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What is the purpose of pain?

- Pain usually caused by stimuli that is damaging tissue or that will damage tissue if allowed to continue.
- Learned about withdrawal reflexes last year
- Some pain though is inescapable such as that caused by deep tissue damage. Animals (and people) tend to stay immobile, withdraw socially and stop eating until recover or….


What are the clinical types of pain?

- Nociceptive pains
- Inflammatory Pain (can be clumped with nociceptive pain)
- Neuropathic pains


Describe nociceptive pain

Results from direct activation of nociceptors
- No nervous system lesion


Describe neuropathic pain

Results from direct injury to nerves in the peripheral or central nervous system
- Problems in the nervous system itself (peripherally or centrally)
- Spontaneous pain can occur
- Also amplification can occur
- Diabetic neuropathy, herpes zoster, etc. are examples


Describe inflammatory pain

- Active inflammation
- Sensory amplification is present
- Pain can be evoked by low and high intesnsity stimuli
- This is called sensory amplification
- Peripheral amplification (periphery) and central amplification (in spinal cord) are possible


Describe nociceptors

- Receptor type – free nerve endings of primary sensory neurons with cell bodies in the dorsal root ganglia and the trigeminal ganglia.
- Location: mainly found in skin, joints and muscle
- Abdominal pain can be caused by problems in the abdominal wall or stimulation of parietal nociceptors in the peritoneal lining of the abdomen.


Describe "silent" nociceptors

“Silent nociceptors” which only respond after tissue damage (or sensitization) are found in the viscera and also in the skin.


What can result from pain?

Ischemia can result in pain via the stimulation of acid-sensitive primary sensory nociceptors to the vasculature.


Describe protein receptors for capsaicin

VR-1 receptors
- also responds to noxious heat stimuli
- responds to many stimuli


Describe the inflammatory response to tissue damage

Damaged tissue releases substances
a. Prostaglandins
b. Serotonin (5-HT) – released by platelets
c. Bradykinin
d. Protons, H+ ( change pH)
e. Potassium

Net result is that the peripheral terminal of a sensory neuron is responding to all the substances by starting an action potential that goes to terminals that can release substance P or CGRP

Substance P releases histamine (sensitization of the cell, dilates blood vessels)

CGRP (dilates blood vessels)

The neuron terminal becomes very sensitive to firing and therefore continues to release substance P and CGRP

Note that substance P is released both centrally and peripherally


Two types of axons carrying pain information

- C fibers (small, unmelinated
- A delta (lightly myelinated, a little bigger)


What do you need to know about the anterolateral system?

The nociception pain fibers DO cross in the spinal pain


Describe referred pain

- The basis for referred pain may be convergence of somatic and visceral pain fibers on the same second-order neurons in the dorsal horn of the spinal cord that project higher brain regions
- The periaqueductal gray (PAG) is a part of a descending pathway that includes serotonergic neurons in the nucleus raphé magnus and catecholaminergic neurons in the rostral ventromedial medulla to modulate pain transmission by inhibition of primary afferent transmission in the dorsal horn


Describe dermatones

Sensory dermatomes. Pain located in the pattern of a dermatome occurs with spinal nerve injury and is referred to as radiculopathy.


What is important about referred pain?

It is CLINICALLY important ***


Describe the experiment of abdominal distension and pain

Functional MRI of thalamus of monkeys subjected to noxious distension of the colon and rectum. Activity abolished by lesion of the dorsal columns at T10, but not by “sham” surgery.


Describe a spinal cord lesion for abdominal pain

Myelin-stained section of the thoracic spinal cord from a patient who underwent midline myelotomy for the treatment of colon cancer pain that was not controlled by analgesics.

After surgery patient experienced relief from pain for the remaining three months of his life.

Only makes sense for terminally-ill patients


Where does most pain travel to the brain?

MOST pain goes up anterolateral system

Remember, this crosses in the spinal cord


Describe the pathway of discriminative pain pathways

Discriminative pain pathway
- Cross in spinal cord
- Go up contralaterally
- Reach primary somatosensory cortex
- Face is a little different, but still winds up in the same place


Describe the nociceptive types of pain

Nociceptive or physiologic pain
- Fast pain from stimulating A delta fibers
- Slow/delayed pain from stimulating C fibers

Inflammatory Pain
- Physiologic pain that has been intensified by peripheral sensitization.

Central sensitization can also intensify physiologic pain.


What is the "wind up" phenomenon?

Central sensitization can intensify physiological pain.
- Central sensitization is “an immediate onset, activity-dependent increase in the excitability of neurons in the dorsal horn of the spinal cord following high levels of activity in the nociceptive afferents.”
- One type of central sensitization is “wind-up”, a “progressive increase in the discharge rate of dorsal horn neurons in response to repeated low-frequency activation of nociceptive afferents.”

Makes the cell more receptive to incoming pain signals


What is hyperalgesia?

- An increased response to a stimulus which is normally painful
- Hyperalgesia is due to both peripheral and central sensitization.


What is neuropathic pain?

- Results from direct injury to nerves in the peripheral or central nervous system
- Maladaptive in that it serves no known useful function


What can neuropathic pain cause?

Can cause allodynia – pain due to a stimulus which does not usually provoke pain


Describe allodynia

- Pain due to a stimulus which does not normally provoke pain ***
- IASP points out that term was originally introduced for ‘the conditions seen in patients with lesions of the nervous system where touch, light pressure, or moderate cold or warmth evoke pain when applied to apparently normal skin”
- IASP thinks that term is now appropriate any time a usually non-painful stimulus evokes pain.


What causes neuropathic pain?

Can be caused by both peripheral and central lesions
- Diabetic neuropathy
- Postherpetic neuralgia
- Phantom pain (can result from either peripheral or central nervous system lesion)


Describe the gate control theory

- Not necessary to know details of theory but basic ideas important.
- Stimulation of low threshold, large fiber A alpha and A-Beta mechanoreceptor afferents can inhibit the transmission of nociceptive input from A-Delta and C fiber afferents in the dorsal horn.


Give some examples of the gate control theory of pain

Common examples of application of idea related to theory:
- Reflexive shaking of the hand in response to a burn thus stimulating large fiber afferents that can attenuate the pain
- Rubbing your knee after banging it on a piece of furniture