1
Q
What is the definition of ADHD?
A
Developmentally inappropriate hyperactivity, impulsivity &/or inattention, leading to impairment in social, behavioural &/or academic
2
Q
What are the 3 subtypes of ADHD?
A
- Hyperactive/impulsive (15%)
- Inattentive (20-30%)
- Combined (75%)
3
Q
Describe the “Inattention” symptom group of ADHD?
A
- Does not attend
- Fails to finish tasks
- Can’t organise
- Avoids sustained effort
- Forgetful
- Easily distracted
4
Q
Describe the “Hyperactivity” symptom group of ADHD?
A
- Fidgets
- Runs/climbs excessively
- Cannot play/work quietly
- Always ‘on the go’
5
Q
Describe the “Impulsivity” symptom group of ADHD?
A
- Talks excessively
- Blurts out answers
- Cannot await turn
- Interrupts/ Intrudes others
6
Q
What are the additional co-morbidities/co-occuring problems associated with ADHD?
A
- Mental retardation
- Sleep disorders
- Epilepsy
- Reading/writing disorder
- Developmental coordination disorder
- Asperger’s
- Tic
- Oppositional defiant disorder (ODD)
- Sensory/Motor difficulties
7
Q
What are the functional impairments of ADHD diagnosis?
A
- SELF: low self-esteem, accidents, smoking, drugs, delinquency
- SCHOOL: difficulties, employment, underachieve
- HOME: stress, parenting difficulties
- SOCIAL: poor, relationship difficulties
8
Q
What is the global prevalence of ADHD?
A
~5%
9
Q
What is the “administrative prevalence” of ADHD in Scotland?
A
0.5%
10
Q
What is the male/female ratio of ADHD?
A
- 3:1 in population studies
- 10:1 in clinics
11
Q
What is increased prevalence of ADHD associated with?
A
Lower socioeconomic status
12
Q
What studies is there evidence of core symptoms of ADHD being highly heritable?
A
- Family pedigree studies
- Adoption studies
- Twin studies
- Linkage data
- Association analysis
13
Q
What does linkage data for ADHD suggest?
A
It’s associated with widely distributed
markers e.g. at chromosomes 4, 5, 6, 8, 11, 16, & 17
14
Q
What does association analysis for ADHD suggest?
A
Linkage with various dopamine receptor & transporter
genes, serotonin transport genes & others (Faraone et al 2005)
15
Q
What are the ante/peri-natal potential factors contributing to ADHD causation?
A
- Pre-term delivery.
- Smoking
- Alcohol
- Maternal stress
- Intrapartum asphyxia
16
Q
What are the postnatal potential factors contributing to ADHD causation?
A
- Brain trauma
- Epilepsy
- Deprivation/
attachment
17
Q
Where are the “Anterior attentional pathways” for ADHD?
A
- Frontal lobes
- Cingulate gyrus
- Basal ganglia (corpus striatum, esp. caudate nucleus)
18
Q
Where are the “posterior attentional pathways” for ADHD?
A
- Locus Caeruleus
- Cerebellum
19
Q
What does the imaging evidence base for ADHD show?
A
- Volumetric CT & MRI studies: reduced volume of key structures
- PET, SPECT, Functional MRI: reduced activation of key brain areas,
esp. frontostriatal
20
Q
What does the neuropharmacology evidence base for ADHD show?
A
Improved core symptoms in response to drugs which modify release & reuptake of key neurotransmitters (Dopamine & Noradrenaline), region specific for key brain pathways for self regulation & attention
21
Q
What does the neuropsychology evidence base for ADHD show?
A
Identifiable alterations & deficiencies in frontal lobe functions ie. working memory, executive function, focus, distractibility
22
Q
What is ADHD linked to?
A
Malfunctioning prefrontal cortex
23
Q
What prefrontal regions cause the 3 classical symptoms associated with ADHD?
A
- Impulsivity = orbital frontal cortex
- Hyperactivity = prefrontal motor cortex
- Inattention = dorsal anterior cingulate & dorsolateral prefrontal
24
Q
What is the role of Dopamine & Norepinephrine in information processing?
A
- Tune prefrontal cortex to make info processing efficient
- Too much/little DA/NE input disruptive in regulating cortical info processing
25
What are the 4 different management techniques for ADHD & ASD (multimodal/
multidisciplinary)?
1. Psychological/ behavioural
2. Educational
3. Social
4. Pharmacological
26
What % of ADHD symptoms persist into adulthood?
Upto 60%
27
What is the definition of Autism Spectrum Disorders (ASD)?
Highly variable & heterogeneous condition, with a wide range of aetiologies & phenotypes
28
What is the "triad of impairments" (Wing & Gould) of ASD?
1. Social communication
2. Social interaction
3. Social "imagination"
29
Describe Social communication impairments in ASD?
- Difficulties in verbal & non verbal communication (eye contact, facial expression etc.)
- Struggle in initiating & turn taking conversation
- May struggle to understand metaphor/ sarcasm & interprets language in literal manner
30
Describe the Social interaction in ASD?
- Development is different, delayed/ atypical with interaction difficulties
- Struggle with reciprocity, lack of empathy/failure to adapt their behaviour according to others perspectives & social context
31
Describe the Social "imagination" in ASD?
