#10 Pain: A Neurobiological Perspective

Question 1

What is pain?

Answer 1

An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

Question 2

What is nociceptive pain?

Answer 2

It is the autonomic pain response, it involves the withdrawal reflex.
First you get noxious stimuli (heat/cold/pressure/chemical) which activates the nociceptor sensory neuron in the spinal cord, and then you get the response.
The response is adaptive, has a high pain threshold, and it is an early warning system (protective, and serves for survival)

Question 3

What is pathological pain?

Answer 3

This is the spontaneous pain response, you have pain hypersensitivity here.
First you get neuropathic pain (neural lesion, positive and negative symptoms), which activates peripheral nerve damage and abnormal central processing.
This is maladaptive and has a low pain threshold, is it reacting to stimuli that is not painful but we think it is. It often occurs post damage from injury, trauma and disease processes

Question 4

What is allodynia?

Answer 4

Pain due to a stimulus that normally does not cause pain

Question 5

What is neuropathy?

Answer 5

Disturbance in function or pathologic change in a nerve

Question 6

What is central pain? What is neuropathic pain?

Answer 6

Central pain: pain caused by a 1 degree lesion or dysfunction in the CNS
Neuropathic pain: pain caused by a 1 degree lesion or dysfunction in the nervous system

Question 7

What is dysesthesia? What is paresthesia?

Answer 7

Dysesthesia: unpleasant abnormal sensation
Paresthesia: abnormal sensation, whether spontaneous or evoked

Question 8

What is hyperesthesia? Hypoesthesia?

Answer 8

Hyperesthesia: increased sensitivity to stimulation
Hypoesthesia: decreased sensitivity to stimulation

Question 9

What are the four divisions of the spinal cord?

Answer 9

Cervical (C1-C5)
Thoracic (T1-T12)
Lumbar (L1-L5)
Sacral (S1-S2)

Question 10

Where do your primary sensory neurons lie?

Answer 10

They lie in the dorsal root ganglion and they send info from the outside world to the brain and spinal cord

Question 11

What are the two types of primary sensory neurons?

Answer 11

1. Alpha A and Alpha B (large light): discriminative touch proprioception
2. Alpha delta and C (small dark): pain and temperature response

Question 12

What are some characteristics of the alpha a and alpha b primary sensory neurons?

Answer 12

They are heavily myelinated, have a large diameter, and they are sensitive to proprioception and light touch

Question 13

What are some characteristics of the Alpha delta fibre?

Answer 13

They are lightly myelinated, medium diameter, responsible for nociception (mechanical, thermal, chemical).

Question 14

What are some characteristics of the C fibre?

Answer 14

Unmyelinated and small diameter, therefore slow, innocuous temperature and itch, nociception (mechanical, thermal, chemical)

Question 15

Where do the different primary sensory neurons project to in the dorsal horn?

Answer 15

Alpha B fibers project to the deep lamina (3/4/5), the alpha delta fibers project superficially (1/2) and deep (4), and the C nociceptors are superficial.
Interneurons connect lamina 2 to the WDR (wide dynamic range)

Question 16

What are the central projections for primary sensory neurons?

Answer 16

Lamina 1 neurons have projections to the STT
Lamina 2 interneurons connect with WDR and Lamina 5
WDR axons contribute to the STT
STT: spinothalamic tract

Question 17

What is the specificity theory of pain?

Answer 17

A specific pain system carries messages from pain receptors in the skin to a pain center in the brain.
Originally formulated by Descartes in 1664
Suggest a direct, invariant relationship between a psychological sensory dimension (what we sense as pain), and a physical stimulus

Question 18

What is the Gate Control Theory of Pain?

Answer 18

Idea that pain can be modulated. A gate within the spinal cord can be opened or closed.
There are gate cells which are connected via inhibition to T cells. When the gate cell is activated by alpha A and alpha B fibers, it inhibits the T-cell, effectively closing the gate therefore pain cannot get to the brain and it not sensed. When the gate cell is inhibited by alpha delta and C fibers, the T-cell is active and pain can get through and into the brain

Question 19

What is sensitization?

Answer 19

When the response to pain is amplified (hyperalgesia) or when previously innocuous stimuli seem painful (allodynia)
There are two levels of sensitization: peripheral and centra;

Question 20

What is peripheral sensitization?

Answer 20

Pain activates an internal pathway causing the release of many inflammatory molecules called an inflammatory soup.
These activate second messengers which modify ion channels by phosphorylation , thus they can open at lower voltage and remain open longer. This is boosting excitability/activity, and causes pain at lower stimulation and lasts for longer

Question 21

What is central sensitization?

Answer 21

Normally you have regular EAA release, activation of AMPARS and MNDARS are silent due to an Mg block.
Central sensitization ENHANCES EAA release, neuropeptides and recruitment of NMDARS.
You also get enhanced Ca+ entry via phosphorylation (acute) and gene transcription (long term)
This results in reduced threshold and increased output

Question 22

What is activity dependent central sensitization?

Answer 22

No response to “test stimuli” such as light touch (activated alpha a and b), then you get a barrage of conditioning stimuli (c-fibres mimic tissue injury), and the cell will now respond to “low threshold/light touch stimulus, and oultasts the conditioning train