Allodynia and Hyperalgesia

How does endogenous and pharmacological pain modulation therapy work?

* Opium poppy derivates have analgesic properties, and when injected into specific brain areas cause analgesia
* Endogenous opiod GPCRs and ligands discovered in pain pathway
* Electrical stimulation can reduce pain
* Blocked by opiate antagonist
* Morphine can reduce pain

Factors which contribute to pain perception

* Emotional context
* Attentional state
* Expectation
* Biological
* Genetic
* Environmental

Anxiety effect on pain

hyperalgesia - more pain

Placebo/nocebo effect on pain

* **Placebo** – positive expectation improves outcome
* **Nocebo** – negative expectation causes a negative effect (eg expectation of pain is fulfilled)

Primary vs secondary hyperalgesia

Primary hyperalgesia → At site of injury, occurs in damaged tissue

Secondary hyperalgesia → Occurs in undamaged surrounding tissue

Sensitised nociceptors exhibit…

* Lowered activation thresholds
* Increased responsiveness to noxious stimuli
* Spontaneous activity due to abnormal nerve changes

Allodynia

Pain evoked by stimuli which are not usually painful

* Eg - low intensity stimulus, unexpected painful response

Trigeminal neuralgia

* Example of…
* Caused by…
* Effects

* Demonstrates allodynia and hyperalgesia
* Caused by issue in skull
* Episodes of pain affecting one side of the face at a time

Peripheral sensitisation

Increased excitability of nociceptors following peripheral tissue injury or repeated noxious stimuli

Central sensitisation

Increased excitability in the CNS

Changes caused by nociceptors

Reduced threshold

Increased firing rate

Decreased threshold of activation = increased sensitivity/excitability of afferent following peripheral tissue injury/repeated noxious stimulation

How does tissue damage cause peripheral sensitisation?

Tissue damage causes release of chemical mediators from surrounding tissue

* Influence excitability of nociceptive afferent endings


* Activate free nerve endings, releasing neuropeptides
* Immune system cells release inflammatory mediators = neurogenic inflammation
* Acute/persistent changes → sensitisation

Persistent pain due to decreased nociceptor threshold during inflammation – A and C fibres respond differently

Mechanisms of central sensitisation

* Modification of phenotype of neurons
* Post translational modification and changes in expression after injury

Ectopic activity

Action potentials are generated spontaneously

Where can pain be modulated

* Spinal cord
* Trigeminal nuclei
* Brain

What is gate control theory of pain?

* Inhibition of pain by mechanical stimulation
* Non-painful input ‘closes the gate’ to noxious input
* Stimulation of touch receptors results in AB fibres activating inhibitory interneurons
* Inhibition of pain transmission via nociceptors

Example of gate control theory of pain

Bump head, rub head, activates touch fibres and inhibitory interneurons in spinal cord

How does descending control of pain occur for dental pain?

__Trigeminal complex__

* Project to trigeminal nuclei and inhibit response to noxious stimuli
* Release neurochemicals in nucleus caudalis (serotonin) and interneurons in nuclei complex (GABA, enkephalins)

Hoe does descending control of pain occur for body pain

Spinal cord

* PAG projections to the nucleus raphe magnus (NRM) – descending autonomic tracts
* Contains encephalin-producing cells that suppress pain
Inhibition of nociceptive transmission by
* Postsynaptic inhibition of DH/trigeminal neuronal activity
* Presynaptic inhibition of neurotransmitter release from C nociceptors

Central sensitisation is due to…

increased excitability of nociceptive neurons in CNS induced by nociceptive afferent barrage into CNS after tissue injury