Neurophysiology Flashcards
describe the basic pathway of pain to the brain
- Stimulus activates a receptor (Temperature, pain, touch & pressure receptors)
2) Action potential (AP) elicited in nerve
(called Dorsal Route Ganglion nerves or DRG)
3) AP enters spinal cord and synapses onto an ascending nerve in the Dorsal Route Horn.
4) Nerves travels across the spinal cord (crosses over) and ascends to the brain (usually via the thalamus).
5) Signal travels to the sensory cortex where it is processed and acted upon
describe the difference in myelinated and unmyelinated neurones in pain
Myelinated neurones (A δ):
- Rapid conduction velocity (6 to 30 m/s)
- fast pain
- Sharp
- Seems immediate
- Highly localised
- Superficial tissue
Unmyelinated neurones (C)
- Slow conduction velocity (0.5 to 2 m/s)
- slow pain
- Dull
- Delay (tends to linger)
- Hard to locate
- Superficial and deep tissue
briefly describe the Gracile fasciculus - A δ fibres nociceptor pathways
pain in kidneys
sends signal to spine
but it travels up the same side of the spine that the pain is - only crosses over the. it gets to the nucleus in the medulla
hard to tell exactly where the pain is
Facial nerves (Trigeminal) - C fibres - describe their nociceptor pathway
unmeyelinated
duller pain - pain in gums teeth and in jaw
pathway leads directly into the brain - doesn’t pass through spinal cord
Why would it be advantageous to inform the hypothalamus of injury when a person is in a potentially harmful situation?
fight or flight, descending analgesic pathway
The hypothalamus is part of the limbic system, which is associated with emotion, does this area therefore contribute to nociception or pain perception?
pain perception
describe referred pain and its cause
pain felt in “wrong area”
pain felt where there isn’t a problem
cause:
- nerve from organ and skin enter dorsal root ganglion close together
- when the signal is sent to the brain it can’t discriminate between the two
- so associates the pain in the organ with the skin of the nerve
difference between acute and chronic pain
ACUTE: Physiological: - Nociceptive and inflammatory - Sudden onset in response to a discrete event - Recedes during healing
CHRONIC:
Pathological:
- Neuropathic
- Persists long after recovery (> 3 months)
- Often difficult to tie to a specific event
- Often unresponsive to analgesics
describe neuropathic pain
Occurs as a result of a lesion or disease in the P/CNS – change in neurone not the tissue
Eg diabetic neuropathy, multiple sclerosis, fibromyalgia or spinal cord injury
May be associated with allodynia or hyperalgesia
Hyperalgesia – increased intensity of pain sensation for a given nociceptive stimulus
Allodynia – sensation of pain in response to something not normally painful in nature – eg light touch near a wound
Due to sensitization of peripheral and central neurones
Peripheral sensitization:
- Increased sensitivity of C and Aδ fibres due to prostaglandin release
- Increased voltage dependent Na+ channel expression - more likely to form an action potential to send pain
Central sensitization:
- Increased glutamate release because of peripheral sensitization
- Increased expression of glutamate receptors (NMDA receptor subtype)
o Hyperalgesia
- Sprouting of Aβ (mechanoreceptor) fibres to make new connections
o Normal sensation of pressure now perceived as painful
o Allodynia
Phantom limb pain:
- A type of neuropathic pain
- Reorganization of cortex - confusing because then sensors from other parts of the body like the face or feet start sending signals to the part of the brain that used to hold info for the arm - so therefore person may be actually stimulated on their face but they feel the pain in their face and also their ‘arm’ even though their arm is no longer there
- Sensitization
Question: How could the increased expression of Na+ channels cause an increase in nociceptor sensitivity?
Increased likelihood that the threshold potential will be reached
describe phantom limb pain
Phantom limb pain:
- A type of neuropathic pain
- Reorganization of cortex - confusing because then sensors from other parts of the body like the face or feet start sending signals to the part of the brain that used to hold info for the arm - so therefore person may be actually stimulated on their face but they feel the pain in their face and also their ‘arm’ even though their arm is no longer there
- Sensitization
describe the levels of integration of the brain/spinal cord
So reflexes integrated on a spinal level are simple, concerned with basic survival of the animal such as homeostasis, basic locomotory circuits, postural control and stereotypical behaviour.
Step up one level to subcortical reflex integration and things are a little more advanced. Feeding and drinking behaviours are integrated here, our sexual and instinctual activities being strongly influenced by this more primitive brain area.
Finally humans and other primates have large cerebral cortices. Neural control integrated on a cortical level is quite advanced. The cerebral cortex of man, one could opine, is the apogee of evolution, being the seat of intellect, art, literature, philosophy and science. It certainly is the highest level of neural integration in the healthy human.
describe what the hippocampal system is made up of and its function
Limbic cortex, Hippocampus, fornix, mamillary body
Cognition and interface of intellect and emotion
Memory formation
describe what the amygdaloid system is made up of and its function
Amygdala, Olfactory bulbs, medial forebrain bundle
- more central than hippocampal
Emotional expression, sexual drives
Strengthen memories
- Smells
- Emotions
Motivation and reward
Describe the descending pathway and explain how its activation causes analgesia
Identify circumstances when analgesia may be naturally effective
Identify four types of pharmacological analgesics and explain how they work
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Describe the descending pathway and explain how its activation causes analgesia
- the pathway starts with the activation of neurones in the periventricular nuclei (PVN) of the hypothalamus.
