Sensory motor neurotransmission (finished) Flashcards
Where are the cell bodies of sensory nerves located?
dorsal root ganglion
Where are the terminals of sensory nerves located?
2 terminals
- Various tissues and organs round the body e.g. skin = peripheral terminal
- Other ending is within the CNS = central terminal
What is the basic role of sensory neurons?
Pick up information and convey to CNS- part of reflex arc, then motor nerves are activated to illicit a response e.g. pain
Name + define the 2 types of functions of sensory nerves
Afferent function = sensation and reflex homeostasis
Efferent function = motor function involves release of neurotransmitter from peripheral terminals (typically neuropeptides) in response to a stimulus that can also illicit a response that travels through collaterals so neurotransmitter can be released at adjacent terminals e.g. skin- antidromic vasodilation = neurotransmitter released at blood vessels and causes them to dilate
What are the different names for sensory nerves?
C and A delta fibres
sensory-motor
Primary afferent
How were sensory nerves discovered (1876-1927)?
- 1876- Stricker (scientist) found if you cut nerve trunk to separate endings from cell bodies- then stimulate bottom half of nerve fibre = response in the periphery = suggests nerves could convey information in efferent direction
- 1901- Bayliss (scientist) found if you destroyed dorsal root ganglion = prevent response (vasodilatation) but if you did this to sympathetic ganglion = did not prevent vasodilatation
- 1927- Lewis = 1st person to ascribe phsyiological role to these nerves as he showed stimulation of these nerves linked with neurogenic inflammation- as inflammatory response didnt occur when skin was denervated
What are the causes of an insect bite response?
Insect bite reponse =
- site of bite = raised area from sensory nerves releasing neurotransmitter onto blood vessels = become leaky and white blood cells accumulate
- Redness caused by sensory nerves releasing neurotransmitter into skin = blood vessels dilate
- Area is hotter = increased blood flow
- Pain = involves sensory function of sensory nerves
Name some other diseases that have been linked to sensory nerves
- Asthma
- Eczema
- Psoriasis
- Migraine
What was the compound used to discover most of what is known about sensory neurons?
capsaicin
What vegetable is capsaicin found?
Hot peppers
Historically, how was capsaicin used?
Added to sensory nerves =
- Low doses (µg/kg) – transient excitation
High doses (mg/kg) – long lasting damage in vivo = desensitises them
What is capasicin?
Vanilloid
What does capsaicin act on?
TRPV1 = non-selective cation channel that gets depolarised result in neurotransmitter release = desensitisation
What does capsaicin select for?
Selective for “capsaicin-sensitive” sensory nerves = Non-myelinated (C fibre) and some thin myelinated (Ad) axons
Capsaicin is not often present in the body, so what acts at TRPV1 channels?
endocannabinoids
Hydrogen ions
Where are sensory neurons found?
Can be found throughout the body- lungs, bladder i.e. in most organs and tissues
Describe the distribution of sensory motor nerves in the cardiovascular system
Wide distribution in cardiovascular system- many blood vessels and heart
Mainly adventitial (some medial) localisation.
Density of fibres generally higher in arteries than veins.
Capsaicin treatment
removes SP and CGRP
immunoreactivity
What are the neurotransmitters of the sensory nerves in the cardiovascular system?
substance P (SP)- and calcitonin gene-related peptide (CGRP)-containing fibres (more CGRP)
Where are sensory nerve fibres located on blood vessels?
Mainly adventitial (some medial) localisation.
What is the adventitia?
Outermost layer of blood vessels
Compare the density of sensory nerve fibres in arteries and veins
Density of fibres generally higher in arteries than veins
What happens when capsaicin is added to sensory nerves in cardiovascular system?
Capsaicin treatment
removes SP and CGRP
immunoreactivity
Where are the sensory neurotransmitters stored?
CGRP and SP stored in same vesicles
What are some other neurotransmitters in sensory nerves?
Other cotransmitters: ATP, bombesin/gastrin releasing peptide, cholecystokinin, dynorphin, galanin, leucin enkephalin, nitric oxide, VIP (DO NOT NEED TO REMEMBER ALL JUST BE AWARE) - all have different properties allowing different functions
Where are the sensory nerve peptides synthesised and then transported to?
Peptides synthesised in cell body and transported to peripheral endings of nerves
How are CGRP and substance P removed?
Via proteases that metabolise them
Explain this diagram
showing sensory neuron with varicostities with vesicles of neurotransmitter inside
When neurotransmitters (CGRP, SP, NKA) released they act on their receptors on smooth muscle (in this case)
- CGRP acts on Gs receptors
- SP acts of neurokinin receptors
Sensory neurons are activated by TRPV1 channels activated via capcaisin, endo-cannabanoids and hydrogen ions
+ can also be activated by other agents e.g prostagladins, bradykinins, ATP (P2X receptors), histamine = mainly inflammatory mediators
Who and when first identified a role for sensory nerves?
Lewis in 1927
What was the 1st identified role of sensory neurons?
Vasoactive afferent neurones are a system of first line defense against trauma
Describe how sensory neurons are fit for their role of being the 1st line of defence after trauma
Very suited due to their dual role
- through afferent function can detect pain sensation and induce reflexes if necessary
- through efferent function can attempt to combat the trauma via vasodilation and plasma extravasation = neurogenic inflammation
Outline a key component of neurogenic inflammation
Hyperemia & increased vascular permeability = facilitates delivery of leukocytes to infected area → resistance against further damage & aids repair.
