1.18 - Biological Basis Of Pain

Question 1

What is pain?

Answer 1

Pain is not a sensation (like vision/taste/touch etc), it is an unpleasant sensory and emotional experience (similar to hunger and thirst). It involves:
- Sensory components (pain feels “hot, sharp, dull, aching”)
- Emotional components (pain is distressing and or exhausting)
The perception of pain is a function of the brain’s processing of sensory input
Pain motivates a change in behaviour.

Question 2

What is nociception?

Answer 2

Nociception is the sensory process that carries signals that mediate the pain experience

Question 3

Describe the differences between acute and chronic pain

Answer 3

o Acute (short lasting) pain is beneficial. It results in response to injury or is a protective warning against harm, and is an important part of physiology and survival. Pain is a signal that aims to alter your behaviour to remove yourself from potential danger

o Chronic (long lasting pain) we generally don’t need. It is usually brought on by a pathophysiological state

Question 4

Describe the non-nociceptive innervation of the skin

Answer 4

Low threshold mechanoreceptors respond to tactile stimuli, and have two basic types of responses when their receptive fields (RFs) are stimulated:
o Fast adapting (FA1: superficial; FA2: deep)
o Slow-adapting (SA1: superficial; SA2: deep)

Increased stimulation frequency of SA –> Increased sensation of pressure(merkel; SA1)
Increased stimulation of FA –> tapping –> vibration –> texture

Increased stimulation frequency is not perceived as painful –> Pain and touch use separate pathways

Question 5

Which of the four groups of primary afferent axons are nociceptive?

Answer 5

A delta and C fibres (C are unmyelinated)

Question 6

What are the different types of nociceptors?

Answer 6

Mechanical
Thermal
Chemical
C-polymodal
Mechano-heat insensitive

Question 7

Describe Mechanical Nociceptors

Answer 7

selective for strong stimuli such as pinch and/or sharp objects that penetrate, squeeze or pinch the skin
o Sharp or pricking pain, via Aδ fibres
o Mediated by a mechanical deformation of the nociceptor membrane –> depolarisation

Question 8

Descrive Thermal Nociceptors

Answer 8

Thermal nociceptors: selective for noxious heat (temp. above 45oC), noxious cold (temp. below 5oC)
o Hot pain, via Aδ fibres (faster –> more appropriate for the withdrawal reflex)

Question 9

Descrive Chemical Nociceptors

Answer 9

selective for chemical irritants such as histamine, capsaicin, mustard oil and acids
Itch and irritation via non-myelinated C fibres

Question 10

Describe C-polymodal Nociceptors

Answer 10

Most common (nearly 50% of C-fibres), activated by noxious mechanical stimuli, noxious heat, noxious cold, irritant chemicals
o Slow dull burning pain or aching pain, via non-myelinated C fibres
o Perception persists long after the stimulus is removed

Question 11

Describe Mechanoheat insensitive Nociceptors

Answer 11

A C-fibre insensitive to noxious stimuli until sensitised

Question 12

Compare the paths of tactile and pain afferents in the spinal cord

Answer 12

Tactile afferents: Afferents carrying fine touch, vibration and proprioception etc. enter the dorsal horn and ascend in the dorsal columns and terminate in the dorsal column nuclei then relay to the thalamus. Their collateral inputs synapse deep in the dorsal horn

• Pain afferents: Pain and temperature afferents enter the dorsal horn and spread over up to 5 segments of the spinal cord in the zone of Lissauer. They make synapses in the substantia gelatinosa (superficial dorsal horn), and cross to the contralateral side where they enter the spinothalamic tract and ascend to the thalamus and/or other CNS targets

Question 13

What are the four important pain pathways?

