Nociceptive System

Question 1

What is pain?

Answer 1

• The International Association for the Study of Pain defines pain as an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage
• Protective mechanism of the body - activation of nociceptors results in protective reflexes
• Pain is the feeling, or the perception, of irritating, sore, stinging, aching, throbbing, miserable, or unbearable sensations arising from a part of the body.

Question 2

What is nociception?

Answer 2

Sensory process that provides signals that trigger pain

Question 3

What are the 2 classes of pain?

Answer 3

Fast pain
Slow pain

Question 4

Describe fast pain?

Answer 4

Fast pain
Felt 0.1 sec after stimulus
Pricking pain, acute pain, electric, sharp pain
• Not felt in most of visceral tissues
• Precisely localised to the stimulated area

Question 5

What is slow pain?

Answer 5

• Felt after 1 sec or more and then increases slowly over secs or minutes
• Chronic pain, aching pain, throbbing pain
• Can occur both in the skin and viscera
• Persists for a long time e.g. back pain, tumours, headaches etc

Question 6

Describe heat pain?

Answer 6

• Average person first begins to perceive heat pain when skin is heated above 45°C
• Corresponds to temperature at which tissues are destroyed
• Tissue damage from bacteria /viral infection, muscle spasm will also cause pain

Question 7

Describe the cause of tissue ischemia?

Answer 7

• Due to accumulation of large amounts of lactic acid
• Can also be caused by accumulated levels of bradykinin and proteolytic enzymes during metabolism

Question 8

Describe muscle spasm as a cause of pain?

Answer 8

• Common cause of pain
• Due to direct stimulation of nociceptors
• Also due to compression of blood vessels leading to ischaemia

Question 9

Describe chemical stimuli as a cause of pain?

Answer 9

Acidic gastric juice leaking through a rapture caused by gastric ulcer/duodenal ulcer

Question 10

Describe overdistension of hollow viscus as a cause of pain?

Answer 10

• Cause pain by overstretch of the tissue themselves
• Also by collapsing blood vessels that encircle viscus

Question 11

What is a headache?

Answer 11

• A type of referred pain to the surface originating from the cranium and nasal sinus
• Inflammation of meninges, low cerebral spinal fluid pressure, blood vessels, alcohol

Question 12

Describe the structure of nociceptors and how they are stimulated?

Answer 12

• Nociceptors are free sensory nerve endings of myelinated or unmyelinated fibres
• They are activated by stimuli that have the potential to cause tissue damage (noxious stimuli).
• They are notably absent in the brain itself, except for the meninges, and from bone tissues
• The membranes of nociceptors contain ion channels that are activated by these types of stimuli

Question 13

Describe the 2 types of nociceptive axons?

Answer 13

1. Myelinated A delta fibres
   2 - 5 um in diameter
   conduct impulses at a rate of 6 - 30 m/s
   Mediate sharp pain
2. the unmyelinated C fibres
   0.4 - 1.2 um in diameter
   conduct at 0.5 - 2 m/s
   mediate slow dull pain

Question 14

Describe the location and course of nociceptors?

Answer 14

• A and C afferent fibres synapse in spinal cord where glutamate and substance P are neurotransmitters, respectively
• The cell bodies of nociceptors are located in the dorsal root ganglia (DRG) for the body and the trigeminal ganglion for the face
• Both have a peripheral slow and central axonal branch that innervates
their target organ and the spinal cord, respectively

Question 15

Describe different types of nociceptors?

Answer 15

1. Mechanical nociceptors
   • Respond to strong pressure (from sharp objects)
2. Thermal nociceptors
   • signal burning heat (245°C) or cold
3. Chemical nociceptors
   • respond to a variety of chemical stimuli eg K*, bradykinin, extremes of pH, neuroactive substances e.g. histamine, serotonin, proteolytic enzymes
   • stimulate slow pain

Question 16

What hyperalgesia?

Answer 16

• Increased sensitiveness to noxious stimuli by damaged tissue
- skin, joints, or muscles that have already been damaged or inflamed are unusually sensitive
• Hyperalgesia can be:
1. a reduced threshold for pain
2. an increased intensity of painful stimuli
3. even spontaneous pain

Question 17

Describe primary and secondary hyperalgesia?

Answer 17

• Primary hyperalgesia: occurs within the damaged tissue
• Secondary hyperalgesia: within 20 minutes of injury, tissues surrounding the damaged area may become supersensitive.

Question 18

Describe the pathophysiology of hyperalgesia?

Answer 18

• Damaged tissue releases variety of chemical substances (inflammatory soup) from itself, blood and nerve endings eg., K, H, bradykinin, prostaglandin, serotonin, that activate nociceptors
• Blood vessels become leaky, and cause oedema and redness
• Mast cells release histamine which excites nociceptors
• Substance P is
synthesized by nociceptors
• Activation of one branch of a nociceptor axon can lead to the secretion of substance P by the other branches of that axon in the neighbouring skin
• Substance P causes vasodilation and the release of histamine from mast cells.
• Bradykinin directly depolarizes nociceptors and stimulates long-lasting intracellular changes that make heat-activated ion channels more sensitive
• Prostaglandins do not elicit overt pain but increase greatly the sensitivity of nociceptors to other stimuli.

