Week 6 Lesson 42: Sense of Pain

What is an unpleasant sensory and emotional experience associated with associated with actual or potential tissue damage?

Pain

What is the purpose of pain?

Protection from a harmful event + Protection from further damage during healing

Where are peripheral pain-sensitive neurons with receptors located?

In their free nerve endings

What peripheral pain sensitive neurons are most numerous in the skin and read what type of pain?

Somatic superficial pain

What peripheral pain sensitive neurons are less numerous in the deeper and read what type of pain?

somatic deep pain

What peripheral pain sensitive neurons are the least numerous in the viscera and read what type of pain?

Visceral pain

Are their pain sensitive neurons with receptors in the brain?

None in the brain tissue itself

Pain-sensitive free nerve endings can contain what three types of nociceptors?

1. Mechano-nociceptors

2. Chemo-nociceptors

3. Thermo-nicoceptors

What nociceptor responds to strong pressure, stretch and tissue disruption?

Mechano-nociceptors

What nociceptors are the most common type and respond to chemicals released during cell injury and inflammation?

Chemo-nociceptors

What nociceptors respond to extreme cold or heat?

Thermo-nociceptors

What are the two types of neurons that carry nociceptive pain?

A-delta and C fibers

Which type nociceptive neuron reacts first, fast, and mostly to superficial pain?

A-delta neurons

What is the main neurotransmitter of A delta neurons?

Glutamate

What neurotransmitter is quickly released into synapses and quickly degraded, causing it to be fast and short-acting for A-Delta neurons?

Glutamate

What are the two receptors that glutamate bind to in the a delta neuron?

AMPA and NMDA receptors

What nociceptive neuron carry mostly mechano-nocicpetors and respond to the initial mechanical force of the injury of the body surface = superficial pain?

A-Delta neurons

What are the two events that A-Delta neurons are responsible for?

1. Pain reflex

2. Pain perception and response

What reflex is caused by the 1st order neurons synapse with lower motor neurons in the spine to instantly withdraw the affected limb?

Withdrawal reflex

Describe the 1st, 2nd, to 3rd neuron order pathway of the A-delta fibers?

1st order = A-Delta fibers to Dorsal horn and 2nd neuron

2nd order = 2nd order axons in lateral spinothalamic tracts to ARAS

3rd order = Project ARAS to the somatosensory cortex for acute pain perception and localization

What is important to remember about pain perception/pain transmission in animals vs humans?

Majority of 2nd order axon cross (70%), pain transmission occurs bilaterally in animals

What is the purpose of pain?

Enables the animal to instantly withdraw from the source of pain via an unconscious withdrawal reflex and concious withdrawal behavior

What nociceptive neuron is much more numerous than A-Delta in the deep skin and tissues, and is the second, slow response mostly to deep pain?

C Neurons

What is the main neurotransmitter in C-Neurons?

Substance P

What neurotransmitter is slowly released into synapses and slowly degraded making it longer acting system compared to glutamate?

Substance P

What neurotransmitter binds to neurokinin-1 NK1 receptors which is the major receptors in the entire pain processing system?

Substance P

What does it mean for C-fibers to be polymodal?

It has multiple receptors such as mechano, chemo, and thermo receptors

What nociceptive neuron responds most strongly to chemicals released during tissue injury with subsequent pro-inflammatory mediator release (Inflammatory soup)?

C-neurons

Describe the 1st, 2nd, and 3rd order pathways of C-neurons.

1st order = C-Neuron fibers enter through the dorsal horn to the 2nd order

2nd order = C-Neurons ascend bilaterally via several deep tracts called medial spinothalamic tracts to the ARAS.

3rd order = From the ARAS C-fibers are widely distributed within the brain

Where does the C-neurons distribute the pain signal within the brain?

1. Hypothalamus

2. Limbic system

3. Somatosensory cortex

What happens when the deep pain signal stimulates the hypothalamus?

Sympathetic response to pain such as increased HR, BP, RR, etc

How does the deep pain stimulate the limbic system?

Emotional response such as fear

Behavioral responses

Memory of pain

How does the deep pain stimulate the somatosensory cortex?

Few projections and a vague localization

How is deep pain percieved?

Dull, aching background, burnign pain (Deep aching pain)

How long does the second pain last?

As long as nociceptive pro-inflammatory chemicals are present

What is the purpose of deep pain?

In enables the animal to protect itself or damage body part while its healing and to avoid future exposure

Due to their locatio and multiple bilateral transmission pathways these nociceptive neurons are very resistant to injury?

C-Neurons

What kind of spinal cord injury must be theire to abolish deep pain sensation?

Severe and extensive spinal cord injuries

What type fo pain is a result from damage to nervous system itself, leading to spontaneous action potentials i the affected pain neurons causing ectopic firing?

