W5 E TEST - WEEKS 1-4 Flashcards
Define pain - IASP definition
“An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”
define nociception
Nociception is a subcategory of somatosensation. Nociception is the neural processes of encoding and processing noxious (harmful) stimuli.
define nociceptive pain
Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors.
define neuropathic pain
Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system.
Neuropathic pain is a clinical description of pain and is not a diagnosis.
define nociplastic pain
pain which is caused by ongoing inflammation and damage of tissues, and neuropathic pain.
The mechanisms that underlie this type of pain are not entirely understood, but it is thought that augmented CNS pain and sensory processing and altered pain modulation play prominent roles
briefly explain the difference between nociception and pain.
Pain is a subjective experience reported by a patient (a symptom), whilst nociception is the encoding and perception of noxious stimuli (a process).
- You can have neuropathy without pain
- but you cant have neuropathic pain without neuropathy
Describe peripheral sensation
Peripheral
- changes related to nerve fibres in the peripheral, in particularly the reduction of the threshold noxious innervation and/or the magnitude of the stimuli.
Descending modulation of nociception
PAG + Rostral Ventral Medulla
- can enhance/inhibit nociceptive sensitisation - based on stress response - can potentially release stress-reducing neurochemicals such as opioids or serotonin
Descending inhibition of nociception
Input from large myelinated Abeta fibres (touch sensation)at the spinal cord can reduce the transmission of nociceptive signal from the periphery to the brain, by activating inhibitory interneurons– (anti - nociceptive effect)
Mechanisms that heighten nociceptive processing (3)
other factors increasing sensitisation
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inhibition of hyperpolarisation
- neurochemicals present in inflammation prevent this period where there is no action potential (hyperpolarisation), therefore nociceptive input is constant.
-
activation of silent nociceptors
- the activation of high threshold nociceptors occurs
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increased chemical production
- release of trophic (growth) factors - NGF, BDNF
- increase production of receptor proteins
- increased production of neurotransmitters
Gate control theory of pain (Pain gate theory)
Input from large myelinated Abeta fibres (touch sensation)at the spinal cord can reduce the transmission of nociceptive signal from the periphery to the brain, by activating inhibitory interneurons– (anti - nociceptive effect)
Ectopic pacemakers in neuropathic pain
- ectopic ‘pacemakers’ generate spontaneous pain
- Produce an ‘emergency’ stimuli in surrounding nerves when an injury occurs
- happens from unmyelinated (damaged) parts of the axon - changed signals from damaged Schwann cells and glial (immune) cells
- this causes a reduction in action potential threshold, leading to HYPERALGESIA
- This happens on pain fibres (Ad + C) but also AB fibres, so touch becomes very painful (ALLODYNIA)
nociceptive apparatus: Nociceptors
Nociceptors (Peripheral Pain Receptors):
Location: Nociceptors are specialized sensory receptors located in various tissues, including the skin, muscles, joints, and internal organs.
nociceptive apparatus: afferent fibres (2 types)
Primary Afferent Neurons:
Types:
Aδ Fibers: These are thin, myelinated nerve fibers that transmit sharp, well-localized pain sensations quickly. They are involved in the immediate response to acute injury.
C Fibers: These are unmyelinated, slower-conducting fibers responsible for dull, aching, or burning pain that is more diffuse and longer-lasting.
Pathway: The nociceptors convert harmful stimuli into electrical signals (action potentials) that are transmitted via these primary afferent neurons to the spinal cord.
Nociceptive apparatus: dorsal horn of spinal cord
role, neurotransmitters involved and process of modulation
Role: The dorsal horn of the spinal cord is the first major processing center for nociceptive signals. Here, the primary afferent neurons synapse with second-order neurons.
Neurotransmitters: Glutamate and substance P are the primary neurotransmitters involved in transmitting pain signals at this level.
Modulation: The dorsal horn is also a site where pain signals can be modulated by descending pathways from the brain (inhibition or facilitation) and by local interneurons.
nociceptive apparatus: relevant ascending tracts (2)
Spinothalamic Tract: This is the main pathway that carries pain and temperature signals from the spinal cord to the brain. Second-order neurons in the dorsal horn cross to the opposite side of the spinal cord and ascend to the thalamus.
- carries information regarding touch, pressure, temp, and harmful input
Spinoreticular Tract: This pathway also carries pain signals but is more involved in the emotional and arousal aspects of pain.
- decussates immediately, ends at reticular formation (in brainstem)
- important in carrying inforegarding autonomic control and motor function (sleep, alertness)
nociceptive apparatus: key areas of CNS (5)
Brain Regions Involved in Pain Perception:
Thalamus: Acts as a relay station, processing and transmitting nociceptive signals to various parts of the brain.
Somatosensory Cortex: Responsible for the conscious perception of the intensity, location, and quality of pain.
Anterior Cingulate Cortex (ACC): Involved in the emotional and affective aspects of pain.
Prefrontal Cortex: Involved in the cognitive evaluation and interpretation of pain.