- Difficulties with thinking & behaviour
- Poor imaginative skills leading to restricted repetitive & stereotyped patterns
- Interests tend to be circumscribed & intense
- Routine & Structure
32
What is an issue for ASD children & young people?
Anxiety
33
Describe the epidemiology of ASD?
- Increased in last 20yrs, fall in other neurodevelopment disorders
- Atleast 1% of children have ASD (maybe 2%)
- ~50%+ children with ASD have intellectual disability
34
Describe the aetiology of ASD?
- Genetic influences
- Twin studies show high concordance for ASD in MZ versus DZ pairs
- 4 male:1 female
35
What, in the minority of cases (~10%), does ASD occur in association with?
Cytogenetically detectable chromosomal abnormalities & recognised genetic conditions (Fragile X, Down's syndrome, & Angelman’s Syndrome)
36
What can other family members of an ASD person have?
Relatively mild ASD-related social, communication & repetitive domain difficulties, termed as the broader autism phenotype (BAP)
37
What are the 4 clinically important other considerations in ASD?
1. Childhood onset epilepsy (30% by adolescence)
2. Sleep disorders (disrupted clock genes & dysregulatiion of melatonin)
3. Altered Motor function (cerebellar dysfunction, neural, hypotonia, clumsy)
4. Altered sensory function (hypo/hyper-responsiveness)
38
What is the pathophysiology of ASD?
- Infancy brain volume enlarged in 90%
- Macrocephaly in 20%
- Reduced size & distortion of neurones & intrinsic neuronal connectivity
- Widespread reduction in white matter volume & connectivity
39
What 3 things does suggested deficits in psychological processing & function in ASD include?
1. Impairments in frontal lobe mediated “executive functioning” & working memory
2. Deficiencies in “theory of mind”
3. Problems achieving “central coherence”
40
What is the overall mean heritability of ADHD according to Waldman & Gizer, Thapar?
~75%
41
What does the DSM 5 emphasise for ASD?
- Importance of early onset of signs & symptoms
| - Requirement to observe impairment in social, academic, behavioural, or occupational function
42
What is the % of sibling recurrence risk for ASD?
10%
43
What % of ASD cases has a copy number variation (CNV) been observed at submicroscopic level?
10-30% (mostly found in "rare" variants)
44
Can you have both ADHD & ASD?
YES
45
What are the qualities of sound detected by?
Amplitude & Frequency
46
What is high amplitude sound?
Loud
47
What is low amplitude sound?
Soft
48
What is the range or volume & frequencies detected by the human ear?
- FREQUENCIES: 20-20000Hz
| - VOLUME: 0-140
49
What volume causes physical discomfort in the ears?
100
50
What volume is the pain threshold?
140
51
Describe the general anatomy of the outer ear?
- Pinna
| - Tympanic membrane (connective tissue)
52
Describe the general anatomy of the middle ear?
- Air filled
- Malleus, incus, stapes
- Small muscles
- Auditory/ Eustachian/ Pharyngotympanic tube
53
Describe the general anatomy of the inner ear?
- Endolymph (scala media, semicircular canals, vestibule)
| - Perilymph (scala vestibuli, scala tympani)
54
What is force transduction?
Conversion of sound wave into neural correlate
55
Describe the 1st & 2nd transactions of sound waves?
1. (1st transduction) Strike tympanic membrane & become vibrations
2. Energy transferred to the 3 bones of the middle ear which vibrate
56
Describe the 3rd & 4th transaction of sound waves?
3. (2nd transduction) Stapes attached to membrane of oval window, vibrations create fluid waves within cochlea
4. (3rd transduction) Fluid waves push on flexible membranes of cochlear duct, hair cells bend & release neurotransmitter
57
Describe the 5th & 6th transaction of sound waves?
5. (4th transduction) Neurotransmitter release onto sensory neurons creates AP that travel through cochlear nerve to brain
6. Energy from waves transfers across cochlear duct & dissipated back to middle ear at round window
58
What happens to the basilar fibres along the length of the cochlea during different sound frequencies?
Structure changes from short & stiff to long & floppy, so resonant frequencies are graded along the cochlea
59
Where is high & low frequencies located in the cochlea?
- High: Base
| - Low: Apex
60
What happens when resonant frequency is activated in the cochlea?
Absorbs all kinetic energy of wave & effectively stops it at that point, other frequencies carry on
61
Describe the process of signal detection at the organ of Corti?
Upward deflection of the basilar membrane moves the inner & outer hairs laterally with respect to tectorial membrane
62
Where does 95% of the cochlea nerve endings terminate?
Inner hair cells even though there are less of them that outer hair cells
63
What does mechanical activation & neuronal signals from brainstem do to the outer hair cells?
Shorten & stiffen them to tune the cochlea by amplifying select frequencies
64
How does cochlea tuning occur?
- Inner hair cells depolarised & send signals to cochlea nerve then CNS
- Outer hair cells stimulated by basilar membrane to depolarise & causes cell to contract (& AP)
65
What doesn't mechanical displacement provide?
Sharpness of pitch discrimination, so there must be a system to enhance this
66
What is cochlea tuning also under?
