Week 5 Flashcards
What is neuropathic pain?
Caused by damage or disease affecting the nervous system
Described as shooting or burning pain
What are symptoms of Neuropathic pain?
Shooting and burning pain
Tingling and numbness
What occurs after injury?
Lose function/ motor function
Lose sensory innervation
Where is Dorsal root ganglion located?
Spinal column and level lumbar 4,5,6
What do you find peripherally?
Spinal nerve and contribute to sub-sciatic nerve
When is neuropathic pain common?
After partial injuries
What is the role of Dorsal root Ganglia?
Modulation of peripheral and central sensory processing that include:
Inflammation
Somatic pain
Development of neuropathic pain
How do you partially injure a nerve?
Ligate/ cut some sciatic nerve
What is chronic construction injury?
Putting ligatures around the nerve
Cause inflammatory action
Constricts it
What is chronic constriction injury model?
Left sciatic nerve of a rat is ligated causing inflammation and swelling
Model was evaluated via paw mechanical withdrawal latency and DRG immunohistochemistry
What is the features of chronic constriction injury model?
- Investigate both pathophysiology and potential thereapeutic agent for treatment of neuropathic pain
- Behavioural signs of spontaneous pain can be observed e.g. limping of hind paw
What is the symptoms of chronic neuropathic pain?
Spontaneous pain
Paraesthesia
Allodynia
Hyperalgesia
What is sciatic nerve injury?
Loss of movement
Lack of sensation
What does sciatic nerve Contain?
Motor and sensory axon
What is peripheral sensitisation?
Increased sensitivity to afferent nerve stimuli
What is central sensitisation?
Condition of the nervous system that is associated with development and maintenance of chronic pain
What happens to the distal portion of nerve after an injury?
The axons will die
It will be cut off from the cell body
What is a neuroma?
A collection of growth cones
What are the changes in the peripheral nerve?
Distal portions of the axon die
Proximal portions attempt to regrow in the direction of target
What happens when axon regrowth is unsuccessful?
Formation of a focal tangle of proliferated growth comes
Together with massive Schwann cell proliferation
In-migration of inflammatory cells forming a neurons
What is the first active inflammatory response?
Infiltration of the neutrophils
What would be an inflammatory mediator that would cause peripheral sensitisation?
Prostaglandin
Histamine
Protons/ATP
Why is inflammatory response required?
Tissue to heal
Bring more blood into the region of injury
Take away toxin substances
What is required for maintenance for functional recovery?
Chenophlayphin interleukin 2
What is the role of clonidate?
Reduction in hypersensitivity and repair
What is wallerian (orthograde) degeneration?
Active process of degeneration that results when a nerve fibre is cut or crushed and the part of axon distal to injury degenerates
No metabolic support of that portion
What happens when degeneration occurs?
The myelin sheath breaks down
What does wallerian degeneration show?
Mouse can have axons that are active
Able to propagate action potential up to 30 days
Axonal degeneration can occur before what other events?
Myelin sheath breakdown
Accumulation and axonal regeneration
What is maintaining the axon?
Peripheral tissue
Retrograde degeneration
Loss of trophic support from peripheral target tissue
What are the retrograde degeneration/changes?
Loss of trophic support from peripheral target
Signal from degenerating axons
Within hours, soma swells, reorganisation of nucleus and RER
Synaptic transmission proteins goes down
Growth associated proteins go up to enable regeneration
Growth cones of neurites elongate
What does C fibre show?
Sprouting of intact axons going into a region they do not normally convey signals from
What can damages axons do and what can intact axons do?
Damaged axons go to where it should
Intact axons can sprout and take over function of denervated area
What stimulates sprouting?
Nerve growth factor
What are all nociceptors cells dependent on?
NGF
What receptors does NGF act through?
Neurotrophin receptors
Neurotrophin receptor kinase A
What is an high affinity receptor?
TRAK A
What is an accessory receptor ?
P75
What happens if we block NGDF treatment?
The sprouting does. It occur putting more NGF into system
Physiologically, where does NGF go up in?
Denervated skin in target tissue
What is C-fos?
Immediate early gene that’s activated quickly at the transcription of that factor
What is Paraesthesia?
Pins and needles
What is Hyperpathia?
Someone in chronic pain continually
What is Rhizotomy?
Surgical procedure that severe nerve roots in spinal cord
What is spontaneous activity generated by?
Cell body
Neuroma
What are neuroma?
Mechanosensitive
Pressing a neuroma causes action potential to go from area of injury
Originated from DRG
What does 20% of the injured muscle afferent have?
Large diameter myelinated fibres
No cutaneous afferent firing
What is peripheral nerve spared injury prep?
Cut some of them and leave others intact The area will still be innervating Detect signal Record from one site of injury Determine what’s active or not
What are low level C fibres essential for?
Central sensitisation
Where does inputs from C fibres constantly go into?
Spinal cord
Lead to alterations in networks of spinal cord
Plasticity in spinal cord - easier to excite those second order neurons
What factors are released centrally by C fibres that elicit central sensitisation
Peptide
Trophic factors
What is polyneuropathy?
Damage or disease affecting peripheral nerves in roughly the same area in both sides of body
What increases in the neuroma?
NaV1.3
What are important for bursting patterns?
NaV1.8
What regulates NaV1.3?
GDNF
What is asphalting connections?
Demyleinated regions can send action potential ultimately down both the intact as well as injured afferent
What is crossed after-discharge?
Neurotransmitters at the dorsal root ganglion May affect the function of intact axons, cells firing
What goes up around the cell body?
Potassium levels
Impact on threshold of cell
What is the consequence of down regulation of potassium channels?
Make cells more sensitive
What causes neuropathetic pain type syndrome?
siRNA knock down
What is Chromatolysis?
Packets of RER in normal neurons (missal substance) that becomes more diffused ultimately within an injury
Messenger RNA tend to go more peripherally around cell
What causes more cell death?
Lesion close to the cell bodies
Injury
Cell side changes and generally gets smaller
What is stereology?
Assessing particularly small units, more or less randomly in different segments but adding all of the segments together in each of sample
What happens if EPAC is knocked out?
There is less Allodynia response through injury
