasodialte, - inflammation response
• will also stimulate inflammatory cells in the area, to release more inflammatory mediators
• these will lower therhsold of peripheral thershold - and if it continues then will get central senstiitsaion

-both lead to lowering the threshold of receptors leading to hyperalgesia