Week 3 Part 2 Flashcards
What is the implications of Hyperalgesia?
Tissue damage
Adaptive Change in nociceptors “amplification”
What is the implication of Allodynia?
Damage to the nervous system
Pathophysiological change in sensory coding “switching”
Primary Hyperalgesia
At the site of injury
Secondary Hyperalgesia
More distant site
What happens in the distal oesophagus?
Sensitisation of proximal site to acid
What is referred Hyperalgesia?
Felt at a site distant from the site of origin
More pronounced in subcutaneous tissue than in skin
Related to duration and intensity of episodes of visceral pain
What are examples of central sensitisation?
Allodynia
Hyperalgesia
Secondary Hyperalgesia
Referred Hyperalgesia
What is example of peripheral sensitisation?
Hyperalgesia
Secondary Hyperalgesia
Sensitisation of the dorsal neurons
What is normal sensitive - normal threshold of pain?
30-40ml of Mercury
Hypersensitive patients
15/20ml of Mercury
What is peripheral sensitisation?
Increased sensitivity to an afferent nerve stimuli
Occurs after there has been an injury or cell damage to area and produce a flare response to nociceptors producing lots of neuropeptides
What are the different types of mediators?
Tissue (epithelial and stromal for support)
Blood supply
Immune cells
What are examples of classical mediators ?
Bradykinin Prostaglandin ATP/Adenosine 5-HT Histamine
What are examples of immune mediators?
Cytokines
Chemokines
Processes
Protease activated receptors
Gain of system
Sensitisation
Form protective reflexes
How will we sensitise or stimulate these nerves?
Enhance the activity in the channels that depolarise the ending
Reduce the activity in the channels that hyperpolarise the ending
Dial up activities in TRP
Dial down activities in KTP channels
What happens during tissue injury?
Mediators released from certain cells
Activate GPCR
Stimulus transduction mechanism
Modulate the activity in those translucent channels
What is an agonist of TRP A one channel?
AITC
Inward current - response desensitises repeated application
What is TREK-1 and TRAAK activated by?
Arachidonic scid
What is Trek-1 inhibited by?
Gq and Gd coupled GPCRs I.e PGE2
What switches on and enhances current in KTP channels?
AA
What is the function of prostaglandin?
Sensitise nociceptors
What happens in the presence of PGE2?
Reduce the current mediator through KTP channel
How can we modulate the activity in transducer channels?
Amplify gain in sensory nerve endings
Tune the response to initial activation through transducer channels
Several subtypes - voltage hated channels Nav1.9 on one side and low voltage activated Cav 3,2 channels on other
What is the function of transducer channels?
Move calcium into nerve endings
What is NAv1.9?
Sensitisation to inflammatory mediators
What has no effect on Nav1.9 current?
CAMP
What is Kv 7.x inhibited by?
Inflammatory mediators
What gives brisk activation of sensory nerves?
Beta
Block it with TTX
Implication of ruthenium red
Block the enhancement of TNF alpha
How do we promote excitation?
Dialling up activity in transducer channels
What are examples of inhibitory GPCR?
Opioids/endocannabinoids
Somatostatin/galanin
MGluR/P2Y
Gi/o coupled - decreased CAMP
What is helping keep our sensory nerves in check?
Releasing certain tone of endogenous opioids
