Pain Pathway/physiology Flashcards
Define acute pain
Pain that occurs with acute tissue damage and subsides after tissue healing.
Define chronic pain
Pain that persists beyond the normal time of healing. Often cited as pain for >3 months.
What are nociceptors?
Free nerve endings of primary sensory (afferent) neurons.
What are the different types of nerve fibre involved in pain?
A-delta = acute pain (rapid, stabbing pain), myelinated
C-fibres = slower (0.5m/sec), higher activation thresholds (i.e. only higher temps elicit a response), non-myelinated. Repeated input from C-fibres contributes to central sensitisation in the dorsal horn.
What are A-beta nerve fibres?
Touch sensation rather than pain, myelinated
Which lamina in the dorsal horn do A-delta and C-fibres synapse at?
A-delta with lamina I & V
C-fibres with lamina II mostly
What is the route taken for afferent sensory neurons?
The first order nerve fibres synapse with the second order fibres within the lamina. The second order fibres travel up the spinal cord to the thalamus via the spinothalmic tract, where it then synapses with the third order fibre.
What are lamina?
Divisions or layer of the grey matter of the dorsal horn. Lamina I-VI
Define paresthesia and dysasthesia
An odd sensation and an unpleasant sensation
Define primary hyperalgesia
Exaggerated pain sensation to a painful stimulation. It occurs at the site of injury (peripheral sensitisation)
Define secondary hyperalgesia
It occurs in areas remote from the site of injury (central sensitisation) - lowered pain threshold. An example is reduced tolerance of having claws clipped on the hind limb with chronic hip arthritis.
Define allodynia
It describes altered perception where non painful stimuli are painful (like normal touch)
What is the spinothalmic tract?
It transmits nociceptive information from the dorsal horn of the spinal cord to the brain
What is the periaqueductal grey (PAG)?
A structure in the midbrain. Primarily responsible for descending modulation of pain perception
What is the Helsinki chronic pain index?
It is a pain scoring tool for dogs with chronic pain (particularly OA). Designed for owners to recognise and monitor pain.
How does central sensitisation happen with regards to NMDA receptors?
Glutamate usually acts on AMPA receptors, however…continued nociceptive stimulation within the spinal cord releases glutamate and substance P and removes the Mg2+ plug which usually blocks the N-methyl-d-aspartate (NMDA) receptor for glutamate, allowing priming of this receptor - leading to loss of neurons containing GABA (inhibition).
Examples of excitatory neurotransmitters
Glutamate, substance P and prostaglandins
Examples of inhibitory neurotransmitters
Serotonin, GABA, endorphins and noradrenaline
What is gate control theory?
It says that non-noxious tactile stimuli can cause modulation of nociceptive information in the spinal cord.
What is meant by the therapeutic index of a drug?
It is a ratio comparing the toxic dose with the therapeutic dose. The larger the TI (range), the safer the drug. Quantifies the safety of a drug.
What is the first pass effect?
Drugs given orally undergo some metabolism by the liver before entering systemic circulation
Where on the pain pathway does lidocaine act?
Lidocaine blocks voltage gated sodium channels in sensory neurons at the site of potential injury, preventing an action potential.
Systemically at low doses, it may block NMDA receptors.
AKA sodium channel blockers
Why can lidocaine not be given systemically to cats?
Lidocaine is cardio toxic in cats
How does ketamine prevent central sensitisation?
It blocks the excitatory effects of glutamate at NMDA receptors, preventing central sensitisation.
What drugs are known to help prevent central sensitisation?
Ketamine, methadone and amantadine
What is the mode of action of drugs like Gabapentin and Pregabalin?
They bind to alpha 2 delta -1 subunits (involved in regulating activity of voltage gated calcium channels) on the pre-synaptic membrane of neurons, decreasing the release of excitable neurotransmitters, thus preventing central sensitisation.
What is the mode of action of NSAIDs?
NSAIDs inhibit COX enzymes, blocking the conversion of arachidonic acid into prostaglandins (which are pro-inflammatory).
Inhibition of COX 1 enzymes are the ones that cause the ‘NSAID side effects’ gastric ulceration/renal failure.
COX 1 selective NSAIDs cause GI and renal side effects by blocking production of prostaglandins. How do the prostaglandins protect the stomach lining and kidneys?
Prostaglandins maintain renal blood flow and help regulate renal blood pressure. They also stimulate secretion of mucus and bicarbonate to protect the stomach lining and inhibit the secretion of gastric acid.
Do NSAIDs have any affect on neuropathic pain?
No, they do not.
What is the mode of action of alpha 2 agonists?
They inhibit noradrenaline release from afferent primary sensory neurons at the pre-synaptic membrane in the spinal cord, interrupting sympathetic activity.
Define nociception
The transduction, conduction, and CNS processing of nerve signals generated by stimulation of nociceptors. The physiologic process that leads to perception of pain.
Define anaesthesia
The following 5 components: Unconsciousness. Amnesia (loss of memory of pain or distress). Analgesia. Muscle relaxation. Diminished motor response to noxious stimuli. Reversibility
What are the five stages of the pain pathway?
Transduction, transmission, modulation, projection and perception
What is the substantia gelatinosa?
Generally referring to lamina II of the dorsal grey horn in the spinal cord
What is the Lissauer tract?
Primary sensory fibers carrying pain, temperature and touch information bifurcate upon entering the spinal cord. Their branches ascend and descend for several spinal segments in the dorsolateral
tract (Lissauer tract), before synapsing in the dorsal horn.