Question 19

What is allodynia?

Answer 19

• Allodynia is defined as “pain due to a stimulus that does not normally provoke pain.”
• An example would be a light feather touch (that should only produce sensation), causing pain.
• Allodynia is different from hyperalgesia, which is an exaggerated response from a usually painful stimulus, although both can and often do co-exist.

Question 20

What are pain pathways?

Answer 20

• Sensations of pain are transmitted into the spinal cord where they synapse with 2nd-order neurons in the dorsal horn of spinal cord or interneurons for local circuit
• 2nd-order neurones ascend to the brain via the spinothalamic tracts
• These synapse with 3rd-order neurons in the thalamus, which proceed to the postcentral gyrus
• Branches of pain pathways also terminate in the limbic system and hypothalamus

Question 21

Describe the analgesia system in the CNS?

Answer 21

• (1) The periaqueductal gray
(PAG) and periventricular areas of the mesencephalon and upper pons surround the aqueduct of Sylvius and portions of the third and fourth ventricles.
• Neurons from these areas send signals to (2) the raphe magnus nucleus, a thin midline nucleus located in the lower pons and upper medulla, and the nucleus reticularis paragigantocellularis, located laterally in the medulla.
• From these nuclei, second-order signals are transmitted down the dorsolateral columns in the spinal cord to
(3) a pain inhibitory complex located in the dorsal horns of the spinal cord.
• At this point, the analgesia signals can block the pain before it is relayed to the brain.

Question 22

What is referred pain?

Answer 22

• Pain that is perceived as coming from an area that is remote from its actual origin
• Several neuroanatomic and physiologic theories state that nociceptive dorsal horn and brain stem neurons receive convergent inputs from various tissues.
• As a result, higher centres cannot correctly identify the actual input source

Question 23

Describe examples of referred pain?

Answer 23

• Pain that originates in the viscera but felt in the somatic structure, a distance away eg. Angina pectoris
• pain originates in the myocardium, but felt in the inner aspect of left
arm.
• Pain in the shoulder tip caused by irritation of the central portion of diaphragm
• Pain in the testicle due to the distension of ureter

Question 24

What is visceral pain?

Answer 24

Visceral pain
• Pain arising from internal body organs
• Referred pain
Poorly localised and diffuse
• Dull, aching, cramping, waxing-and-waning

Question 25

Describe the clinical presentation of visceral pain?

Answer 25

Often associated with marked autonomic phenomena (sweating, nausea, hyperventilating etc)
• Strong emotional responses (fear, distress, crying, vocalising, rolling-around)
• angor animi: a strong sense of doom & panic, going to die
• e.g. period pain, heart attack, kidney stones, labour pain

Question 26

What is neuropathic pain?

Answer 26

• Pain caused by damage or disease affecting the somatosensory nervous system
• Approximately 15-25% of chronic pain is neuropathic, with the most common conditions including diabetic neuropathy, postherpetic neuralgia, and radiculopathy.
E.g. Phantom limb pain
• ongoing painful sensations that seem to be coming from the part of the limb that is no longer there

Question 27

Describe the pathophysiology of neuropathic pain?

Answer 27

1. Cellular response
   • Schwann cells respond to nerve damage by proliferating rapidly, cleaning up the dead tissue and laying groundwork for axonal regeneration
   • Activated macrophages are recruited from blood to aid in the repair process soon thereafter.
2. Inflammatory mediators and receptors
   • Nerve damage and inflammation involves a myriad of mediators originating from inflammatory cells as well as nerve cells and Schwann cells
3. Ion channel expression
   • In neuropathy and pain, increased calcium and sodium flux across the membrane results in an altered excitation threshold that leads to abnormal action potential and continuous firing of the nerves
4. Metabolic Response
   Continuous neural activities as they occur in chronic pain as well as inflammatory processes are energy-demanding processes

Question 28

What is the gate theory of pain control?

Answer 28

• According to the gate theory of pain, inhibitory interneurons regulate the transmission of ascending nociceptive information at the level of the second order neuron, allowing modulation of the signal
• The ‘gate’ is the mechanism where pain signals can be let through the spinal cord or restricted.
If the gate is open, pain signals can pass through and will be sent to the brain to perceive the pain.
If the gate is closed, pain signals will be restricted from travelling up to the brain, and the sensation of pain won’t be perceived

Question 29

Describe the first component of the first gate theory of pain control?