Answer 13

Spino-spinal (withdrawal reflex)
Spino-thalamic
Spino-mesencephalic
Spino-reticular

Question 14

Describe the spin-reticular tract

Answer 14

Responsible for arousal –> to alert the CNS there is a painful event
The reticular formation projects to the thalamus, then to wide range of CNS regions

Question 15

Describe the Spinothalamic tract

Describe what it is responsible for, the inputs involved, the neurotransmitters used, the inhibition of the tract, its targets and final destinations in the cortex

Answer 15

Considered the most important pathway for somatic pain and thermal sensation
Responsible for: Pain location, intensity, sensory quality and emotional component

Inputs
Excitatory form cutaneous nociceptors
Excitatory from noxious stimulation of muscles, joints and viscera

Neurotransmitters
Released by nociceptive afferents activating spinothalamic tract cells include:
EAAs: Glutamate
Several peptides, including substance P (SP): produces longer lasting effects of glutamate; Calcitonin gene-related protein (CGRP): increased effect of SP by inhibiting its degradation
Cells inhibited by GABA, glycine and monoamines

Inhibtion
Large inhibitory RFs (may explain transcutaneous electrical stimulation and acupuncture), and can result from weak mechanical stimuli (e.g. rubbing)

Targets:
Thalamus (central lateral and ventral
posterior lateral nuclei)

Final Destination in the Cortex:
Conscious component of pain (and temperature), the perception of pain and memory of unpleasant experience
 - Somatosensory cortex
 - Cingulate gyrus
 - Insula cortex

Question 16

Describe the Spinomesencephalic Tract

Answer 16

Swearing and anger after pain (such as a cut) is mediated by this pathway
• Spinal projections to a variety of regions in the midbrain
• Responsible for the coordination of behavioural, emotional and autonomic components, as well as pain modulation to a noxious stimuli
• The periaqueductal grey (PAG) is an important component in this pathway for coordinating behavioural and motivational responses (e.g. vocalization and aversive behaviour)
- The PAG projects to the amygdala which provides a pathway for emotional responses to pain
- PAG projects to the hypothalamus orchestrating appropriate autonomic responses (e.g. increased heat rate for sharp pain, and decreased heart rate for deep pain)
- Projections to medullary raphe for analgesia

Question 17

Describe pain modulation. Where it can occur and what mechanisms do so

Answer 17

Peripheral: sensitisation of nociceptors
Spinal cord: Gate theory
Descending modulation: PAG-raphe-spinal pathway for analgesia

Question 18

Describe Afferent Pain regulation

Answer 18

Nociceptor sensitisation can results in hyperalgesia.
The gate theory control of pain is a spinal cord
mechanisms which explains how the activation of non-nociceptive inputs can mask pain:
o Stimulation of Aα and Aβ fibres:
- Excite inhibitory neurons
- Release of GABA
- Inhibit spinothalamic tract neurons
The interneuron plays a gating role

Question 19

Describe Descending Pain Regulation

Answer 19

The PAG sends descending projections to the raphespinal neurons in the nucleus raphe magnus
These cells inhibit spinothalamic tract neurons in the dorsal horn
They have a profound analgesic effect, and is thought to explain why soldiers at war or athletes can sustain horrific injuries during times of need.

Question 20

Describe Endogenous Opioid Mediated Analgesia

Answer 20

Endogenous opioid peptides play a key role in
centrally mediated analgesia. Endogenous opioids have a variety of roles in the CNS, not just related to analgesia
o Enkephalin
o Dynorphin
o beta- endorphin

Enkephalin may act
o Presynaptically to reduce the release of Substance P
o Postsynaptically by producing an IPSP

The endogenous analgesic effects of encephalin is blocked by naloxone, an opioid antagonist

Question 21

Describe the difference between neuropathic and neurogenic pain

Answer 21

Neuropathic pain is used to describe pain that occurs in the absence of nociceptor stimulation. Phantom limb pain is an example of neuropathic pain which can result from amputation. Neuropathic because there is no nociception from the missing limb to the brain but still receiving pain the “limb”
Neurogenic pain occurs due to primary damage of the nervous system (usually peripheral). Carpel tunnel is an example of neurogenic pain, where the median nerve is impinged by the carpel tunnel in the wrist

Question 22

Describe Neurogeninc and Neuropathic chronic pain

Answer 22

Neurogenic chronic pain arises from constant activation of nociceptors or their fibres
o Examples: arthritis, nerve entrapment, bulging disc,
temperomandibular disorder etc…
o No pain is felt after knee or hip replacement in rheumatoid patients as the pain causing signal is removed

Neuropathic chronic pain arises from central nervous system damage or changes (re-wiring)
o Examples: post-stroke pain, phantom limb pain, lower back pain, trigeminal neuralgia
o Does not require the periphery, e.g. thalamic stroke results in chronic pain without problems in lower pathway
o Anti-depressants can be effective against this type of pain but analgesics aren’t.