Flashcards in Neural mechanism of pain Deck (71):
What is a nociceptor?
A nociceptor is a receptor of a sensory neuron (nerve cell) that responds to potentially damaging stimuli by sending signals to the spinal cord and brain
What stimuli in the periphery can activate a nociceptive afferent neuron?
- A noxious mechanical stimuli (harmful) e.g. a hammer
- A noxious heat and chemical stimuli e.g. fire/ chilli
What are nociceptive afferent neurons?
These are small diameter primary afferent fibres of the peripheral nerves. They are sensory nerves and have a high threshold for mechanical and thermal reception compared to other sensory nerves. Therefore, are activated by noxious stimuli. The noxious stimuli activates both non myelinated C fibres and myelinated Adelta fibres.
Noxious stimuli activate what?
The noxious stimuli activates both non myelinated C fibres and myelinated Adelta fibres.
What are the four types of primary afferent neurones?
List the order of axon type from most myelinated to not myelinated at all (largest diameter to smallest diameter)
Which axon conducts the slowest and why?
C. it non myelinated therefore has the slowest conduction due to lack of saltatory conduction
Which axon conducts the fastest?
What are A-alpha fibres known as? What do they detect?
What are A-beta fibres known as? What do they detect?
What are A-delta and C fibres known as? What do they detect?
Nociceptors. Painful stimuli i.e, temp; heat or cold - frostbite, lactic acid (chemical)
being hit by a hammer (mechanical)
Explain how and where mechanocetor or proprioceptor fibres travel?
The neurones travel to the dorsal root ganglia, where the stimulus is translated as non noxious stimuli rather than noxious. The neurone carries the signal to the spinal cord and goes straight the the dorsal column nuclei.
Explain how and where nociceptor fibres travel?
The nociceptor detects the painful stimulus and carries the signal to the dorsal root ganglia where it is translated as noxious. The signal is carried to the spinal cord, where it synapses at the substantia gelatinosa, with an afferent neurone (secondary neurone) and crosses over to carry the signal to the spinothalamic tract.
A beta innervates lateral
A delta innervates lateral
1 and 5
C fibre innervates lateral
PHYSIOLOGICAL PAIN (ACUTE)
Nociceptors respond to acute tissue-damaging stimuli either directly, through ___ channels on nerve terminals, or indirectly, through activation of TRP channels on keratinocytes (for example, _____) and/or the release of intermediate molecules (such as ____).
Cold _____ acts on _____ channels on nerve terminal
Heat acts _____ AND _____.
The direct way, it acts on _____ channels on the nerve terminal. The indirect way it acts on _____ channels on keratinocytes.
H+ acts _____ on _____ and _____ channels on the nerve terminal
Mechanical stimuli act ______ and directly. They act indirectly, through releasing ____ and then acting on ____/_____ channels.
They also act _____ by acting on ____ channels
INFLAMMATORY PAIN (CHRONIC). After tissue damage, _____ ___, _______ and _______ are activated. Various immune mediators are released which exert their algesic effects by acting directly on nociceptors or indirectly through the release of other mediators, most notably prostanoids.
Where are the cell bodies of these neurones located?
DRG (but also trigeminal ganglia)
Example of external tissues where these nociceptors are present?
Example of internal tissues where these nociceptors are present?
The trigeminal ganglia are specialized nerves for the face, whereas the dorsal root ganglia associate with the rest of the body.
a completely non-noxious stimulus like light touch causes extreme pain
low intensity stimuli from regular activity, initiates a painful sensation
What are the excitatory neurotransmitters for C fibre?
CGRP (calictonin G-related peptide)
What is the difference in how acute pain is treated and how chronic pain is treated?
Acute pain is treated with local/general anaesthetics.
Chronic pain e.g. allodynia/ hyperalgesia is treated with NSAIDS, opiates, anticonvulsants
which component causes hyperalgesia?
which component causes allodynia?
Explain the peripheral component.
Cause of hyperalgesia. Excitatory neurotransmitters such as Substance P, Bradykinin and Prostoglandins excite neurones, creating an action potential to be generated and sent to spinal cord, and then the brain. This is detected as pain. Treated with NSAIDS.