Limbic System: Includes structures like the amygdala, which is involved in the emotional and memory-related aspects of pain.
nociceptive apparatus: descending modulators (2) and neurotransmitters involved in inhibition of pain signals
Periaqueductal Gray (PAG) and Rostral Ventromedial Medulla (RVM): These brain regions send descending signals to the spinal cord that can either inhibit or facilitate the transmission of pain signals.
Neurotransmitters: Serotonin, norepinephrine, and endogenous opioids are key mediators of descending pain modulation, often leading to the inhibition of pain signals at the spinal level.
Common peripheral neuropathies and causes (6)
diabetic neuropathy - occurs distally, metabolic disorder, caused by the degeneration of myelin around peripheral neurons
post-herpatic neuralgia (shingles) - infection
GBS, RA - auto-immune conditions
radiculopathy - compression of nerve at origin
peripheral lesion to nervous system - trauma
common central neuropathies and causes (4)
spinal cord injury - trauma, congenital stenosis, tumour
brain injury - trauma
MS - autoimmune condition
pst strokes - lifestyle choices, idiopathic, genetically predisposed
components that contribute to increased neuropathic pain (centrally) (3)
enhanced central sensitisation
- hyper-excitability due to peripheral ectopic input
-also reduction in inhibition from spinal cord - reduced response to inhibitory neurotransmitters (opioids)
- the release of cytokines creates a pro-inflammatory environment, accelerating nociceptive potentials (overflowing cup analogy)
clinical features of neuropathic pain
- loss of function
- heightened mechanosensitivity via elongation or compression
- paraesthesia
- pain
- allodynia
- hyperalgesia
common neuropathic questionares
Orebro
PainDetect Pain Questionare
look at w4 powerpoint when released
define Radiculopathy
a neuropathy at the spinal nerve root which has a loss or impaired axonal conduction (not defined by pain).
Often caused by compression and/or irritation of the nerve root
define radicular pain
pain from the nerve root, evoked by ectopic discharges emanting from a dorsal root or its ganglion (from inflammation or compression) due to stimulation of peripheral axons or their cell bodies
define somatic referred pain
pain experienced at a site remote from its origin, caused by central sensitisation in spinal cord
positive and negative symptoms of neuropathic pain
Positive symptoms
- shooting, electrical shocks, burning
- cold hyperalgesia
- paradoxical sensations - ‘burning cold’
- touch allodynia
- dysaesthesias
- tingling, pins and needles, crawling feeling
- after sensations - prolonged pain
Negative symptoms
- numbness, loss of sensation
nociplastic pain symptoms
common symptoms:
- multifocal (varying) pain that is more widespread or intense, or both, than would be expected given the amount of identifiable tissue or nerve damage, as well as other CNS-derived symptoms, such as fatigue, sleep, memory, and mood problem.
what is central sensitisation
Central
- Increased responsiveness of nociceptive transmission neurons at the dorsal horn of the spinal cord to their normal or sub-threshold afferent input (not usually triggered by nociceptive input e.g cold, light touch, non-nociceptive input)
what are the key mechanisms (3) of peripheral sensitisation and what do they lead to? (3)
Key mechanisms
- increased receptors (upregulation)
- more neurotransmitters
- ‘silent’ nociceptors awoken (very high thresholds)
Leads to:
- increased quantity and magnitude of action pontentials
- inflammatory response
- reduced membrane potential threshold
what are the key mechanisms (3 - party analogy) of central sensitisation and what do they lead to? (2)
Key mechanisms:
- increased expression of neurotransmitters (glutamate, substance P, CGRP (excitatory neurotransmitters))
- increased expression of ion channel/receptors - NMDA receptors (increases efficiency)
- loss of inhibition - loss of inhibitory neurons and inhibitory neurotransmitters (GABA)
-
Leads to
- amplification of nociceptive signals
- non-nociceptive signals accessing nociceptive pathways
nociceptor function
Function: These receptors detect noxious (potentially damaging) stimuli such as extreme heat, cold, mechanical pressure, or chemical irritants.
nociceptor types
Types:
Thermal Nociceptors: Respond to extreme temperatures.
Mechanical Nociceptors: Triggered by physical damage or pressure.
Chemical Nociceptors: Activated by chemical substances released during tissue injury or inflammation (e.g., prostaglandins, bradykinin
neurotransmitters for activating an action potential (5)
- hydrogen ions
- potassium ions
- ATP
- Bradykinin
- Serotonin
neurotransmitters that sensitisers - they reduce membrane potential so a greater number of action potentials can be generated (4)
prostoglandin
histamine
Substance P
serotonin
relevant functions of PAG
- plays a role in the modulation of HR and BP
- processes fearful and defensive reactions
- has a role in analgesia
criteria for classifying nociplastic pain (4)
- pain,
- evoked pain hypersensitivity
- pain hypersensitivity to touch,
pressure, movement, or heat/cold - the presence of comorbidities