- Active Olivocochlea neuronal control
- Fibers release Ach onto inner hair cells causing them to depolarise
- Effectively damps down hearing in areas of pitch no interest to listener (background noise)
67
Describe the effect of displacement of steriocillia?
One direction opens K channels & closes in the other
68
What happens when the stereocilia are displaced towards the tallest?
Stimulation (depolarisation)
69
What happens when the stereocilia are displaced away from the tallest?
Inhibition (hyperpolarisation)
70
Describe the processes which occur due to displacement of sensory hairs (stereocilia)?
- Channels constitutively open (baseline activity), can be enhanced/ diminished
- K+ enters at steriocillia, causes receptor generator potential, opens voltage gated Ca channels --> NT release onto appropriate nerve
71
What do outer hair cells act as?
Amplifier for vibrations at the organ of corti
72
What does Kanamycin (antibiotic) do?
Kills outer hair cells in specific point along cochlea, results in specific frequency hearing loss at that point
73
What happens when you knockout Prestin?
Loose 40-69decibels of hearing at that frequency i.e. outer hair cell amplifier provides a 40-60decibel gain in sensitivity
74
What is Prestin?
Cell membrane outer hair cell motility protein
75
Describe Otoacoustic emission?
- Sound comes out of ears
- 50% spontaneous
- Can be evoked, good tests for function up to inner hair cell
76
Describe how the signal gets to the auditory cortex in the brain?
- Upper medulla contains dorsal & ventral cochleal nucleus (1st order synapse)
- Some travelling ipsilaterally, most contralaterally upto inferior colliculus (most synapse)
- To medial geniculate nucleus of thalamus, fibres synapse & join auditory radiation to auditory cortex
77
Where are signals from both ears transmitted to?
Both hemispheres of the brain
78
Where do collaterals from the pathway (auditory) project to & why?
Reticulum of brainstem & vermis of cerebellum causing arousal responses to noise
79
Describe the characteristics of the termination of nerves from the cochlea?
Topographical relationship to the cochlea
80
What does the auditory association cortex receive?
Secondary projections from primary & some from thalamic association areas
81
Describe the tonographical arrangement of sound in cortical areas?
- Lower frequencies anterior in most maps
| - 6 variations of these maps per person, each fulfilling separate function of sound cognition
82
What are the 3 principle methods of directionality?
1. Volume
2. Sound shadow
3. Sound lag
83
Describe sound shadow?
- Sound from 1 side hits the head, which
generates sound shadow on other side in which the volume is less
- Comparison of signal intensities from both ears determines the ear closest to sound
84
Describe sound lag?
| owes for prey location
Sound from particular direction enters 1 ear before the other & slight delay between sound arriving ipsilaterally at the auditory cortex & contralaterally
85
What is sound lag better at determining?
Horizontal direction (lower frequencies) than sound shadow (high frequencies)
86
What detects front-back & above-below directionality of sound?
Folds in pinna which changes characteristics of sound
87
What are outer & middle ear deafness usually due to?
| conduction deafness
- Blockage of outer ear
- Infection in outer/inner ear
- Ossification of small bones in middle ear
- Rupture of tympanic membrane
88
What is the clinical significance of the Eustachian tube in infants?
Angle causes predisposition to middle ear infections
89
What is sensoneural deafness usually due to?
- Breakdown of cochlea & associated mechanisms
| - Damage to auditory nerve &/or auditory cortex
90
What are the 2 special tests for differentiating between sensoneural & conductive deafness?
1. Rinnes
| 2. Webbers
91
What does loss of association cortex lead to?
Loss of meaning of sounds such as those seen in Wernickes lesions, but not loss of differentiation of tone/frequency
92
What does loss of both primary auditory cortex areas cause?
Dramatically reduces sensitivity to sound
93
Describe the loss of 1 side of auditory cortex?
Much less effect as the auditory pathway runs bilaterally from the cochlea nucleus
94
What does Rinne negative & Ipsilateral (left) Weber suggest?
Left conductive deafness
95
What does Rinne (false) negative & contralateral Weber suggest?
Left sensory-neural deafness
96
What does (false) Rinne positive & Contralateral Weber suggest?
Left sensory-neural deafness
97
Where are 5 locations of the taste buds?
1. Tongue
2. Palate
3. Tonsilar pillars
4. Epiglottis
5. Few on proximal oesophagus
98
What are the 3 different types of papillae on the tongue?
1. Circumvallate (posterior in a V shape)
2. Fungiform (anterior surface)
3. Foliate (folds on lateral margins of the tongue)
99
Taste cells have been shown to be able to generate receptors that detect which 13 different chemicals?
- 2 potassium
- 2 sodium
- 1 chloride
- 1 adenosine
- 1 inosine
- 2 sweet
- 2 bitter
- 1 glutamate
- 1 H+
100
What are the 5 taste categories?
1. Sour- caused by H+
2. Salty- Na ions & K
3. Sweet- sugar, glycols, alcohols, ketones etc.
4. Bitter- alkaloids in toxic plants
5. Umami- L glutamate in meats & aged cheese
101
How do receptor types depolarise taste cells?
