Lecture 2

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

2. Somatosensory perception Peripheral Sensory receptors 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. Thalamus projects to somatosensory cortex • Also to cingulate cortex • Reciprocal connections between somatosensory and cingulate cortices. 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 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 partiallyreverses 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 • dorsolateralfuniculus 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 nociceptiveneurones • blocks spino-thalamic neurones

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

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