Nociception, pain and analgesia

Question 1

What is meant by Haptic perception?

Answer 1

Many systems interacting i.e. sensory (detecting touch, temp etc), motor (movement of fingers and hands), and cognitive (integrating info provided by sensory and motor and holding that in memory)

Question 2

What are the 4 exploratory procedures of haptic perception?

Answer 2

Lateral motion - texture
Pressure - texture (deformable or not)
Enclosure - shape
Contour following - shape

Question 3

How do our mechanoreceptors allow us to perceive the shape of something?

Answer 3

Object stimulates multiple mechanoreceptors at once
Receptor at contact point responds most, and signal lessens with distance - tells brain about object curvature
The larger the object, the more diffuse the area of contact activation, skin deformation covers a larger area so slow-adapting fibres less responsive

Question 4

What are the stages of somatosensory perception?

Answer 4

Peripheral sensory receptors transmit to spinal cord and from there to brainstem
Cranial sensory receptors transmit directly to brainstem
From brainstem fibres travel to thalamus –> somatosensory cortex –> cingulate cortex and other cortical areas

Question 5

Why is it important for us to be able to feel physical stimuli?

Answer 5

Feedback from objects - ability to grasp objects appropriately
Proprioception and body position
Warning and protection - e.g. need to move hand from hot surface

Question 6

What are the 2 types of slowly adapting mechanoreceptors?

Answer 6

Ruffini cylinders - fire continuously (activate when pressure applied and fire until stimulus removed but lessen with time), perception of stretching, deep in skin with large receptive field
Merkel receptors - fire continuously, sense fine spatial details, near epidermis with small receptive field, highest density in finger tips

Question 7

What are the 2 rapidly acting mechanoreceptors?

Answer 7

Pacinian corpuscle - fires to on and off, perceive vibration, pressure and fine texture, deep in skin with large receptive field, respond poorly to continuous pressure but well to high rates of vibration (i.e. responds best to stimulation CHANGE)
Meissner Corpuscle - fires for stimulus on and off, hand grip control and light touch, near epidermis with small receptive field

Question 8

What does Katz’s duplex theory suggest?

Answer 8

Perception depends on how a surface is explored:
Spatial cues - e.g. bumps
Temporal cues - as skin moves across texture we get information in the form of vibrations

Question 9

What are the two main sensory pathways from skin to brain?

Answer 9

Medial Lemniscal - signals representing proprioception and touch, high speed and important for movements in response to touch
Spinothalmic - Signals responding to pain and temperature
Both pathways cross over to contralateral hemisphere on way to thalamus, and then to somatosensory receiving area (S1, parietal)
Signals also travel between S1 and S2 (secondary somatosensory cortex) and other somatosensory areas

Question 10

What is meant by experience-dependent plasticity?

Answer 10

corresponding area of S1 increases with use e.g. musicians of stringed instruments will develop increased cortical representation for left hand

Question 11

What are the 3 types of pain?

Answer 11

Nociceptive - activation of nociceptors in skin (different types for different stimuli)
Inflammatory - Damage to tissues e.g. by tumour cells
Neuropathic - Lesions or other damage to components of the nervous system e.g. carpal tunnel

Question 12

What three factors can influence pain aside from simple skin stimulation, according to gate control theory?

Answer 12

Mental state - pain perceived less if confers positive aspect e.g. escape
Phantom limb - Suggests pain originates in brain rather than skin
Attention - Pain can increase when you realise you are injured and draw attention to the area

Question 13

What does the gate control theory suggest?

Answer 13

Pain signals enter spinal cord from body and travel to brain, while additional pathways influence this signal from spinal cord to brain - signals from these can act to open or close the gate in the spinal cord determining strength of signal actually reaching brain

Question 14

What have fMRI scans shown in relation to hypnosis and pain?

Answer 14

Similarity between physically and hypnotically induced brain activation, with overlap in the thalamus, anterior cingulate cortex, insula, parietal cortex and prefrontal cortex - clear connection between brain activation and pain experience, and idea of distributed representation in brain

Question 15

What are the 2 components of pain?

