Lesson 42 - Nociception

1. lapses in house training

2. self-mutilation

3. enlarged pupils

4. acts out of character

5. grimaces

6. hunched

Which of the following are signs that your pet is in pain?

absence or relief of pain

What is analgesia?

pain caused by a stimulus that would not normally provoke pain

What is allodynia?

increased sensitivity to pain or a heightened response to painful stimuli

What is hyperalgesia?

neural process of encoding and processing harmful stimuli, leading to the sensation of pain

What is nociception?

specialized sensory receptors that detect harmful stimuli and send pain signals to the brain

What is nociceptors?

pain that originates from internal organs

What is visceral pain?

pain originating from the skin, bones, or joints

What is somatic pain?

chronic pain

What type of pain continues after the initial injury has healed?

minimum intensity of a stimulus that is perceived as painful

What is the pain threshold?

endorphins

What are naturally occurring chemicals in the brain that help to reduce pain and improve mood by acting as natural painkillers?

1. abnormal sensations in the skin which can sometimes be painful

2. tingling

3. itching

4. pins and needles feeling

What is parathesia?

phenomenon where repeated, low-level pain stimuli can lead to an exaggerated response, due to the CNS becoming sensitized

What is wind-up?

1. protection from a harmful event

2. protection from further damage during healing

What is the purpose of pain?

peripheral neurons with receptors in free nerve endings

What are the first order neurons for nociception like?

skin for somatic superficial pain

Where are first order nociception neurons most numerous?

1. deeper tissues for somatic deep pain

2. viscera for visceral pain

Where are there few first order nociception neurons?

in the brain tissue itself

Where are there no first order nociception neurons?

meninges and blood vessels

If someone is experiencing pain in their skull, what structures are most likely stimulating the nociception neurons?

1. mechano-nociceptors

2. chemo-nociceptors

3. thermo-nociceptors

What are the types of nociceptors?

strong pressure, stretch and tissue disruption

What do the mechano-nociceptors respond to?

chemical released during cell injury and inflammation

What do the chemo-nociceptors respond to?

chemo-nociceptors

What type of nociceptor is most common?

1. ATP

2. H

3. K

4. bradykinin

What are the chemicals released from cell injury that stimulate chemo-nociceptors?

1. pro-inflammatory cytokines

2. prostaglandins

3. TNF

4. NGFs

What are the chemicals released during inflammation that stimulate chemo-nociceptors?

1. A-delta neurons

2. C-neurons

What are the types of neurons that carry nociceptive pain?

1. small, myelinated axons

2. medium to fast transmission speed

3. carry mechano-nociceptors

4. few thermo-nociceptors

Which of the following are true about A-delta neurons?

glutamate

What is A-deltas main neurotransmitter?

quickly released and quickly degraded and binds to AMPA and NMDA receptors

What happens when glutamate is released from A-delta neurons?

initial mechanical force of the injury on the body surface

What do A-delta neurons respond to?

1. pain reflex

2. pain perception and response

3. synapse with lower motor neurons

4. synapse with second order sensory neurons

What are the two events that follow the arrival of A-delta signals in the dorsal horn?

first order A-delta neurons synapse with lower motor neurons to instantly withdraw the affected limb

What is the pain reflex?

withdrawal reflex

What reflex is a part of the pain reflex?

from painful location to synapse with second order sensory neurons in dorsal horn

What is the pain perception pathway for A-delta fibers?

travel from dorsal horn to spinothalamic tracts bilaterally to ARAS

What is the pain perception pathway for the second order sensory neurons?

from ARAS to the somatosensory cortex

What is the pain perception pathway for the third order sensory neurons?

spinothalamic tracts bilaterally in the spinal cord

What tracts does fast pain take to reach the cortex?

voluntary withdrawal behavior

What is the result of the first/fast pain response from the cortex?

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

What is the purpose of the first pain?

A-delta neurons

What neuron is involved in the first/fast pain pathway?

C-neurons

What neuron is involved in the second/slow pain pathway?

1. small, unmyelinated axons

2. slower transmission speed

3. more numerous than A-delta

4. carry mechano, chemo, and thermoreceptors

Which of the following is true about C-neurons?

Substance P

What is the main neurotransmitter for C-neurons?

slowly released and slowly degraded and binds to Neurokinin-1 receptors

What happens to substance P when it is released from C-neurons?

neurokinin-1 receptors

What are the major receptors in the entire pain processing system?

most strongly to chemicals released during tissue injury with subsequent pro-inflammatory mediator release

What do C-neurons respond to?

describes the variety of pro-inflammatory mediators and chemicals released during tissue injury

What does the term inflammatory soup mean?

spinothalamic tracts

What tracts are involved with the C-fiber pain response?

1. somatosensory cortex

2. hypothalamus

3. limbic system/amygdala

What parts of the brain are involved with second/slow pain?

sympathetic responses such as increased heart rate, blood pressure, respiratory rate

What is the hypothalamic response to second pain?