Either by inotropic or metabotropic pathways
102
Why is sensitivity to bitter tastes high?
Because they are generally indicative of a more dangerous substance
103
Describe the taste pathway to the cortex?
Via CN VII, IX, X principally to solitary nucleus, then thalamus, then insula & anterior operculum
104
What does the limbic component gustation activate?
Brainstem nuclei for salvation or vomiting
105
How is taste pain (from chilli or ethanol) carried?
From posterior parts of tongue in cranial nerve V (trigeminal)
106
What is the other main sensory input to recognition of foodstuff?
Olfaction
107
What is the olfaction system composed of?
- Olfactory epithelium
- Receptor cells (bipolar neurons)
- Axons that project through base of skull to olfactory bulb
- Neuronal tract to multiple olfactory destinations in the brain
108
What are the 3 steps to activation of the odorant receptor (7 transmembrane protein)?
1. Odorant molecule binds to receptor of primary olfaction neuron
2. Activates G protein which stimulates adenylyl cyclase to convert ATP to cAMP
3. cAMP activates cation channel, making it permeable for Na+ & Ca2+
109
What does activation of the odorant receptor cause?
- Cells to depolarise as generator potentials
| - Sufficient depolarisation leads to action potentials
110
What is the frequency of action potential generation in the odorant receptor proportional to?
Log concentration of the odorant
111
Describe the location of the lower end of the bipolar neurons?
Extends into layer of mucus secreted from Bowman gland in the olfactory epithelium, forming olfactory knob
112
What does the olfactory knob develop?
Olfactory cilia which detects odourants in nasal cavity
113
What is a special feature of the bipolar neurons in odour detection?
Continually develop & replace each other over time
114
Where is the olfactory bulb located?
- High in nasal cavity
| - 2.5cm squared area of olfactory epithelium
115
What are the 4 steps for information to be passed from the olfactory bulb to the cortex?
1. Info from bipolar cells to dendrites of mitral cells in neuropil of glomeruli in the bulb
2. Massive convergence, which helps ensure sensitivity
3. Also synapsing in glomeruli are Tufted cells which provide ‘lateral inhibition’ for signal enhancement
4. 2nd layer of lateral inhibition- Granule cells in bulb make dendritic connections between mitral cells
116
What is thought to be the case for glomeruli within the olfactory bulb?
Specific glomeruli respond to particular odorants in a dose dependent manner
117
How many genes are there in humans for different odorant receptors?
Over 300 (each bipolar neuronal expressed just 1 of these genes per neuron)
118
What are the 7 groups of odours?
1. Camphoraceous
2. Musky
3. Floral
4. Pepperminty
5. Ethereal
6. Pungent
7. Putrid
119
Describe the medial olfactory pathway?
- Ancient part of brain
| - Feeds into limbic system & encodes emotional aspects of olfaction & memory
120
Describe the lateral olfactory pathway?
- Feeds to ancient parts of brain (pyriform & pre-pyriform cortex in temporal lobe)
- Likes & dislikes for taste
- Visceral reactions via brainstem
121
Where does the lateral olfactory pathway NOT go via?
Thalamus
122
Describe the more recent olfactory pathway?
- Pass through thalamus & onto orbitofrontal cortex
- Involved with conscious discernment of odour & can be under conscious control for salience
- Works with limbic aspects of memory
123
What 3 things can cause nasal/sinus disease (25%)?
1. Colds
2. Polyps
3. Other blockages
124
Describe Parosmia (20%)?
Distorted often unpleasant sense of smell caused by damage to the lining at top of the nose (upper respiratory viral infections)
125
How common is congenital anosmia?
1%
126
How common is Alzheimer's preceding anosmia?
2-5%
127
How common is idiopathic anosmia's?
25%
128
What 3 things can head trauma anosmia (15%) lead to?
1. Damage to frontal lobe processing
2. Damage to ascending nerves at cribriform plate
3. Permanent compression of nasal passages
129
What is the definition of pain?
Unpleasant sensory & emotional experience associated with either actual/potential tissue damage, its subjective
130
What are the nociceptors 4 peripheral aspects of pain?
1. Nociceptive receptors
2. Nociceptive activation
3. Sensitization of receptors
4. Nociceptive fibres
131
Describe Nociceptive receptors?
- Free unspecialised nerve endings with ‘pain’ channels inserted in membrane
- Sensitive to O2, pH osmolarity, valinoids (capsicum) & heat
- Allows Ca2+ into cell
132
What is the most common "pain" channels for nociceptive nerves?
Transient Receptor Potential family of channels (TRP)
133
What can nociceptive receptors be sensitised by?
- Substance P
- Bradykinins
- Serotonin
- pH
- ATP
- NO
134
Describe the structure of a nociceptive receptor?
6 unit trans-membrane portion & ‘basket’ of regulatory complex in the cytoplasm
135
Describe the Nociceptive receptor activation due to temperature?
- Extreme heat & cold open ‘Transient receptor potential vanilloid’ (TRPV) channels in membrane
- Na2+ & Ca2+ entry & depolarises cell to give action potential
136
Describe the Nociceptive receptor mechanical activation?