Answer 15

Sensory - served by the primary somatosensory receiving area; hypnosis to decrease subjective intensity (Sensory) changed perception of both intensity and unpleasantness (emotional), accompanied by changes in S1
Emotional (e.g. annoying pain) - anterior cingulate cortex, suggestion to reduce unpleasantness didn’t affect intensity and only changes in ACC not S1; so ACC important for unpleasantness of pain, and this can change even when intensity is the same

Question 16

What is naloxone?

Answer 16

Similar structure to opiates and endorphins so can bind to opioid receptors and revive someone from heroin overdose (but blocking these receptors also increases pain)

Question 17

What are pain thresholds?

Answer 17

different individuals have genetic differences in amount of opioids released in response to painful stimuli
More opioids released, higher pain threshold

Question 18

What is pain of social loss like?

Answer 18

Activates some of the same areas as physical pain - feelings of being ignored or excluded for example can activate the ACC, and activation is greater when reported distress is greater

So shared physiological pain mechanisms even when stimulation is different

Question 19

What happens at rest in the brainstem?

Answer 19

There is tonic inhibition of periaqueductal gray and periventricular gray by GABA neurons - glutamate fibres are inhibited

Question 20

What happens when an excitatory nociceptive signal from the periphery arrives at the spinal cord?

Answer 20

Activates the ascending excitatory pathway to the thalamus, PAG/PVG and Locus Coeruleus - we see ascending activation of enkephalinergic interneurone via glutamate, which has an inhibitory action on the GABA neurones, switching off their tonic inhibition
Descending glutamate neurones now activated and fibres activate descending serotonergic (raphe nuclei) and noradrenergic (locus coeruleus) fibres –> inhibit spinal cord activity (noradrenaline released by both direct and indirect action)

Question 21

How do serotonin and noradrenaline inhibit the spinal cord?

Answer 21

Noradrenaline inhibits spinal cord directly
Serotonin inhibits by activating inhibitory encephalin interneurons within the spinal cord which then inhibits cord activity (serotonin itself is excitatory)

Question 22

What is the impact of morphine on brainstem mechanisms of analgesia?

Answer 22

Mimics activation of encephalin neurones, inhibiting GABA neurones and disinhibiting the descending glutamate fibres

Question 23

What is the impact of electrical stimulation?

Answer 23

Activates excitatory input and encephalin interneurone, inhibiting GABA neurone and disinhibiting descending Glutamate fibres

Question 24

What is meant by labelled lines?

Answer 24

Fibres from each mechanoreceptor and their information travel to spinal cord separately and in parallel, integration does not happen at level of skin
Primarily the job of A-alpha fibres (very fast)

Question 25

How do A-alpha and A-beta fibres play a role in spinal cord analgesia?

Answer 25

Activation of somatosensory pathways inhibits nociceptive pathways via an interneurone

Question 26

What is the difference between nociception and pain?

Answer 26

Nociception is the objective and measurable perception of a noxious stimulus
Pain is the subjective “feeling” resulting from a noxious stimulus, variable between individuals and at different times, and can be experienced in the absence of nociception

Question 27

What is the first stage of nociception?

Answer 27

Transduction - of the noxious stimulus into electrical activity
Stimulus activates peripheral nociceptors, most of which are POLYMODAL i.e. respond to mechanical, thermal and chemical stimuli
Responses to this activation i.e. skin reddening etc. are mediated through HISTAMINE, PROSTAGLANDINS, BRADYKININ etc

Question 28

How is the nociceptive signal transmitted to the spinal cord and brain?

Answer 28

Peripheral nociceptive fibres enter spinal cord through the DORSAL ROOT along with peripheral somatosensory fibres, terminating in the DORSAL HORN
Synapse in dorsal horn with both ascending axons and spinal interneurons (which remain in that locality and modulate signals coming in)
NTs at spinal cord are GLUTAMATE and SUBSTANCE P

Question 29

What do the ascending axons do?

