Lecture 5.1 The Neural Basis of Pain and Analgesia Flashcards
What is Nociception?
Non-conscious neural traffic in response to (potential) trauma
What is Pain?
Complex and unpleasant awareness of a sensation
What Factors influence Pain? (7)
- Experience
- Expectation
- Context
- Culture
- Mood
- Cognitive Set
- Injury
What is IASP definition of Pain?
An unpleasant sensory and emotional experience associated with actual or potential tissue damage
What is the link between pain and nociception?
- Nociception leads to pain
- But pain isn’t only nociception
What is the Neural basis of Pain?
- Unclear
What parts of the brain are though to be involved in the Neural basis of Pain? (5)
- Ascending & Descending Pathways
- Somatosensory Cortex – perception of pain
- Amygdala – fear
- Hippocampus – memories
- Prefrontal Cortex – planning and reaction
How do Pain Receptors (Nociceptors) work?
- Free nerve endings sensitive to mechanical, thermal,
and/or chemical stimulation - Contain TRP channels (cation channels)
What can trigger TRP channels? (5)
- Inflammation
- Injury
- Nerve invasion e.g. cancer
- Injury to CNS
- Abnormal activity (eg chronic regonal pain syndrome)
What do the Spinothalamic Tracts detect? (3)
- Pain
- Temperature
- Crude Touch
- Carries information from the skin to the thalamus
where it is processed and transmitted to the primary
sensory cortex
What fibres is pain is transmitted via? (2)
and C Fibres
What is the structure and function of Aδ Fibres?
- Myelinated
- Transmit fast, sharp, well localised pain
What is the structure and function of C Fibres?
- Unmyelinated
- Transmit slow, diffuse, dull pain
What is Visceral/Organ Pain?
- It is diffused and poorly localised
- Organs have relatively few pain sensors
- Enter spinal cord at multiple levels
- No cortical mapping
- Referred pain
Modulation of Pain: Spinal Cord (1)
Gate Theory of Pain
Modulation of Pain: Central (2)
- Endogenous neuromodulatory systems (opioids,
endocannabinoids) in brain and spinal cord - Central modulation/descending signals from the brain
What is the Gate Theory of Pain?
- Modulation of nociception at the spinal level in the
substantia gelatinosa of the dorsal horn - Rubbing a painful area reduces the sensation of pain =
Gate Theory - The touch pathway neurons– activate an inhibitory
neuron reducing ascending pain signals
What does PAG stand for?
Periaqueductal Grey
What does RVM stand for?
Rostroventromedial Medulla
Central Modulation of Pain
Descending analgesia producing pathways descend from the brain stem to the spinal cord
What is Chronic Pain?
Any pain that lasts for more that 3 months past the normal healing time for an injury or disease
What is Hyperalgesia?
A stimulus that would normally be perceived as slightly painful is perceived as significantly more so
What does increased excitability of neurones in the dorsal horn of the spinal cord lead to?
It leads to allodynia, perception of pain from something that is normally an innocuous stimulus
What is Neuropathic Pain?
Pain caused by a lesion or disease of the somatosensory nervous system
What can cause Neuropathic Pain? (6)
- Cancer
- Post Herpetic Neuralgia
- Phantom Limb
- Diabetes
- MS
- Spinal Injury
What can cause Neuropathic Pain on a Thalamic/Cortical Level? (3)
- Infarctions
- Tumours
- Multiple Sclerosis
What can cause Neuropathic Pain on a Brainstem Level? (3)
- Infarctions (Wallenberg’s Syndrome),
- Tumours
- Multiple Sclerosis
What can cause Neuropathic Pain on a Spinal Level? (2)
- Spinal Cord Injuries
- Multiple Sclerosis
What can cause Neuropathic Pain on a Peripheral Level? (5)
- Diabetic Neuropathies
- Peripheral Trauma
- Plexus Avulsion
- Dorsal Rhizotomy
- Herpes Zoster
After a peripheral nerve injury sensitisation occurs it can lead to….? (7)
- Decreased threshold of the nociceptor to activation
- Increased receptive field of nociceptors
- Allodynia
- Hyperalgesia
- Hyperpathia
- Emergence of spontaneous activity / increased
excitability - Damaged peripheral nerves develop abnormal sodium
channels which fire dysfunctionally and demonstrate
different depolarisation properties
What is Hyperpathia?
Prolonged post stimulus sensations
Symptoms of Neuropathic Pain (3)
- Shooting and Burning Sensation
- Tingling and Numbness
- Unpredictable
Treatment of Neuropathic Pain (4)
Offer a choice of amitriptyline, duloxetine, gabapentin or pregabalin as initial treatment for neuropathic pain
Types of Analgesia (5)
- Paracetamol
- NSAIDS
- Opioids
- Adjuvants
- Placebo
WHO Analgesic Ladder (3)
- Step 1: Non-Opioids
- Step 2: Weak Opioids
- Step 3: Strong Opioids
- Ajduvants
Examples of Non-Opioids (2)
- Paracetamol
- NSAIDs – ibuprofen, diclofenac, naproxen
Examples of Weak Opioids (2)
- Codeine
- Tramadol
Examples of Strong Opioids (4)
- Morphine
- Diamorphine
- Fentanyl
- Alfentanyl
Examples of Adjuvants (9)
- Antidepressants
- Anticonvulsants
- Antispasmodics
- Steroids
- Muscle Relaxants
- Local Anaesthetics
- Bisphosphonates
- Radiotherapy
- Nitrous Oxide
Non-Pharmacological ways to manage Pain (6)
- TENS
- CBT
- Meditation
- Acupuncture
- Massage
- Hypnosis
What Opioid Receptors are there? (3)
- µ (mu)
- δ (delta)
- ƙ (kappa)
What Opioid Receptors is Codeine an agonist to?
Partial/weak (µ) mu-opioid receptor agonist
What Opioid Receptors is Morphine an agonist to?
Full agonist at mu-opioid receptors in the CNS
How does Morphine work?
- Bind receptors in regions of the CNS involved in
transmission and modulation of pain - Dampen nerve signals transmitting pain
Side-Effects of Opioid use (10)
- Euphoria
- Sedation
- Respiratory Depression
- Tolerance
- Miosis
- Nausea & Vomiting
- Cough Suppression
- Constipation
- Dependence
- Addiction
How do Cannabinoids work?
- Cannabinoids inhibit excitatory synaptic transmission
in substantia gelatinosa cells - Cannabinoid (CB1) receptors are expressed
presynaptically, where they inhibit transmitter release
from nociceptive primary sensory neurones - Cannabinoids act to reduce experimental models of
pain – non-opiate based analgesia
How is Acupuncture theorised to work?
- Acupuncture involves the insertion of extremely fine
needles into the skin at specific acupoints - This may relieve pain by releasing endorphins, the
body’s natural pain-killing chemicals - They also affect the part of the brain that governs
serotonin, a brain chemical involved with mood
