Mechanisms of chronic pain

Question 1

How long does pain have to last before it is classed CHRONIC PAIN?

Answer 1

More than 3 to 6 months

Question 2

What is an important factor in pain sensitivity?

Answer 2

Genetics

genes one has regulates how much pain you feel,

some people are more likely to suffer from chronic pain

Question 3

What porportion are Abeta fibres?

What size are they?

What is their response type?

Answer 3

Roughly 1/3rd

Big

Senstivitive mechancoreceptors

Question 4

What porportion are A delta / C fibres?

how big are they?

What is their response type?

Answer 4

ROughly 2/3rds

Small

Thermoreceptors and Nociceptors

Question 5

Are more people insensitive or hypersentive to pain?

Answer 5

Hypersensitive

only a small number of people are insensitive

Question 6

What is Congenital Insensitivity to Pain?

WHat is Anhidrosis?

Answer 6

• Insensitivity to acute tissue damaging stimuli ƒ
• No pain with chronic injury ƒ
• No sweating ƒ
• Variable cognitive impairment ƒ
• Recurrent episodic fever ƒ
• Normal touch, motor function, special senses
• Very specific sensory loss

Anhidrosis - inability to sweat normallu

Question 7

What does NGF (nerve growth factor) do?

Answer 7

Promotes the survival of developing sympathetic and sensory neurones

Question 8

WHat happens in trkA or NGF null mutant mice?

Answer 8

most sensory neurones are lost

mutations in the receptors cause the congenital insensitivity

Question 9

Role of Nav1.7

this is expressed in almost all nociceptors

mutations can affect BOTH extremes of pain sensation

Answer 9

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

Question 10

Nociceptive pain

Stimulus & mechanism

Answer 10

Stimulus : tissue damage

Mechanism: activation of nociceptors

Question 11

Inflammatory pain

Stimulus & mechanism

Answer 11

Stimulus: Inflammatory mediators

mechanism: Periperhal and central sensitization

Question 12

Neuropathic pain

Stimulus & mechanism

Answer 12

Stimulus: Nerve injury

Mechanism: Include ectopic activity, neuro-immune int., central sensitization

Question 13

Dysfunctional pain

Stimulus & mechanism

Answer 13

Both unknown

Question 14

Where dpes Hyperalgesia to a mechanical stimuli occur?

Answer 14

Can also occur outside the site of injury and involves a central mechanism

Question 15

Where does Thermal Hyperalgesia occur?

Answer 15

At the site of injury and has a peripheral mechanism

Question 16

What causes most forms of chronic pain?

Answer 16

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.

Question 17

What may lead to increased excitability of dorsal horn neurons.

Answer 17

various cellular and molecular mechanisms cellular and molecular mechanisms (e.g. LTP, classical’ central sensitisation, glial activation, decreased inhibition)

Altered’CNS’processing

1. Central sensitization
2. Anatomical reorganization
3. Reduced inhibition 4

. Glial activation

Question 18

What is Peripheral Sensitization?

Answer 18

• 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).

Question 19

What is Central sensitization?

Answer 19

• an increase in the excitability of neurons within the central nervous system
• so that normal inputs begin to produce abnormal responses.

Question 20

Neuropathic pain

what is it?

Answer 20

pain arising as a direct consequence of a lesion or disease affecting the

somatosensory system

Question 21

Causes of Neuropathic pain?

Answer 21

• 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

Question 22

Mechanisms of Neuropathic Pain

Answer 22

• 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

1. Central sensitization
2. Anatomical reorganization
3. Reduced inhibition
4. Microglial activation