Presumed form of insensitive mechanoreceptor which allows Na entry when activated
137
Describe the Nociceptive receptor chemical activation?
Apart from TRPV receptors, largely unknown but chemical transmission can cause sensitisation of pain receptors
138
What does Calcitonin gene related peptide (CGRP) & SP both do during sensitisation of receptors?
Recruit silent receptors which increase summation in the dorsal horn
139
What does Histamine do during sensitisation of receptors?
Causes hyperalgesia through its effects on blood vessels
140
What does Bradykinin do during sensitisation of receptors?
Activates pain fibres directly & causes increase in prostaglandins
141
What does tissue damage cause?
Produces H ions which give muscle ache (weight lifting)
142
What makes prostaglandin E2 & what drugs inhibit it?
- Made by cyclooxygenase
| - Aspirin & other NSAIDs inhibit enzyme
143
What do neurotransmitters for nociceptive fibres release on stimulation?
- Glutamate
- Substance P
- Calcitonin gene-related peptide (CGRP)
(both central & peripheral synapses)
144
What does peripheral release of nociceptive neurotransmitters give?
Red flare & tenderness associated with pain
145
Substance P & CGRP release is responsible for what 3 local physiological signs of pain?
1. Calor (heat)
2. Rubor (redness)
3. Tumor (swelling)
146
What is color (heat) & rubor (redness) caused by?
Hyperaemia
147
What is tumour (swelling) caused by?
Plasma extravasation
148
Where does pain signal processing begin in?
Dorsal horn (synaptic targets & wind up)
149
What are the 2 types of nociceptive ascending axons from the dorsal horn?
1. Nociceptive specific (NS)- C & Aδ
2. Wide dynamic range neurons (WDR)- any sensory input incl. pain, fire in graded fashion based on C fibre frequency of input (higher pain, higher input)
150
What are the Nociceptive specific (NS) & Wide dynamic range neurons (WDR)?
Points of descending pain modulation from PAG in the brainstem
151
What is "Wind up"?
Long term sensitisation of post synaptic neurons in dorsal horn
152
What is the central sensitisation "wind up" mediated by?
Wide dynamic range neurons (WDR) which, when firing at high frequency, open NMDA channels
153
What does the inrush of Calcium do during central sensitisation "Wind up"?
- Nuclear expression resulting in increased Na channels & blockade of K channels
- Net result is resting potential closer to threshold & more sensitive cell
- Amplifies pain signal
154
What controls the dorsal horn sensitisation "wind up" system?
Intensity of signal from C fibres translated through the WDR neurons into variation in sensitivity
155
Wind up can occur in seconds & last for hrs, this conveys what 3 things?
1. Priority salience in cortex
2. Protection from further injury
3. Memory- increased duration of stimulation increases chance of consolidation
156
What are the 3 parts to pain modulation?
1. Gate theory
2. Sensitisation (wind up)
3. Descending analgesia & Endogenous opioids
157
Describe how the gate theory of pain modulation at the dorsal horn can be damped down?
- By rubbing area around source of pain activates inhibitory input (Aß fibres) to anterolateral system
- Similar theory behind transcutaneous nerve stimulation TENS & capsaicin treatment
158
Describe descending analgesia in pain modulation?
Shows (1) inhibition of incoming pain signals at cord level, (2) encephalin-secreting neurons that suppress pain signals in cord
159
What is the descending analgesia in pain modulation system exploited by?
CNS centers to increase salience of selected signals as well as decrease certain prolonged unimportant signals
160
Give 3 examples of Endogenous opioids? (group of neurotransmitters)
1. Endorphinins
2. Encephalins
3. Dynorphins
161
Describe the endogenous opioid system neurotransmitters?
Sensitive to opiates & present at all levels of pain pathways,
therefore doses of opiates can act simultaneously at all levels, hence their high efficacy
162
Describe the 3 parts of the cortical pain matrix?
1. Somatosensory topographic discrimination
2. Limbic system including the cingulate gyrus & insula- emotional, motivational, modulatory
3. Saliency- relative potentiation of a specific nociceptive input
163
Describe the brainstems purpose in the cortical pain matrix?
- Can up/down modulate nociception to provide saliency (gate system)
- Based on info from other brain centres
164
What does electrical stimulation of the PAG induce?
Strong analgesia (blocked by Nalaxone)
165
List the different types of pain?
- Chronic/Acute
- Nociceptive/ Neuropathic/ Phantom limb
- Maladaptive
Visceral (hollow structures)
- Referred
- Sharp/Ache
- Headache
- Complex regional pain syndrome
166
What usually results in nociceptive pain?
Conditions such as sprains, bone fractures, burns, bumps bruises, inflammation (from infection/arthritic disorder)
167
When does nociceptive pain usually stop?
- When problem is healed
| - Normally responds well to painkillers such as opioids
168
What are the 3 types of chronic pain?
1. Nociceptive pain
2. Neuropathic pain
3. Central maladaption
169
Give 5 examples of persistent neuropathic pain?
1. Causalgia (peripheral nerve trauma)
2. Phantom limb pain
3. Entrapment neuropathy (carpel tunnel syndrome)
4. Peripheral neuropathy (widespread nerve damage
5. Nociceptive pathway damage
170
Give 4 examples of when pain persists beyond the healing process of damaged tissues?
