Pain and descending control mechanisms 1 Flashcards
What are the 4 physiological mechanisms that make up Nociception?
- Transduction
- Transmission
- Perception
- Modulation
What is nociception?
Nociception = Sensation
usually nociception = pain, but not always as pain = perception.
Describe the process of Nociception.
The first is transduction of a stimulus, in the case of nociception a noxious stimulus such as excessive heat, into a generator or receptor potential which, if sufficiently large, will give rise to an action potential. This signal will be transmitted along the nociceptive pathways up to the brain. Here the signal can be perceived as pain, but this may not happen if the person is unconscious.
Are the dorsal root ganglion part of the PNS or CNS?
Peripheral nervous system.
Where are nociceptive inputs carried to in the brain and brain stem.
Particularly important are the rostral ventral medulla, the parabrachial nucleus, the periaqueductal grey, the thalamus and the amygdala. From the thalamus inputs are transmitted mainly to the somatosensory cortex, and from the amygdala to the insular and cingulate cortex. So nociceptive inputs are carried to a variety of areas of the brain.
What are 1st order nociceptive neurons also known as?
- Nociceptors
- Primary afferents
- Primary sensory neurons
What type of nerve fibres are Nociceptors?
A alpha, A beta, A delta or C?
Nociceptors are predominantly c-fibres (the majority of which are nociceptors) and the smaller A fibres, called A delta.
Which nociceptors have the slowest conduction velocity (CV)?
C-fibres conduction velocity is so slow, that it would take at least one second for a stimulus applied to a toe to reach the spinal cord. (6–25 and ∼1.0 m s−1, respectively)
What directly affects conduction velocity in nerve fibres?
- Their conduction velocity is directly related to fibre diameter. Most nociceptors are either Aδ or C fibres
- A delta fibres have a conduction velocity at least 10 times faster than C fibres
What are 2 factors that affect the quality / type of pain generated by nociceptors?
- The fibres its made up of; Stimuli travelling along A delta account for the first (fast) pain and those travelling along c-fibres for the second (slow) pain responses to injury.
- Also partly due to their receptive fields:
A delta fibres They receptive fields are small and do not overlap. Where as c-fibres Their receptive fields are large and have a significant overlap, so that it is harder for the brain to identify the specific location a stimulus applied to the area of overlap. - As a consequence, activation of A delta fibres gives rise to sharp, well localized pain, and activation of C fibres gives rise to dull, diffuse second pain.
What are 2 factors that affect the quality / type of pain generated by nociceptors?
- The fibres its made up of; Stimuli travelling along A delta fibres account for the first (fast) pain and those travelling along c-fibres for the second (slow) pain responses to injury.
- Also partly due to their receptive fields:
A delta fibres They receptive fields are small and do not overlap. Where as c-fibres Their receptive fields are large and have a significant overlap, so that it is harder for the brain to identify the specific location a stimulus applied to the area of overlap. - As a consequence, activation of A delta fibres gives rise to sharp, well localized pain, and activation of C fibres gives rise to dull, diffuse second pain.
How are certain stimuli only able to trigger certain nociceptors?
(Reminder about the the neurochemical and electrophysiological heterogeneity of sensory neurons responsive to noxious stimuli.)
- DRG neurons express a variety of distinct neurochemical markers, and Nociceptors make up 70-80% in the lumbar DRG, most of which are C fibres but there are different types of C fibres, as some are peptidergic or non-peptidergic.
- So certain stimuli will trigger certain nociceptors.
- Several receptors for chemical signals are instead G-protein linked receptors. They are not channels, so cannot depolarize the cells directly, but they can phosphorylate ion channels. This phosphorylation can activate the channel, or instead sensitise it, that is reduce their threshold of activation or increase their open probability.
- Some chemical receptors are G-protein linked receptors that phosphorylate and
activate ion channels.
What are the 4 main modalities of nociceptors?
- Thermal nociceptors (10% C-fibres)
- Chemical sensitive nociceptors. (Algogens, pH, irritants)
- Polymodal nociceptors (Thermal, mechanical, chemical)
- Mechano receptors
How do nociceptors encode stimulus intensity?
Nociceptors encode stimulus intensity by increasing the frequency of axon potentials
The frequency of action potential firing triggered by a stimulus can vary, what causes this variation?
- Many cells in the tissue, including mast cells, macrophages, keratinocytes, and T cells, all release a molecule called NGF.
- Simpler explanation is NFG will bind to its receptors on the terminal nerve ending on the neuron, and can alter the number of action potentials produced by making it more sensitive, so produces more action potentials.
Full explanation below;
- NFG can then interact with its receptors, (TrkA and p75)on the nerve endings. Bindings to the receptors activates intracellular signalling cascades that can modulate the activity of different ion channels in the nerve ending or can enhance the release of the neuropeptides, substance P (SP) and/or calcitonin gene-related peptide (CGRP). As a consequence, under normal conditions, a noxious stimuli might elicit a single action potential, whereas after treatment with NGF or more generally as a consequence of inflammation, the nerve now will give rise to multiple action potentials.