Explain the central component.
Cause of allodynia. Due to temporal summation of successive noxious stimuli, thus increasing the amplitude.
Name some stimuli/ neurotransmitters that activate neurnones
What receptor does Bradykinin bind on?
What receptor does Serotonin bind on?
What receptor do lipids bind on?
What enzyme do corticosteroids inhibit in order to stop PG production?
What enzyme do NSAIDs inhibit in order to stop PG production?
COX-1 and COX-2
How do local anaesthetics stop nerve conduction?
They block Na+ channels therefore the nerve cannot depolarise.
No action potential. No message transmitted. No pain
Local anaesthetics have to diffuse into the cytoplasm as a free base in order to block Na+ channel from the inside.
This is because it does not bind from the outside. Therefore it needs to be in the non ionised form so that it can apss through then become ionised inside the cell and THEN bind to the receptor
In what structure are the interneurons retained?
The midbrain contains a structure known as
periaqueductal grey matter; PGS
The brainstem contains a structure known as
nucleus raphe magnus; NRM
Ascending nociceptive nerves not only transmit pain signals to the higher centres in the brain, but also make connections to
the midbrain (periaqueductal grey matter; PGS) & brainstem (nucleus raphe magnus; NRM)
The PGS and NRM help inhibitory ________ and produce a diffuse inhibition.
The descending central controls that are associated with more complex psychological phenomena, such as h____ and the p_____ response, that can reduce our perception of pain to varying degrees.
Interneurons contain enkephalins.
Name four endogenous opioids.
NRM neurone contains which neurotransmitter?
PGS neurone contains which neurotransmitter?
Which fibre type would excite the interneurones?
A-beta and A-alpha
What are the two ways you can activate you interneurones?
Your brain or the ascending fibres
How does the placebo effect work?
The brain thinks you are feeling better, and activates the PGS and NRM, which in turn activate interneurones. This is how you are able to inhibit the pain.
Dorsolateral prefrontal cortex works with which kind of psychological phenomena?
Hypnosis and placebo response. This can reduce our perception of pain to varying degrees
Interneurones release _______ which bind to _____ receptors present on the C fibres secondary neurone, and prevents it from ______-ing with the secondary neurone. It inhibits an ____ _______.
After spinal cord, where do the neurones message go?
How do the enkephalins release for interneurones work on the presynaptic terminal? (C-fibre)
- The opioid binds to mu receptor.
- Mu receptor activates inhibitory G protein.
- This inhibits adenylate cyclase
- So, cAMP is reduced
- Protein Kinase increase
-PKA inhibits Ca2+ channel
- Ca++ cannot enter
- vesicles with NT, therefore, are not released.
- AP is not transmitted.
Which neurone is the post synaptic terminal?
Secondary/ afferent neurone
Which neurone is the pre synaptic terminal?
Primary neurone (C-fibre)
How do the enkephalins release for interneurones work on the postsynaptic terminal? (C-fibre)
- Opioid binds to mu receptor
- This activates inhibitory G protein
- Gi opens K+ channels
- K+ leaves cell
- This causes repolarisation/ hyperpolarisation as + is leaving cell and becoming more -ve
- Depolarisation cannot occur
Which is faster acting? Naloxone or Naltrexone?
Name some effects of opiates.
Nausea & Vomiting
Histamine release from mast cells
What is neuropathic pain?
Chronic pain resulting from injury to the nervous system. The injury can be to the central nervous system (brain and spinal cord) or the peripheral nervous system (nerves outside the brain and spinal cord).
Name an anticonvulsant drug used for postherpetic neuralgia. (After herpes)
Name some anticonvulsant drugs used for diabetic neuropathy
Name some anticonvulsant drugs used for HIV associated neuropathy
Name some anticonvulsant drugs used for Trigeminal neuralgia (severe burning pain of face)
Name an anticonvulsant used for central post-stroke pain
WHAT ARE THE TWO CARDINAL SIGNS/SYMPTOMS OF NEUROPATHIC PAIN?