Mechanisms of chronic pain Flashcards
(22 cards)
How long does pain have to last before it is classed CHRONIC PAIN?
More than 3 to 6 months
What is an important factor in pain sensitivity?
Genetics
genes one has regulates how much pain you feel,
some people are more likely to suffer from chronic pain
What porportion are Abeta fibres?
What size are they?
What is their response type?
Roughly 1/3rd
Big
Senstivitive mechancoreceptors
What porportion are A delta / C fibres?
how big are they?
What is their response type?
ROughly 2/3rds
Small
Thermoreceptors and Nociceptors
Are more people insensitive or hypersentive to pain?
Hypersensitive
only a small number of people are insensitive
What is Congenital Insensitivity to Pain?
WHat is Anhidrosis?
- Insensitivity to acute tissue damaging stimuli
- No pain with chronic injury
- No sweating
- Variable cognitive impairment
- Recurrent episodic fever
- Normal touch, motor function, special senses
- Very specific sensory loss
Anhidrosis - inability to sweat normallu
What does NGF (nerve growth factor) do?
Promotes the survival of developing sympathetic and sensory neurones
WHat happens in trkA or NGF null mutant mice?
most sensory neurones are lost
mutations in the receptors cause the congenital insensitivity
Role of Nav1.7
this is expressed in almost all nociceptors
mutations can affect BOTH extremes of pain sensation
Deletion of Nav1.7 in mice
- no inflammatory pain behaviour shown
Point Mutations in Nav1.7
- lead to primary erythomelalgia and Paroxysmal Extreme Pain Disorder
Nociceptive pain
Stimulus & mechanism
Stimulus : tissue damage
Mechanism: activation of nociceptors
Inflammatory pain
Stimulus & mechanism
Stimulus: Inflammatory mediators
mechanism: Periperhal and central sensitization
Neuropathic pain
Stimulus & mechanism
Stimulus: Nerve injury
Mechanism: Include ectopic activity, neuro-immune int., central sensitization
Dysfunctional pain
Stimulus & mechanism
Both unknown
Where dpes Hyperalgesia to a mechanical stimuli occur?
Can also occur outside the site of injury and involves a central mechanism
Where does Thermal Hyperalgesia occur?
At the site of injury and has a peripheral mechanism
What causes most forms of chronic pain?
most forms of chronic pain are underlain by plastic changes in peripheral nociceptors and interneurons of the dorsal horn of the spinal cord, which lead to increased nociception.
What may lead to increased excitability of dorsal horn neurons.
various cellular and molecular mechanisms cellular and molecular mechanisms (e.g. LTP, classical’ central sensitisation, glial activation, decreased inhibition)
Altered’CNS’processing
- Central sensitization
- Anatomical reorganization
- Reduced inhibition 4
. Glial activation
What is Peripheral Sensitization?
- reduction in threshold and an increase in responsiveness of the peripheral ends of nociceptors
- high-threshold peripheral sensory neurons that transfer input from peripheral targets (skin, muscle, joints and the viscera) though peripheral nerves to the central nervous system (spinal cord and brainstem).
What is Central sensitization?
- an increase in the excitability of neurons within the central nervous system
- so that normal inputs begin to produce abnormal responses.
Neuropathic pain
what is it?
pain arising as a direct consequence of a lesion or disease affecting the
somatosensory system
Causes of Neuropathic pain?
- Infectious
- e.g. HIV, Post herpetic neuralgia
- Metabolic/Nutritional
- e.g. Diabetic, alcoholic neuropathy
- Neurotoxity
- e.g. Cisplatin, taxol, vincristine
- Truamatic
- e.g.entrapment, transection, surgical damage
- Central lesions
- e.g. spinal cord injury, stroke
Mechanisms of Neuropathic Pain
- Altered CNS procressing
- Central glia contribute to chronic pain
- Altered gene expression
- Ectopic activity
- Change in retrograde transport of trophic factors
- increased injury factors
Also
- Central sensitization
- Anatomical reorganization
- Reduced inhibition
- Microglial activation