Neuropathic pain

What type of pain is caused by nerve compression, external nerve injury, neurogenic infection, metabolic nerve damage and described as tingling, pins and needles?

Neuropathic pain

What are two examples of Neuropathic pain?

1. Phantom pain

2. Trigeminal-mediated head shaking syndrome

What neuropathic pain is experienced in a body part that is no longer their. The cut-off neurons can develop into hyperactive neuromas with spontaneous firing. Because of the point to point projection, pain is localizes to where the hyperactive neuron originally came from?

Phantom pain

What neuropathic pain is caused by facial pain caused by spontaneous firing of the Trigeminal nerve cause is unknown?

Trigeminal mediated head-shaking syndrome in horses

What spinal cord circuit has a dorsal horn transmission is under control of many inhibitoy interneurons?

Gate control mechanism

What are the two main neurotransmitters used in the gate control mechanism?

GABA and Glycin

The gate control circuits are used to manipulate pain, such as rubbing and touching a painful area, which reduces pain transmission, which is the principle for what treatment?

Counter irritation treatment

In the gate control mechanism, simultaneous pain and touch stimulation in the same area causes touch collateral stimulation of inhibitory interneurons, inhibiting what?

Inhibiting pain transmission form 1st to 2nd pain neurons causing the gates to close

What pathway originates in the midbrain, is activated by incoming pain and by stress. It descends in the spinal cord and ends in the dorsal horns. The neurotransmitters reduce or inhibit signal transmission from the 1st to 2nd order pain neurons.

Descending analgesia pathway

What are the three Neurotransmitters of the Analgesia pathway?

1. endogenous opioids

2. serotonin

3. norepinephrine

What are the three groups of endogenous opioids?

1. Endorphins

2. Encephalins

3. Dynorphins

What drugs are widespread within the central and peripheral nervous system and other tissues?

Endogenous opioids

Opioids induce what two perceptions on pain?

Hypoalgesia or complete analgesia

What are the effects of opioids when the are centrally released?

• reduced pain processing, stress, anxiety

• Increase relaxation, can induce euphoria

What inhibitory pain modulator is released at the dorsal horn level and activates inhibitory interneurons, causing an analgesic effect?

Seretonin

What inhibitory pain modulator is released at the dorsal horn level blocking the release of excitatory neurotransmitters causing an analgesic effect or is released in several brain areas upon pain stimuli causing sedation?

Norepinephrine

What pathway is also activated during intense exercise, extreme excitement, and during acupuncture?

The analgesia pathway

What sensitization mechanism involve the free nerve endings?

Peripheral sensitization

What sensitization mechanism has the pain synapses in the dorsal horns and brain?

Central sensitization

How does sensitization mechanisms effect the pain threshold?

lowers the pain threshold

What is the purpose of sensitization?

increase the protection of the injured area during healing

What form of sensitization is an exaggerated pain response to a noxious stimulus?

Hyperalgesia

What form of sensitization is a pain response to a non-noxious stimulus?

Allodynia

What type of sensitization involves only functional changes in neurons and is fully reversible as the injury heals, caused by continuous exposure to inflammatory mediators, and can develop within minutes or hours of the injury?

Physiological sensitization

Describe the mechanism of physiological sensitization.

1. Prolonged opening of nociceptor channels in the nerve ending

2. Prolonging the opening of synaptic channels in the dorsal horn and the brain

3. Prolonged opening of Ca channels causes an increased neurotransmitter release at synapses

4. Recruitment of silent nociceptors to transmit pain

What is the mechanism of healing during physiological sensitization?

As healing progresses → reduced inflammatory stimuli → regression of functional sensitization mechanism → return to normal pain thresholds

What type of sensitization involves structural change in the pain pathways and is mostly irreversible even after healing is completed, serving no purpose?

Pathological sensitization

What type of pain can exist in the absence of an adequate injury and can become a self-substaining process, predisposing the patient to chronic pain?

Pathological pain

What type of pain is defined as pain lasting more than 3-6 month?

Chronic pain

What type of pain can be caused by persistent inflammatory pain due to an ongoing disease?

Chronic pain

What is an example of something to cause chronic pain?

Osteoarthritis

What type of pain is often therapy-resistant and is key to prevent the development of this type of pain using pre-emptive multimodal analgesia?

Chronic pain

Unmanaged pain can become debilitating, causing multiple stress responses via heightening what?

Sympathetic outflow and cortisol release

When an animal shows a withdrawal reflex, its reflex arc is intact. What does this mean for the brain?

It does not require perception of the stimulus in the brain

When the animal shows a behavioral response during the withdrawal reflex. What does this mean for the brain?

It has felt the stimulus meaning the pathway to the brain is open