Answer 29

• 1st component is localised in the spinal cord
• Consists of inhibitory neurons that link large diameter mechanoreceptor axons with small diameter nociceptive axons as they enter dorsal horn of spinal cord
• When the mechanoreceptor pathway is active, it causes interneurons to inhibit nearby nociceptive pathways suppressing painful info before it projects up the spinal cord

Question 30

Describe the second component of the gate theory of pain control?

Answer 30

• 2nd component localised in the periaqueductal gray (PAG) matter
• PAG receives emotional info from several brain areas and sends the same via descending pathways to the dorsal horn of spinal cord where they depress nociceptive
neurons
• Strong emotion, stress blunts pain perception
• Endorphin, serotonin,
enkephalins and serotonin are the neurotransmitters in this pathway

Question 31

Describe pain management?

Answer 31

1. Acetaminophen (Tylenol, Paracetamol)
   • first-line for mild/moderate pain
2. Non-steroidal anti-inflammatory drugs
   (NSAIDs) e.g. aspirin, spinothalamic ibuprofen
3. Opioid agonists e.g. heroin, codeine,
   morphine
4. Acupuncture
5. Psychoprophylaxis e.g breathing exercises during labour

Question 32

Describe herpes zoster (shingles)?

Answer 32

• Herpes LoSter (On y
.
Occasionally herpes virus infects a dorsal root ganglion, causing severe pain in the dermatomal segment subserved by the ganglion
• The virus is carried by neuronal cytoplasmic flow outward through the neuronal peripheral axons to their cutaneous origins, causing a rash that vesiculates crusts over

Question 33

Describe tic douloureux?

Answer 33

• Tic Douloureux
• Trigeminal neuralgia
• The pain feels like sudden electrical shocks, and it may appear for only a few seconds at a time or may be almost continuous

Question 34

Describe Brown-Sequard syndrome?

Answer 34

• Brown-Séquard Syndrome
• Occurs when the spinal cord is transected or only one side (hemisection)
The sensations of pain, heat, and cold by the spinothalamic pathway are lost on the opposite side of the body in all dermatomes two to six segments below the level of the transection
1. Level of the lesion
2. Ipsilateral loss of proprioception and vibratory sensation occurs below the level of the lesion (dorsal columns) and motor function (corticospinal tract).
3. Contralateral loss of pain and temperature sensation occurs beginning approximately 2 levels below the level of the lesion (spinothalamic tract).

Question 35

Describe the pathways to proprioceotion?

Answer 35

1. Conscious proprioception travels in the DCML
   • deals with aspects such as
   Gracillis and judging the weight of an object or where a person’s limbs are in space.
2. Unconscious proprioception travels in the spinocerebellar tract and serves as an important backup to conscious proprioception involved in the acquisition and maintenance of complex, skilled movements such as walking, talking and writing.

Question 36

What is interception?

Answer 36

The perception of sensations from inside the body
E.g. heart beat, respiration, satiety as well as the ANS activity related to emotions

Question 37

Interception encompasses?

Answer 37

• (1) the afferent (body-to-brain) signalling through distinct neural and humoral (including immune and endocrine) channels
• (2) the neural encoding, representation, and integration of this information concerning internal bodily state
(3) the influence of such information on other perceptions, cognitions, and behaviours
• (4) and the psychological expression of these representations as consciously accessible physical sensations and feeling
• Helps maintain homeostasis and interpret physical sensations to guide health-related behaviour

Question 38

Describe thermoreception?

Answer 38

• Temperature-sensitive neurons clustered in the hypothalamus and the spinal cord are important in the
physiological responses that maintain stable body temperature
• However, it is the thermoreceptors in the skin that contribute to our perception of temperature
• Temperature sensitivity is not spread uniformly across the skin

Question 39

Describe the receptors of thermoreception?

Answer 39

• There are six distinct transient receptor potential (TRP) channels in thermoreceptors that confer different temperature sensitivities
• As a rule, each
thermoreceptive neuron appears to express only a single type of channel
• explains how different regions
Channel activity
of skin can show distinctly different sensitivities to temperature.
Come re rotors outnumber warm receptors by a ratio of 4:1

Question 40

How do thernoreceptirs work?

Answer 40

• As with mechanoreceptors, the responses of thermoreceptors adapt during long-duration stimuli
• For both cold and warm sensations, the range of temperatures between 29 and 37 °C is an adaptation zone.
• Application of an experimental stimulus or natural object within the adaptation zone to skin or mucosa is initially felt as warm or cold, but becomes neutral within minutes
• Temperatures above 45 °C
and below 15 °C are generally considered to be painful.
• Note that temperatures above
50 °C and below 0 °C can cause significant tissue damage.

Question 41

Describe thermoreception pathways?

Answer 41

• Carried in the lateral spinothalamic tract
• “Pa-Te-La” (Pain, Temperature via Lateral spinothalamic).
• Any stimulus that is too intense can be perceived as pain because temperature sensations are conducted along the same pathways that carry pain sensations