1. Hyperalgesia (strong reaction to low intensity stimuli)
2. Allodynia (painful reaction to non-noxious stimuli like light touch)
3. Summation (repeated low innocuous stimuli increasing intensity of response)
4. Paresthesias (tingling without stim) or Dysesthesias (burning or shooting pain without stim)
171
What causes persistent neuropathic pain?
Maladaptation of the dorsal horn wind up & sensitisation systems
172
What can central maladaption sensitisation lead to?
Long term changes in structure of the synapses in dorsal horn or spinal cord
173
What can increases in inotropic glutamate receptors (NMDA) cause?
Sensitivity in 2nd order neurons which then more readily send pain signals to the thalamus
174
What is a second component of central maladaption?
- Descending modulation of inhibitory interneurons becomes maladapted
- Can lead to reduction in inhibition of WDR neurons & disinhibition of 2nd order neurons
175
What are headaches due to?
Irritation/destruction of sensitive areas around the venous sinuses, dura at the base of the skull or meninges & associated blood capillaries
176
What results in the worst headaches?
Meningitis
177
What does hangovers do?
Caused by excessive drinking, in extreme cases due to alcohol irritating meninges, most cases due to dehydration
178
What does Low CSF cause?
Brain to settle onto base of the skull causing deformation of dura & meninges & so this causes headaches
179
What causes a Migraine?
Possible due to vasoconstriction followed by massive vasodilation, but unproven
180
Describe the mechanism of referred pain?
- Signals of noxious stimuli & normal cutaneous stimuli enter spinal cord at same point
- Cross talk in dorsal horn
- Signals from viscera picked up by ascending nerve fibres that are mapped cortically to dermis
181
Can pain be re-experienced from memory?
- No, it is only an intellectualisation of the experience
| - Fear of pain is very real & important
182
What are the 4 steps to the WHO analgesic ladder?
STEP 1: nonopioid analgesics NSAIDS
STEP 2: weak opioids
STEP 3: strong opioids, methadone, oral administration, transdermal patch
STEP 4: nerve block, epidurals, PCA pump, neurolytic block therapy, spinal stimulators
183
What is the definition of an opium?
- Natural extract of the poppy Papaver somniferum
| - Contains morphine & other related compounds
184
What is the definition of an opioid?
Any substance (natural/synthetic) that produces morphine like effects which are blocked by morphine antagonist
185
What are the 7 different structures/questions for thinking about any drug?
1. What is it? (class of drug)
2. How's it given?
3. It's mechanism of action? (Pharmacodynamics)
4. Main clinical uses?
5. How's it metabolised?
(Pharmacokinetics)
6. Consider effect on each system in turn
7. Should I know anything else about the drug?
186
List 7 strong opioids?
1. Morphine
2. Oxycodone
3. Diamorphine
4. Fentanyl Pethidine
5. Remifentanil
6. Methadone
187
List 4 weak opioids?
1. Codeine
2. Dihydrocodeine
3. Tramadol
4. Loperamide
188
What are 2 antagonists of strong opioids?
1. Naloxone
| 2. Naltrexone
189
What is the oral bioavailability of morphine?
30%
190
What is the oral bioavailability of Oxycodone?
70%
191
What is the oral bioavailability of Fentanyl?
50% (lozenge)
| - very lipophilic so given transdermal
192
What is the oral bioavailability of Codeine?
60%
193
What is the oral bioavailability of Tramadol?
70%
194
What are the 4 different sites of action for opioids? (opioid receptors)
1. mu opioid peptide receptor (MOP)
2. Kappa (KOP)
3. Delta (DOP)
4. Nociception (NOP)
195
What does morphine do at a cellular level?
- Binds to morphine receptors
- Closes Ca2+ channel but enhances the K+
channel which floods out of cell
- Hyperpolarises cell making it less likely to discharge
- Decreases cAMP release preventing neurotransmitter release!
196
What are the systemic actions of opioids?
- Meiosis
- Euphoria
- Depress CVS & RS
- Sedation
- Urticaria, itch
- Stops coughing
- Analgesia
- Constipation & nausea
- Histamine release = bronchospasm
- Urinary retention
- Decrease immunity
197
How are opioids metabolised?
- Prodrugs
- Exceptions
- Active metabolites
- Pharmacogenetics
198
What is the definition of an antagonist?
- Drug with a high affinity for the receptor but no intrinsic activity (Naloxone)
- Naltrexone given to wean addicts off opioids
199
Whats the parenteral & oral doses of Morphine?
1. Parental- 10mg (0.1mg /kg)
| 2. Oral- 30mg (0.3mg/kg)
200
What is the parenteral dose of Fentanyl?
100 micrograms
201
What are the 3 guidelines for prescribing opioids?
1. Controlled Drugs
2. Misuse of Drugs Act, 1971 classified according to the “harmfulness attributable to a drug when it is misused”
3. Misuse of Drugs Regulations 2001
202
What happens when you increase the dose of a weak opioid?
Have a "ceiling effect" where escalation of dose causes side effects without improving analgesia
203
What is the functions of pain?