1. emotional responses such as fear, depression, aggression

2. behavioral responses such as avoidance, hiding, defense

3. memory of pain and future avoidance

What is the limbic system response to second pain?

vague localization due to having few projections into it

What is the somatosensory cortex response to second pain?

dull, aching, background, burning, diffuse pain

How is second pain perceived as?

instant, sharp, stinging, localized pain

How is first pain perceived as?

as long as the pro-inflammatory chemicals are present

How long does second pain last?

enables the animal to protect itself or the damaged body part while it is healing, and to avoid future exposure

What is the purpose of second pain?

damage to the nervous system itself leading to spontaneous action potentials

What causes neuropathic pain?

1. nerve compression like IVDD

2. external nerve injury

3. neurogenic infection like herpes

4. metabolic nerve damage like diabetic neuropathy

What are some examples that could cause neuropathic pain?

tingling, burning, shooting, electrifying, stabbing pain

How is neuropathic pain perceived as?

neuropathic pain

What type of pain is phantom pain?

hyperactive neuromas at the amputation site and point-to-point projection causes the pain to be localized to where the neurons originally came from

What causes phantom pain?

pain originating in the thigh and can travel down the leg

What does IVDD causing sciatic nerve compression cause?

facial pain caused by spontaneous firing of the trigeminal nerve with unknown cause

What is trigeminal-mediated headshaking syndrome in horses?

avoid overstimulation of the brain at times to enable survival

What is the purpose of the body reducing pain signaling?

1. spinal cord circuits/gate control mechanism

2. descending analgesia pathway

What are the physiological pain controlling mechanisms?

dorsal horn with inhibitory interneurons acting as the gates

Where does the gate control mechanism for pain occur?

GABA and glycin

What are the neurotransmitters used for the gate control mechanism?

simultaneous pain and touch stimuli in the same area cause inhibitory interneurons to be activated which inhibits the pain transmission from 1st to 2nd order

What is the pathway to the gate control mechanism?

rubbing, touching, or licking a painful area reduces pain transmission

What is the principle of counter irritation treatments?

midbrain in the periaqueductal gray

Where does the descending analgesia pathway originate?

higher pain processing centers and stress

What activates the descending analgesia pathway?

travels down spinal cord and ends in dorsal horns where it reduces or inhibits signal transmission between first and second order pain neurons

What is the pathway of the descending analgesia pathway from the brain?

1. endogenous opioids

2. serotonin

3. norepinephrine

What are the neurotransmitters of the descending analgesia pathway?

1. endorphins

2. encephalins

3. dynorphins

What are the groups of endogenous opioids?

Mu receptors

What receptors do endorphins bind to?

delta receptors

What receptors do encephalins bind to?

kappa receptors

What receptors do dynorphins bind to?

1. hypoalgesia / analgesia

2. reduce pain processing, stress, anxiety

3. increase relaxation, feeling of pressure and euphoria

What is the function of opioids?

1. intense exercise

2. extreme excitement

3. acupuncture

What are other activities that activate the analgesia pathway?

widespread throughout the body especially in central nervous system

Where are opioids released?

dorsal horn

Where is serotonin released?

activates inhibitory interneurons which inhibits transmission from first to second order neurons

What is the function of serotonin?

dorsal horn and several brain areas upon pain stimulation

Where is norepinephrine released?

binds presynaptic alpha-2 receptors which blocks release of excitatory neurotransmitters causing analgesia

What is the function of the norepinephrine released at the dorsal horn level?

activates auto-inhibitory alpha-2 receptors which moderates emotional response to pain causing sedation

What is the function of the norepinephrine released in the brain?

structural changes in the pain pathway due to repetitive and strong pain signaling

What is neuromodulation?

nociceptive nerve endings, spinal cord, and brain synapses

What structures may undergo neuromodulation?

lowers pain threshold, making pain worse

What does neuromodulation do to pain?

1. it resolves as the injury heals

2. increases the protection of the injured area during healing

Why is sensitization/neuromodulation a physiologic mechanism?

1. allodynia

2. hyperalgesia

What are the forms of sensitization?

1. embedding of more nociceptors

2. prolonged opening of nociceptor channels

3. recruitment of silent nociceptors

What changes happen to peripheral free nociceptive endings with sensitization?

1. receptor upregulation of NMDA and NK-1

2. increased release of glutamate and substance P

3. glial cells activation

4. disinhibition of gate control circuits

What changes happen to central neurons with sensitization?

release of pro-inflammatory mediators leading to neuroinflammation

What does glial cell activation result in?

1. happens in absence of adequate tissue injury

2. happens beyond expected time of healing

What are the key characteristics of chronic pain?

1. nociceptive pain wit sustained inflammatory processes 2. neuropathic pain

What is chronic pain usually a consequence of?

its therapy-resistant so key is to prevent the development of chronic pain using pre-emptive multimodal analgesia

What is the key to treating chronic pain?

1. left hind limb ipsilateral tract

2. right hind limb contralateral tract

What tracts would be blocked with left side damage to the spinothalamic system at L1/L2?

1. tachycardia

2. hypertension

3. tachypnea

4. renal dysfunction

5. stress responses

6. heightened sympathetic outflow

What are the consequences of unmanaged pain?

observation

What is the key to knowing whether or not an animal is in pain?

sensory pathways are open and animal had perception of that sensation in the brain

You're performing a neurological exam and you use a superficial skin prick and the animal looks up at you, what does that tell you?