1. Somatosensory perception: Touch, pain and analgesia
Lecture 2
Somatosensory perception:
Touch, pain and analgesia

2. Somatosensory perception
Peripheral
Sensory receptors
Spinal cord
Brainstem
Thalamus
Somatosensory cortex
Other cortical areas
Cingulate cortex
Cranial

3. Peripheral sensory receptors
Free nerve endings
(pain, temperature)
Merkel’s disc (touch)
Meissner’s corpuscle (touch)
Pacinian corpuscle (vibration)
Ruffini’s ending (stretch)
Hair follicle receptor
Converts mechanical energy to electrical energy
Spinal cord
Labelled
lines

5. Nociception Nociception –the perception of a noxious stimulus
Pain – the subjective ‘feeling’ due to a noxious stimulus
Analgesia – the modulation of nociception or pain
Transduction of a noxious stimulus into electrical activity in appropriate nerve endings
Transmission of the electrical signal through nerves, to the spinal cord and the brain
Perception of the noxious stimulus in brain areas, and the conscious ‘feeling’ of pain
Modulation of signal at various levels (analgesia)

6. Levels of nociception Transduction
Noxious stimuli activate peripheral nociceptors
Mostly polymodal, responding to mechanical, thermal and chemical stimuli
Some unimodal
Responses mediated through histamine, prostoglandins, bradykinin etc.
Peripheral transmission
Peripheral nociceptive fibres enter spinal cord through the dorsal root and terminate in the dorsal horn
Synapse in the dorsal horn with both ascending axons and spinal interneurones
Neurotransmitters at the spinal cord: glutamate and substance P

7. Central transmission
Ascending axons cross midline and ascend through anteroelateral column of the spinal cord
Terminate in the ventral posterior nucleus of the thalamus
Collateral terminations in the brain stem
Projections from brainstem to thalamus
Thalamus projects to somatosensory cortex
Also to cingulate cortex
Reciprocal connections between somatosensory and cingulate cortices.
Figures from :
Carlson: Physiology of Behaviour

9. ‘Pain’ perception
Perception of pain is probably in the cingulate cortex
Cingulate cortex is activated in people during illusory pain
Pain is a subjective experience based on the information received from nociceptive fibres
The brain can be fooled into thinking something is painful, even though no tissue damage has occurred
Mechanism of pain perception is very poorly understood

10. Opium and opioid drugs
Opium is one of the earliest known drugs used by man
Comprises the dried sap of the opium poppy
Sedative and analgesic
Well known to ancient Greeks
Two main active components of opium
Morphine (~10%)
Codeine (~0.5%)
Morphine is poorly absorbed orally.
Hence, to produce central effects, it is injected.
Other opioid drugs.
Heroin, methadone.

11. Morphine
Morphine acts through binding sites in the brain and spinal cord
What are the endogenous receptors which morphine acts on?
At first believed to act as an antagonist at one or more stages of the pain pathway
But effects of morphine are blocked by naloxone
Suggests that morphine is an agonist not an antagonist
Morphine is not endogenous
Endogenous opioids were isolated in 1970s
Enkephalins, endorphins, dynorphins

12. Opioid Analgesia
Morphine injected into lateral ventricles relieves severe pain
effective at doses 10-fold lower that for systemic injection
therefore acting in the brain
Intracerebral injection of morphine induces analgesia
periaqueductal grey matter (PAG)
periventricular grey matter (PVG)
rostroventral medulla (RVM)
These effects are blocked by naloxone
Naloxone injected into PAG, PVG or RVM partially reverses analgesic action of systemically administered morphine

13. Stimulation Produced Analgesia
Electrical stimulation of localised brain areas suppress pain perception
periaqueductal grey matter (PAG)
periventricular grey matter (PVG)
rostroventral medulla (RVM)
Analgesia is an active process
How does stimulation produced analgesia relate to opioid analgesia?

14. Similarities between opiate analgesia and stimulation produced analgesia
Effective loci are the same in each case (i.e. PAG, PVG, RVM)
Both are blocked by naloxone
Combining sub-analgesic levels of both produces analgesia
Cross-tolerance develops between the two.
Both effects cause blockade of spinal reflexes
therefore mediated at the level of the spinal cord
Both effects activate the same descending spinal pathway
dorsolateral funiculus
Therefore stimulus produced analgesia is mediated through opioid mechanisms

15. Levels of opiate analgesia
Supraspinal
opioid receptor activation in brain stem
mediated via spinal cord mechanisms
mu-receptor mediated (i.e. enkephalins)
Spinal
opoid receptors activation in spinal cord
delta- & kappa- receptor mediated (enkephalins & dynorphins)
Hormonal
stress-induced analgesia is reversed by naloxone
also reversed by removal of adrenal glands
mechanism is unclear

16. Non-opiate analgesia Brain stem
Noradrenaline and 5HT modulate analgesia
Especially in PAG and PVG
Mechanism not clearly understood
Spinal cord
Noradrenaline injected into spinal cord blocks responses to noxious stimuli
5HT injected into spinal cord is analgesic
blocks spinal cord nociceptive neurones
blocks spino-thalamic neurones

17. Ascending nociceptive pathway
Control of analgesia
(+)
(+)
(+)
Morphine/SPA
Central grey matter
(+)
(+)
Raphe
nuclei
Rostroventral
medulla
Ascending nociceptive pathway
(+) Na
5HT
(-)
(-)
Nociceptive neurone
Enk
(-)
(+)

18. Alternative methods of analgesia
Transcutaneous electrical nerve stimulation (TENS):
Alters nociceptive signal to brain, or brain’s perception of pain
Mechanism unclear but may activate endogenous opiate systems
Acupuncture
Greater than 80% increase in pain threshold
Increased enkephalin levels in the brain
Increased biosynthesis of enkephalins
Effects were enhanced by enkephalinase inhibitors
May be mediated via enkephalin release in PAG and PVG
Placebo : may activate endogenous pain-control systems
Hypnosis : alters brains perception of pain
Stress : both opiate and non-opiate mechanisms
Cognitive : may activate endogenous pain-control systems

19. Summary
Sensory perception occurs at peripheral modality-specific receptors
Information transmitted to the brain through cranial or spinal nerves
Makes connections in brainstem and thalamus
Information enters cortex at unimodal primary sensory cortices
Hierarchical processing occurs in unimodal association cortices
Highly processed unimodal signals enter multimodal association cortex, where sensory integration occurs