- Unpleasant therefore alerts us to potential damage of body
| - Signal onset of disease --> help-seeking behaviour
204
What happens to people with congenital universal insensitivity to pain (CUIP)?
Usually die at young age because failing to respond to illnesses of which the main symptom is pain (appendicitis) or avoid situations that risk their health
205
What happens if pain continues?
Becomes destructive & problematic
206
What are the 3 different types of chronic pain?
1. Chronic recurrent pain
2. Chronic benign pain
3. Chronic progressive pain
207
Describe acute pain?
- Often result of some specific & readily identifiable tissue damage (a broken leg, surgical lesion, toothache)
- Less than 3-6 months
- Pain disappears once damaged tissue healed
208
When can we classify pain as being Chronic?
- More than 3-6 months
- Starts with episode of acute pain but doesn’t improve
- Can have identifiable cause (rheumatoid arthritis) or unidentifiable (most back pains)
209
Describe Chronic recurrent pain?
Repeated, intense episodes of pain separated by periods without pain (migraine, myofascial pain)
210
Describe Chronic benign pain?
Long-term pain that is typically present all of the time, with varying levels of intensity (chronic low back pain)
211
Describe Chronic progressive pain?
Pain becomes progressively worse as the underlying condition worsens (rheumatoid arthritis)
212
What is the Specificity theory of biological models of pain?
- Pain receptors in skin when activated transmit info to centre in brain that processes pain-related info
- Sensation of pain is a direct representation of degree of physical damage experienced by the individual
213
When/Who proposed the Specificity theory?
1st proposed in 3BC by
| Epicurus & taken up by Descartes in 17th C
214
Give an example of when we experience pain in the absence of pain receptors?
Phantom limb pain
215
Give an example of "pain receptors" that do not transmit pain?
Congenital universal insensitivity to pain (CUIP)
216
Give an example of psychological influences on pain?
- Mood, attention, cognitive factors (e.g, expectations)
| - Depressed/anxious people report the equivalent pain stimulus as more painful than people who are not
217
Who developed the Gate control theory for pain?
Melzack & Wall (1965)
218
Describe the Gate control theory for pain?
- 'Gate’ used as metaphor for the chemicals, including endorphins, that mitigate the experience of pain
- Account both the sensory info & the psychological processes
- Pain as a perception rather than sensation
219
Describe the relationship of attention and pain?
Focusing on pain increases its impact & focusing on other things seems to reduce it (bed rest is no longer treatment for back pain)
220
What did James & Hardardottir (2002) do to research attention & pain?
- Participants put their lower arm in cold water (0-3C, cold pressor test) & to concentrate on computer-based task or the pain sensations
- Those focused on pain were least able to tolerate the pain
221
What can attentional bias explain?
Why some people with acute pain develop chronic pain in the absence of physical injury/inflammation
222
What are 3 types of cognition & pain?
1. Meaning of pain ie. childbirth
2. Catastrophizing
3. Expectations of pain relief (placebo)
223
What are the 3 components of catastrophizing & experiencing pain?
1. Rumination- focus on internal & external info
2. Magnification- overestimating extent of threat
3. Helplessness- underestimating resources.
224
Describe the effects of living with chronic pain?
- Organise day around pain
- Social, financial & physical
- Anger, fear, sadness
- Depression levels high
225
What is the prevalence rates for major depression in 1. pain clinics/inpatient pain programmes, 2. orthopaedic/ rheumatology clinics?
1. 52%
| 2. 56%
226
Why is depression levels higher in chronic pain patients?
- Focusing on bodily symptoms more & reporting pain symptoms
- Pain --> strain of living with pain & restrictions on life depression
- Reciprocal relationship between depression & pain
227
What are 4 different pain behaviours?
1. Facial/audible expression (clenched teeth & moaning)
2. Distorted posture/ movement (limping, protecting the pain area)
3. Negative emotions (irritability, depression)
4. Avoidance of activity (not going to work, lying
down)
228
Describe the 3 "gains" associated with pain?
1. Primary (intrapersonal)- expression results in reduction/cessation of aversive consequence (someone taking over a household chore)
2. Secondary (interpersonal)- pain behaviour gives positive outcome (sympathy/ care)
3. Tertiary- pleasure/ satisfaction of person who is helping the pain sufferer
229
What are the 5 D's?
1. Dramatization of complaints
2. Disuse through inactivity
3. Drug misuse as result of over-medication
4. Dependency on others due to learned helplessness & impaired use of coping skills
5. Disability due to inactivity
230
Describe what good social support is for pain sufferers?
Discouraging avoidance of physical & social activities, offering assistance by multiple solutions to problems & providing emotional support
231
What is the management for acute pain?
Usually pharmacological interventions
232
What is the management for chronic pain?
Psychological approaches to minimise amount of painkiller & maintain/improve quality of life
233
What are the 2 different easy to administer techniques for measuring pain?
1. Numerical rating scales- 0 (no pain) to 100
(most pain you could imagine)
2. Descriptive adjectives- mild, distressing, excruciating
234
Describe the 4 parts to the McGill pain questionnaire?
| more difficult to administer but captures the multidimensional nature
1. Type of pain- throbbing, shooting, hot, tender, etc
using a 4-point scale
2. Emotional responses- tiring, fearful, punishing
3. Intensity of pain- ‘no pain’ to ‘worst possible pain’
4. Timing of pain- brief, continuous or intermittent
235
What are 4 other things to remember when assessing other aspects of pain (Turk & Okifuji)?
