T2 L7 Physiology of pain Flashcards
What is the definition of pain?
Unpleasant sensory experience accompanied by tissue damage
Accompanied with emotional reaction
Why do we feel pain?
Warning sign
Avoid harmful situations
Prevent further injury or death
Tells us to rest following injury
What are the different sensations of pain?
Deep ache Burning Itchy Stabbing Freezing
What are the 3 classifications of pain?
Nociceptive
Inflammatory
Neuropathic
Describe Aa & Ab fibres
Myelinated
Large diameter
Light touch, proprioception
30-75nm/sec
Describe Aδ
Thinly myelinated
Medium diameter
Light touch, temperature, nociception
5-30nm/sec
Describe C fibres
Unmyelinated
Small diameter
Temperature, nociception
0.5-2nm/sec
What response do Aδ fibres produce?
Sharp pricking pain
What response do C fibres produce?
Slow, dull ache or burning pain
What can activate nociceptors?
Pressure Heat Cold Chemical Tissue damage / inflammation
What do polymodal nociceptors respond to?
Pressure
Temperature
Chemical
Describe the transduction mechanism for pressure
Mechanically sensitive ion channel
Not yet identified in eukaryotic cells
Acid-sensing ion channels (ASIC)
Transient receptor potential (TRP) family of channels
Describe the transduction mechanism for temperature?
Transient receptor potential family of channels
6 transmembrane domains
Activated by aromatic agonists
What activates TRVP1?
Hot temperatures
Agonist is chilli (capsaicin)
Describe the central pain pathway in first order neurons
Enter dorsal horn
Form tract of Lissauer
Synapse in substantia gelatinosa
Glutamate & substance P excite second order neurons
Describe the central pain pathway in second order neurons
Cross in dorsal horn at each level
Ascend in anterolateral column to thalamus
Describe why referred pain occurs
Convergence of visceral & cutaneous receptors on same second order neurons in spinal cord
Brain perceives pain as cutaneous
Describe the central pain pathway in third order neurons
Ascend to primary somatosensory cortex
Encode sensory components e.g. where it hurts & modality
Projections to insula & cingulate cortex to encode emotional components of pain
Pain network
What determines pain experience?
Behaviour
Emotions
Past experiences
What are 2 important regions in the descending regulation of pain?
Periaqueductal grey matter
Rostral ventromedial medulla
Describe the pathway from PAG to dorsal horn
Periaqueductal grey matter projects to rostral ventromedial medulla which projects to dorsal horn
Modulates activity of spinothalamic tract
Describe the inhibition of pain
PAG neutrons excite RVM neutrons which inhibit or excite spinothalamic tract
Serotonergic projects act on dorsal horn inhibitory interneurons
Also parallel noradrenalin pathway
Where are opioids released from?
Interneurons at multiple sites:
- midbrain (periaqueductal grey matter)
- medulla (rostral ventromedial medulla)
- dorsal horn
What do opioids act on?
Inhibitory metabotropic receptors
What chemicals are released by tissue damage?
ATP H+ Serotonin Histamine Bradykinin Prostaglandins Nerve growth factor
What does ATP bind to?
Purinergic receptors (P2X)
What does H+ bind to?
Acid-sensing ion channels
What does serotonin bind to in the activation of nociceptors?
5HT3 receptors
What happens when lactic acid builds up?
1) Tissue acidosis
2) Increased H+
3) Activation of nociceptors
4) Pain
What are the causes of neurogenic inflammation?
Vasodilation
Increased permeability
Activation of mast cells which release histamine causing more inflammation
What is allodynia?
Non-noxious stimuli produces a painful response
What is hyperalgesia?
Noxious stimuli produce exaggerated pain response
What is the benefit of pain hypersensitivity from inflammation?
Pain is more painful
Helps healing by ensuring contact with injured tissue is minimised until repair is complete
What are the mechanisms of pain hypersensitivity?
1) Peripheral sensitisation
2) Central sensitisation
Describe peripheral sensitisation
Increase in responsiveness of peripheral ends of nociceptors
Driven by tissue injury or inflammation
Bradykinin & NGF –> reduce threshold of heat-activated channels.
What happens when bradykinin binds to receptor?
Activation of protein kinase –> phosphorylates TRPV1 –> reduces its threshold –> fires more easily
What does prostaglandin do?
Reduces threshold of sodium channels
