Pain Flashcards
Describe the anatomy of the sensory nervous system Understand the gate control theory of pain Identify the key molecules involved in pain pathways Understand how voltage-gated sodium channels are involved in pain pathways
Describe cutaneous somatic pain
Pain from the body surface, felt as a sharp and burning sensation
Describe deep tissue somatic pain
Pain from the musculoskeletal system, usually felt as a dull or aching but localised sensation
Describe visceral pain
Pain originating from the organ tissues of the thorax, abdomen, or pelvis, felt as a deep dull, and vague sensation
Describe neuropathic pain
Pain caused by lesions of the nervous system that results in structural damage to nerve units instead of receptor stimultion, felt as a burning or stabbing sensation
Name four causes of neuropathic pain
Diabetes mellitus, chemotherapy drugs, antiretroviral drugs, HIV
Describe phantom pain
Sensations of burning or tingling felt in an absent body part
State four differences between acute and chronic pain
1) Acute pain is usually sudden-onset; chronic pain can be sudden or gradual in onset
2) Acute pain is self-limiting and resolves within 6 months, whereas chronic pain lasts over 6 months, with periods of remission and exacerbation
3) Acute pain usually has a precipitating event, whereas chronic pain is rarely associated with an injury
4) Acute pain usually resolves with treatment, whereas chronic pain is hard to treat
Where does pain occur?
The brain
Which neurons transmit most pain signals?
Dorsal root ganglia neurons
How is facial pain different to other pain?
It is transmitted by the trigeminal ganglion instead of dorsal root ganglia neurons
Which nerve fibres mediate acute pain, and which mediate chronic pain?
Acute: A-delta fibres
Chronic: C fibres
Define Descartes’ specific theory of pain
The intensity of pain is directly related to the amount of associated tissue injury
Define tactile allodynia
Extreme sensitivity to light touch
What causes touch sensitivity?
Dysfunctional inhibitory interneurons
Describe the role microglia play in interneuron nerve damage
Nerve damage causes signals to be sent to microglia, which activates them and causes them to proliferate around laminae I. If the signals persist, this leads to chloride-mediated hyperpolarisation, because the microglia release BDNF which leads to KCC2 (potassium-chloride co-transporter 2) downregulation and an inability to regulate the chloride ion concentration gradient. This means interneurons lose their inhibitory power, and can even become excitatory
Who proposed the gate control theory of pain, and when?
Melzack and Wall, 1960s
Define the gate control theory of pain
Pain messages can only get through easily when the gates are open. When the gates closed, pain messages are prevented from reaching the brain and may not even be experienced
Why can information on pressure and touch override information on pain?
Tactile information is carried by faster A-beta fibres, whereas pain is carried by slower A-delta and C-fibres. This means touch information reaches the brain first and can override later messages
How many laminae are the cells of the spinal cord arranged in, and where are they?
10 - six in the dorsal horn, three in the ventral horn, and one clustered around the central canal
In which spinal cord laminae do C fibre nociceptive afferents terminate?
Laminae I and II (dorsal horn)
In which spinal cord laminae do A-delta fibre afferents terminate?
Laminae I, II, and V (dorsal horn)
In which spinal cord laminae do A-beta fibre afferents terminate?
Laminae V and VI (dorsal horn)
Name the major brain areas involved in pain perception
Primary and secondary sensory cortices, anterior insula, and cingulate gyrus
What is bradykinin?
A polypeptide made from kininogen by proteolysis in the blood, in response to tissue damage or coagulation
What type of receptors are the bradykinin receptors B1 and B2?
G-protein coupled receptors
Which receptor do prostaglandins bind to, and where is it located?
EP2 at free nerve endings
Name three cells which release prostaglandins in response to tissue damage
Granulocytes, macrophages, and nociceptive neurons
Name the rate-limiting enzyme of prostaglandin synthesis
Cyclo-oxygenase (COX)
State the function of nerve growth factor (NGF) in pain
It regulates the peripheral sensitivity of nociceptive neurons and increases functional sodium channel expression
State the consequence of increases levels of NGF to pain
Mechanical and thermal hyperalgesia
Name the receptors NGF binds to, and where they are located
TrkA receptors - single-TM tyrosine kinase receptors selectively expressed in unmyelinated nociceptive sensory neurons
Why is NGF a good target for analgesic drugs?
While it is necessary for development, it is non-essential in adults
Name three tachykinins
Substance P, neurokinin A, neurokinin B
What is the main inhibitory neurotransmitter?
GABA
State three neurotransmitters involved in descending pain regulation
Noradrenaline, serotonin, enkephalins, and endorphins
Why is the NMDA receptor inactive without glutamate?
It is physically blocked by a magnesium ion sitting in its ion channel
Name three substances produced by the NMDA receptor
C-fos, prostanoids, and nitric oxide
In which spinal cord laminae is GABA highly expressed by interneurons?
Laminae I, II, and III (dorsal horn)
How do GABA-ergic neurons mediate gate control in the dorsal horn?
They synapse on neurons containing glutamate and substance P (excitatory neurotransmitters)
What is the difference between the GABA-A receptor and the GABA-B receptor?
GABA-A: Ligand-gated calcium channel
GABA-B: 7-TM G-protein coupled receptor
Name three stimuli which activate TRPV1
Capsaicin, noxious heat over 43 degrees Celsius, low pH
Why can capsaicin activate TRPV1?
It has a similar structure to the endogenous ligand anandamide
Where is TRPV1 exclusively expressed?
Nociceptive sensory neurons
Name two stimuli which activate TRPM8
Cool temperatures (8-28 degrees Celsius) and menthol
State the pre-cursor of anandamide, and its molecular class
Arachidonic acid, an omega-6 fatty acid (pro-inflammatory)
Why are ATP-gated channels found on nociceptive neurons?
ATP is only found extracellularly after cell damage
Which ATP-gated channel results in the release of BDNF?
P2X4
Which are the key ion channels for action potential production?
Sodium channels
What role does the alpha2delta subunit play in the formation of voltage-gated sodium channels?
It acts as a chaperone for the trafficking of the alpha1 subunit from the Golgi to the membrane
How many voltage-gated sodium channels are there in the human body?
10 (9 main)