1. Verbal/vocalisations (sighs, moans)
2. Motor behaviour (limping, facial grimacing)
3. Taking medication (use of cane)
4. Functional limitations (resting, reduced activity)
236
What is behavioural interventions (Fordyce 1976) based on?
Operant conditioning processes
237
What are the 3 methods for behavioural interventions?
1. Reinforcement of adaptive behaviours
2. Withdrawal of attention/ other rewards that were previous responses to pain behaviour
3. Providing analgesic medication at set times rather than in response to behaviour
238
What are the 3 goals of cognitive-behavioural interventions?
1. Alter beliefs that their problems are manageable
2. Identify how catastrophic/ other negative thoughts can lead to increased pain, distress & psychosocial difficulties
3. Strategies to manage pain, emotional distress & psychosocial difficulties
239
Describe the use of relaxation for pain management?
- Relax whole body/specific muscle groups
- Systematic & methodical approach to learning deep muscle relaxation
- Controlled breathing, from short/shallow breathing to deeper/longer breaths
240
What is biofeedback?
- Control of bodily processes
- EMG, galvanic skin response
- Guided by auditory/visual feedback on physiological changes
- Relax muscle tension
- Used successfully with chronic headaches
241
What 2 things detect static tilt & translation?
1. Saccule (vertical movement)
| 2. Utricle (horizontal movement)
242
What detects rotational acceleration (pitch roll & yaw)?
Semi-circular canals
243
What are the 2 otolith containing organs in the vestibule?
1. Saccule macula (continuous with cochlea)
| 2. Utricle macula (continuous with semi-circular canals)
244
Where do hair cells project hairs into?
Otolithic (ear stone) containing gelatinous structure
245
What does cilia + kinocilium provide?
Directional information
246
What does movement of otolithic membrane (tilting/translational movement) do?
Bends cilia/kinocilium in a very direction specific way
247
What opens/closes hair cell cation channels?
0.5micron movement of kinocillium
248
What are the 2 orientations of the hair cells in the ventricle?
Vertical & horizontal (when head is normally held upright)
249
What is the base of hair cells supported by?
Area of supporting cells called the macula
250
What are fat ends & thin ends?
- FAT: kinocillia
| - THIN: steriocillia
251
What happens when hairs are bent away from kinocillium?
- Hyperpolarisation
- Decreased impulse frequency
- Inhibition
252
What happens when hairs are bent towards the kinocillium?
- Depolarisation
- Increased impulse frequency
- Excitation
253
What do we also monitor for a better triangulation of movement?
Rotational movement
254
Describe how semi-circular canals monitor rotational acceleration & deceleration?
- 3 planes of orientation (yaw, roll, pitch)
- Within each canal is semi-circular duct
- Within duct, ampulla
255
What does the ampulla have within?
Supporting cells, hair cells, cilia & kinocilium
256
What causes movement of cupola?
Endolymph in semi-circular canal
257
What does dynamic equilibrium measure?
Changes in rotation
258
Describe how dynamic equilibrium measures changes in rotation?
- Signal transduction
- Resting rate of transmitter release
- Bending towards the kinocilium ↑AP rate
- Bending in other direction ↓AP rate
259
What is the vestibular apparatus bathed in?
Endolymph
260
How is the vestibular apparatus endolymph usually drained?
To venous sinus
261
What causes Ménière’s disease?
Build-up of endolymph (blockage of venous sinus) causing vertigo, nausea, tinnitus & hearing loss
262
Where does information from the vestibular apparatus go?
To cerebellum & brainstem (integrated with other info)
263
What is the 3 vestibular apparatus functions?
1. Control eye muscles (oculomotor nerve)
2. Maintain an upright position (spinal motor nuclei)
3. Aware of body position & acceleration
264
What does the caloric test in comatose patients test for?
Condition of brainstem
265
Describe the caloric test?
- Putting warm water in external meatus mimics moving head towards the irrigated ear
- Cold water does the opposite
266
What Particular plane is the caloric test done in?
Supine patient with head at 30 degrees from horizontal mimics left/right movement of head
267
What is the nystagmus pattern for a movement?
Towards irrigated ear is slow away from direction of rotation & fast return in same direction
268
What does the caloric test show in comatose patients?
No fast saccade, only slow component
269
What would be shown in the caloric test if the vestibular nucleus is undamaged?
Cold irrigation (mimics head being turned away from irrigation) will cause slow movement towards the irrigated ear
270
When does spontaneous nystagmus occur?
When 1 side of the patients system has damage to 1 of the semi-circular canals, there is a difference between 2 signals when the head is stationary
271
What are the 2 steps when putting warm water in the external acoustic meatus?
1. Endolymph rises
| 2. Increased firing
272
What are the 2 steps when putting cold water in the external acoustic meatus?
1. Endolymph falls
| 2. Decreased firing
MD4001
flashcards
Decks in class (11)
# Cards
