Pain & Chronic Pain

Question 1

What is Pain?

Answer 1

Pain is “an unpleasant sensory and [or] emotional experience associated with actual or potential tissue damage…”
Some key terms:
Nociceptive pain: pain arising from tissue damage (aka adaptive pain)
Neuropathic pain: pain arising from damage to the damage-reporting system itself in the nervous system.
- Spontaneous generation of pain.
Other pain: pain arising from neurological dysfunction, not damage.
Pain does not exist in your body, it can only exist in your brain. That is where you “feel” pain!

Question 2

How do we perceive pain?

Answer 2

It starts with pain receptors  nociceptors
A nociceptor is a sensory neuron that responds to damaging stimuli;
Sends ”possible” threat signal to spinal cord and brain;
If the brain perceives this threat as credible, it will create the sensation of pain, and initiate a cascade of events to deal with the pain accordingly  process is called nociception.

There are different types of nerve endings that can sense different types of noxious stimuli:
Free nerve endings are embedded in the tissues.
Encapsulated nerve endings synapse with tissues.

Question 3

Noxious stimulus

Answer 3

Noxious stimulus = tissue injury ≠ pain
Cutting;
Crushing
High or low temperature;
Chemical irritants;
Stretching;
Ischemia;
Inflammation

Question 4

Afferent Pain Pathways

Answer 4

Noxious stimuli act on nociceptors to communicate information.
- Ion channels in nerve endings;
- Translate physical stimulus into electrical
signal.
Action potentials are used to communicate nociceptive information.
- Nerve endings may contain stretch sensitive Na+ channels;
- Upon stretch, channels open which generates action potential;
- Afferent sensory information.

Question 5

Afferent Pain Pathways

Answer 5

Different types of fibers communicate information differently.

C Fibers
Ab, Ad Fibers
Aa Fibers

Question 6

C Fibers

Answer 6

• Small, unmyelinated; - Nociceptive.

- Aching, throbbing; - Not localized.

Question 7

Ab, Ad Fibers

Answer 7

• Medium, myelinated;
• Nociceptive & non-nociceptive.
• Sharp pain;
• Localized
• Withdraw suddenly.

Question 8

Aa Fibers

Answer 8

• Large, myelinated;

- Light touch, proprioception.

Question 9

Different Types of Pain

Answer 9

Somatic Pain

Visceral Pain

Question 10

Visceral Pain

Answer 10

• Results from the activation of nociceptors of the thoracic, pelvic, or abdominal viscera;
• Poorly localized;
• Nociceptors sensitive to distention (stretch), ischemia and
  inflammation;
• Not cutting or burning;
• Slow pain only (C fibers)

Question 11

Somatic Pain

Answer 11

• Injury to skin, muscles, bone, joints, and connective tissues;
• Very localized;
• Nociceptors are sensitive to temperature, chemical irritants,
  mechanical stresses (cutting, burning);
• Both fast and slow pain (A and C fibers)

Question 12

Responding to Pain

Answer 12

Anterior Horn
Sensory Homunculus

Limbic System (arrow) emotional arousal
Midbrain (arrow) autonomic activation - Increased HR, BP

Question 13

Anterior Horn

Answer 13

• Site where pain is modulated;

- Afferent fibers sent to thalamus.

Question 14

Sensory Homunculus

Answer 14

• Somatosensory cortex;

- Where we consciously perceive localized pain.

Question 15

Endogenous Pain Modulation

Answer 15

Organisms need to be able to overcome pain.
Gating is one way in which humans modulate pain.
The gate theory of pain suggests that non- painful stimuli close the “gates” to painful input which prevents pain sensation from traveling to the brain.
- Shaking your hand after you hit it with hammer;
- Pain becomes less intense, you feel less pain;
- This is not an illusion, it has a biochemical process.