Name the different components involved in neurogenic inflammation
- Arteriolar vasodilatation
- Increase in vascular permeability
- Modulation by co-released sensory neuropeptides
- Effects of SP & CGRP on monocytes/macrophages
define: Hyperemia
increased blood flow
Describe the mechanism of Arteriolar vasodilatation
Mainly through the action of CGRP which acts on smooth muscle cells and causes them to dilate- can be some involvement by substance P and mast cell histamines
= facilitates delivery of white blood cells to traumatised area
Describe the mechanism of plasma protein extravasation
= increase in vascular permeability = protein leakage into interstitial space
Through the action of substance P and other tachykinins NOT CGRP
Describe how neurotransmitters interact in neurogenic inflammation
Modulation of one neurotransmitters response by another neurotransmitter e.g. CGRP facilitates SP-induced increase in permeability
Describe some of the effects of SP and CGRP on monocytes/macrophages
- Release of inflammatory mediators including cytokines, prostaglandins, leukotrienes & thromboxanes = inflammatory mediators
- increased vessel diameter, permeability & afferent excitability (sensitization) = feedback mechanism
Is neurogenic inflammation beneficial?
Yes when it occurs acutely however if it uncontrolled and goes on for too long = chronic inflammation = sensory motor nerves become hyperactive & contribute to hyperalgesia & perpetuation of inflammatory response
Other than being involved in inflammation, what do sensory neurons also do?
Some evidence that sensory motor nerves participate in moment-to-moment control of blood vessel diameter.- just controlling blood vessel diameter not just during inflammation
Describe the mechanism of sensory neurons in controlling normal blood vessel diameter
Mainly involves CGRP- this causes vasodilatation through actions of receptors on smooth muscle = increased cAMP and activation of potassium channels
Also evidence for role of SP- also involved in vasodilatation but acts through endothelial neurokinin receptors
Much lesser role of NKA in contraction; smooth muscle NK2 receptors
Describe an experiment that provides Evidence for a role of sensory nerves in vasodilatation
Experiment carried out using rat mesenteric arteries that were perfused and changes in perfusion pressure was monitored
Upward deflection = contraction
Downward deflection = vasodilatation
Initially experiment started in the absense of Guanethidine- contractions produced when electrically stimulated. After capsaicin applied = contractions are bigger due to sensory nerve vasodilatatory response has been abolished
When blood vessels are electrically stimulated = downward deflection (=vasodilatation)
When tetrodotoxin applied and electrical stimulation is repeated = relaxations are abolished- suggesting relaxations are due to the action of nerves- But what kind of nerves??
To find out added capsaicin and when electrically stimulated = responses are abolished = suggests involvement of sensory nerves
What is tetrodotoxin?
Blocks nerve transmission
What does Guanethidine do and why was is used in the experient showing involvement of sensory neurons in vasodilatation?
blocks sympathetic neurotransmission- used in the experiment to block out sympathetic contractial responses aas this would be the main response after electrical stimulation
BUT not interested in this instead wanted to focus of sensory nerve involvement
What does Methoxamine do and why was is used in the experient showing involvement of sensory neurons in vasodilatation?
= alpha 1 agonist that is involved in contraction to optimise vasorelaxation
Added to create background level of contraction as this was the response of interest
Describe other parts of the experiment showing the role of sensory nerves in vasodilatation
Used CGRP receptor antagonist that also blocked relaxation responses = showing involvement of CGRP
If you added a mimic by exogenous CGRP = caused vasodilator response mimicking actions of sensory nerves
Collected perfusate before and during electrical stimulation, then assayed (ELISA + RIA) for CGRP and found that CGRP levels were raised during electrical stimulation
Immunohistochemical staining to show presence of CGRP in nerves
What is another thing that sensory neurons are involved in?
Regulation of cardiac function
How do we know that sensory nerves are involved in the heart?
Capsaicin is a potent cardiostimulant – positive inotropic & chronotropic effects due to activation of sensory motor nerves.
Measure CGRP, SP & NKA coreleased from cardiac sensory motor nerves.
apply exogenous CGRP = mimicks actions of capsaicin (SP inactive; NKA – negative inotropic & chronotropic effects).
What do cardiac sensory motor nerves do?
Cardiac sensory motor nerves activated by mediators of inflammation & ischaemia- has an inflammatory role but in the heart
What are trophic effects?
Longer term effects
Outline the trophic effects of sensory motor neurons
- Maintenance of tissue integrity & ability to repair in response to injury.
Wound healing:
destruction of sensory nerves reduces survival of skin flaps & leads to appearance of skin wounds.
SP, NKA & CGRP stimulate proliferation of endothelial & smooth muscle cells & skin fibroblasts
Influence on sympathetic nerves:
↓ sensory motor nerves - ↑ sympathetic nerves
Due to competition of nerves for nerve growth factor
Name some things that sensory nerves are involved in
- ageing
- hypertension
- diabetes
- migraine
How are sensory neurons involved in ageing?
blood vessels (mesenteric arteries) from aged rats = CGRP content and vasorelaxation is decreased
How are sensory neurons involved in hypertension?
sensory neurogenic vasorelaxation is decreased in mesenteric arteries of hypertensive rats
How are sensory neurons involved in diabetes?
sensory nerve conduction velocity, neuropeptide content & neurogenic vasorelaxation are decreased
How are sensory neurons involved in migraines?
CGRP-involvement of mediated vasodilatation; triptans
Explain this diagram
= summary of everything that has been covered:
- afferent function = picks info up from periphery and taking part in reflex homeostasis
- Not only function- also have efferent / motor function which can contribute to response by releasing neurotransmitters at peripheral terminals
- Main neurotransmitters of sensory motor nerves = CGRP and substance P with some involvement from NKA
- What activates sensory nerves? = mainly inflammatory mediators
At blood vessels- have both sympathetic (involved in contraction) and sensory nerves (involved in relaxation)
- balance between the two controls blood vessel diameter- if anything impacts sensory nerves = sympathetic function is going to dominate = contributing to raised blood pressure