- Signals are relayed from this area to the periaqueductal gray (PAG) of the mesencephalon and upper pons,
- then from here to the raphe magnus nucleus (RMN) of the pons.
- From the RMN signals eventually reach the inhibitory interneurons, in the dorsal horn of the spinal cord, serotonin mediates neurotransmission between these neurones.
- In response, the neurotransmitters GABA and enkephalins (the body’s endogenous opioids) are released by the inhibitory interneurones to prevent signals being carried any further by the 2nd order projection neurones. - GABA prevents transmission by opening Cl- channels on the postsynaptic DHN cells and causing hyperpolarisation – reduces the firing of APs in the DHN.
- Enkephalin activates opioid receptors expressed by the:
o Aδ and C fibres
o Dorsal horn neurones - Reduced transmission of nociception by 2 actions:
1. Enkephalins inhibit DHN depolarisation by opening K+ channels - K+ moves out and the DHN is hyperpolarised
2. Act presynaptically to inhibit the opening Ca2+ channels - Reduced Ca2+ entry means less transmitter release
Identify circumstances when analgesia may be naturally effective
- Relaxation techniques to increase encephalin and serotonin release centrally
- Transcutaneous electrical nerve stimulation (TENS) – stimulating peripheral inhibitory pathways by releasing enkephalins
- Application of pressure - does rubbing an injury ease the pain?
How does rubbing an injury ease the pain?
Inhibitory interneurones can also be activated by Aβ fibres which are activated during mechanosensation, hence rubbing an area after injury or waxing for example produces a natural analgesia.
Heat and cold treatments for pain
Heat treatments, such as heating pads or warm baths, tend to work best for soothing stiff joints and lower back pain by increasing blood flow and relaxing muscles. A cold pack or ice application can reduce inflammation (via reduced blood flow) and nociceptor activation. Nociioceptors and Aβ fibres may also be thermosensitive. However little conclusive scientific data is available to prove efficacy!
describe the use of opioids as analgesics
E.g morphine, pethidine, codeine
These analgesics can inhibit transmission of pain signals at the level of the spinal cord by activating the same opioid receptors that the endogenous enkephalins do. They can also activate the descending pathway by stimulating RMNs (normally activated by enkephalins released from PAG neurones in the pons) and hence activate inhibitory interneurons to reduce DHN activation.
- Extremely effective analgesic but also huge potential for addiction.
- Generally used for surgical pain, child birth or pain that doesn’t respond to any other drugs.
Side effects:
- Dependence – physical and psychological
- Euphoria/sense of well-being - helpful in terminal pain, as can be the sedative effect.
- Constipation – opioid receptors in the gut oppose parasympathetic activation of contractions
- Nausea and vomiting - stimulation of the chemoreceptors in the medulla
- Respiratory depression - reduction in the sensitivity of the respiratory centre to CO2
- Withdrawal symptom may include nausea, muscle aches, diarrhoea, trouble sleeping or a low mood.
describe the use of NSAIDs as analgesics
watch slides 17 and 18 of pain - analgesia lecture 12
Inflammation => ↑Prostaglandins => Hyperalgesia (sensitize nociceptors)
NSAIDs inhibit COX (COX-1 & COX-2) E.g. Aspirin, ibuprofen
↓Prostaglandins ↓Hyperalgesia
Inhibiting COX - Adverse effects:
- Na+ & H2O retention (↑BP)
- GI bleeding
- stroke, MI
describe the use of Local Anaesthetics (LAs) as analgesics
- Local anaesthesia - induce the absence of sensation in a specific part of the body.
- It allows patients to undergo surgical and dental procedures with reduced pain and distress.
- Anaesthetists sometimes combine both general and local anaesthesia techniques.
- Blocking the initiation and propagation of the action potential by pain fibres
- Local anaesthetic (LA) enters the cell, is ionised and binds to Na+ channels closing the inactivation gate – no new action potentials can be transmitted.
- If the LA is already ionised its entry into the cell is restricted to entry via the pore of the channel
- Common side effects include: nausea, dizziness, bruising, redness, itching, or swelling where the medication was injected.
- Less common but serious side effects include: drowsiness, mental/mood changes, ringing in the ears, vision changes, tremors, numbness, headache, or backache.
- Na+ channels are throughout the body and LAs can spread
How might bacteria, which produce acidic by-products, effect the efficacy of LAs?
More ionised LA outside - block reliant on LA entering the cell via the channel pore
= Reduced effectiveness
Why might LAs be given in conjunction with a vasoconstrictor eg adrenaline?
To confine the spread to other tissues and reduce blood loss
describe the use of antidepressants as analgesics
- ↑Serotonin levels in the synaptic cleft
- ↑activation of descending analgesic pathways
- => less nocioceptive signals passed to DHNs.
- Also help break the vicious circle of psychological and physical effects of pain.
- Particularly helpful in management of chronic & neuropathic pain.