Question 16

Endogenous Pain Modulation

Answer 16

There are several ways to end (or modulate) pain signals.
Competing non-painful stimulus coming to same projection neuron;
- May inhibit or change firing rate of projection neuron.
- Competing inputs at the level of the projection neuron will blunt the signals being sent by C fibers (nociceptive).
Non-painful input closes the “gates” to painful input, which prevents pain sensation from traveling to CNS
- Stimulation by non-noxious input suppresses pain.

Question 17

Descending Pain Pathways

Answer 17

When painful stimulus come in from the periphery, it wants to activate neurons in the spinothalamic tract.
In response to this noxious stimulus, the brain will activate
descending neural pathways to dampen afferent signaling.
- 5-HTandNEcausethereleaseofcannabinoidsandopioids which inhibit firing of afferent neurons in spinothalamic tract à signal doesn’t get through.
Midbrain
- Releases dopamine & norepinephrine;
Raphe Nucleus
- Releases 5-HT;
Both are capable of inhibiting afferent signaling pathway through the spinothalamic tract.

Question 18

Chronic Pain - Inflammation

Answer 18

You need an ongoing signal to persist in order to tell you to rest your body (e.g. site of tissue damage).
Inflammation is the bridge from acute painful stimulus to chronic.
Inflammation is a localized physical condition in which part of the body becomes reddened, swollen, hot, and often painful, especially as a reaction to injury or infection.
Pro-inflammatory cytokines are released;
Makes peripheral nerves more excitable;
Makes dorsal horn more excitable;
Makes thalamus and somatosensory cortex more excitable.

These are the ongoing upregulated pain processes that are regulated in states of chronic pain.

Question 19

Chronic Pain - Sensitization

Answer 19

There are several mechanisms by which pain signals are upregulated in cases of chronic pain:

• Increase # of glutamate (excitatory) receptors;
• Post-synaptic membranes is hyperexcitable;
• Even normal stimulus will come through nerve, but is perceived as noxious.

Broken/damaged cells release pro-inflammatory cytokines (e.g. prostaglandin, bradykinins).
- Prostaglandin and bradykinin upregulate receptors on neve terminals;
- Leads to hyperexcitability à CNS sensitization;
- Also attracts neutrophils, causes blood vessels to swell,
area gets red, etc.
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin;
- Stops/interrupts inflammatory cascade

Question 20

Chronic Pain - Sensitization

Answer 20

Allodynia

Hyperalgesia

Question 21

Hyperalgesia

Answer 21

Stimulus that should be a little bit painful is very painful;

• Pain is out of proportion with stimulus;
• Hyperactivation of peripheral nerve fibersàC-fiber overactivity.

Question 22

Allodynia

Answer 22

• Stimulus that should not be painful is painful;

- A-fiber mediated.

Question 23

Neuropathic Pain

Answer 23

Neuropathic pain is the generation of painful signals due to damage to the central (or peripheral) nervous system.
Typically caused by upregulated or dysfunctional ion channels (e.g. sodium channels);
- Can occur on damaged nerves or nearby undamaged nerves;
- Leads to hyperexcitability;
- Painful signals in the absence of any tissue injury.

Question 24

Pain Management

Answer 24

Pharmacological pain management

• —Locally acting agents:
• Local anesthetics (e.g. lidocaine)
• Topical NSAIDs
• —Non-opiates
• COX inhibitors (e.g. ibuprofen, naproxen)
• Acetaminophen
• Neuropathic agents (e.g. gabapentin)
• Cannabinoids
• Antidepressants (e.g. SSRI, TCAs)
• —Opiates
• Codeine
• Morphine
• Hydromorphone Fentanyl
• Methadone

Question 25

Non-pharmacological pain management

Answer 25

Local
- Fixation of tissue;
- Surgical excision of mass; - Physiotherapy/massage;
- Compresses (hot, cold);
- Exercise.
Central
- Psychosocial/spiritual support;
- Stress management;
- Distraction;
- Deep brain stimulation; Exercise, physiotherapy.