Answer 29

Cross the midline and ascend through the ANTEROLATERAL COLUMN of the spinal cord –> mechanoreceptor pathways cross over at a different level, usually within the medulla
These fibres terminate at the thalamus, with some collateral terminations in the brain stem too

Question 30

Where does the thalamus project to?

Answer 30

The somatosensory cortex and cingulate cortex (area for subjective experience of pain, activated during “imagined” pain)
There are reciprocal connections between the somatosensory and cingulate cortices i.e. backwards and forwards

Question 31

How can opioid analgesia modulate these signals?

Answer 31

Opium has both sedative and analgesic effects, its main components being morphine and codeine - morphine absorbs poorly orally so needs to be injected to have central effects
Acts through binding sites in brain and spinal cord - initially thought to be an antagonist i.e. blocking receptors and transmission, but effects of morphine are blocked by naloxone which is a universal opiate antagonist, suggesting morphine is actually an agonist, activating rather than blocking receptors

Question 32

What happens when morphine is injected into lateral ventricles?

Answer 32

Relieves severe pain, 10 times more potent than a systemic injection outside of CNS

Question 33

Which brain areas are sensitive to intracerebral microinjections of morphine?

Answer 33

PAG - surrounds cerebral aqueduct between third and fourth ventricles
PVG - extension of PAG further back in pons
Rostroventral medulla

Question 34

What happens if morphine is injected systemically, and naloxone is then injected into one of the three sensitive areas?

Answer 34

We get partial reversal of the analgesic effect - tells us that morphine is acting centrally, but also working elsewhere in body and these non-central effects are not reduced by centrally-administered naloxone

Question 35

What are examples of endogenous opioids?

Answer 35

Enkephalins, endorphins, and dynorphins
All act on different receptor types but all blocked by naloxone

Mu receptors - sensitive to morphine and endorphins
Delta receptors - sensitive to enkephalins
Kappa receptors - sensitive to dynorphins

Question 36

What is meant by stimulation-produced analgesia?

Answer 36

Electrical stimulation of the endogenous analgesic systems (same 3 localised brain areas) can also suppress pain perception, implying that analgesia is an active process not simply passive blocking of signals

Question 37

What are the key similarities between stimulation-produced and opioid analgesia?

Answer 37

Effective loci are the same three
Both blocked by naloxone
Combining sub-analgesic levels of both produces analgesia (additive effects indicates work on same pathways)
Cross-tolerance develops between the two - tolerance for one leads to tolerance for the other
Both block spinal reflexes, indicating mediation at level of spinal cord
Both activate same descending pathways

Question 38

On what three levels does opioid analgesia such as morphine work?

Answer 38

Supraspinal - Opioid receptor activation in the brainstem mediated by spinal cord mechanisms (mu-receptor mediated i.e. endorphins)
Spinal - Opioid receptor activation in spinal cord (kappa and delta receptor mediated i.e. enkephalins and dynorphins)
Hormonal - Stress induced analgesia can be reversed using naloxone and by removal of adrenal glands (opioids potentially released from here)

Question 39

What are the 3 levels of non-opioid analgesia?

Answer 39

Brainstem - NA and 5HT modulate analgesia in PAG and PVG
Spinal cord - NA injected into spinal cord blocks responses to noxious stimuli, while 5HT when injected blocks spinal cord nociceptive neurons and blocks spinothalmic neurons
Periphery - Anti-histamines and anti-inflammatories reduce impact of injury, while local anaesthetics reduce transmission of signal

Question 40

What are 5 alternative methods of analgesia aside from morphine and stimulus-produced analgesia?

Answer 40

TENS (transcutaneous electrical nerve stimulation) - alters nociceptive signal to brain or brain’s perception of pain through activation of a-alpha and beta fibres of the somatosensory system (gate-control - activate inhibitory neuron which inhibits projection neuron activated by c fibres, limiting transmission of pain signals to sensory cortex)
Acupuncture - produces >80% increase in pain thresholds through increasing encephalin levels in the brain (increasing biosynthesis of encephalins and subsequent release in PAG and PVG
Placebos - may activate endogenous pain control systems
Hypnosis - alters brain perception of pain at cortical level
Stress - both opiate and non-opiate mechanisms