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Md surg pain 2013


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  • 1. Physiology of pain Prof. Vajira Weerasinghe Professor of Physiology, Faculty of MedicineUniversity of Peradeniya & Consultant Neurophysiologist, Teaching Hospital, Peradeniya
  • 2. Topics covered in the lecture1. What is pain (International definition of pain)2. Dual nature of pain: fast pain and slow pain3. What causes pain : pain stimuli4. Nerve pathways carrying pain signals to the brain5. Brain areas involved in pain perception6. Pain modulatory pathways7. Neurochemicals involved in pain pathways
  • 3. What is pain?• Pain is a difficult word to define• Patients use different words to describe pain• eg.• Aching, Pins and needles, Annoying, Pricking, Biting, Hurting, Radiating, Blunt, Intermittent, Burning, Sore, Miserable, Splitting, Cutting, Nagging, Stabbing, Crawling, Stinging, Crushing, Tender, Dragging, Numbness, Throbbing, Dull, Overwhelming, Tingling, Electric-shock like, Penetrating, Tiring, Excruciating, Piercing, Unbearable• Different words in Sinhala or in Tamil
  • 4. What is pain?• There is an International definition of pain formulated by the IASP (International Association for the study of pain)• Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage IASP – International Association for the Study of Pain 2011
  • 5. definition of pain• It is a symptom• Associated signs are crying, sweating, increased heart rate, blood pressure, behavioural changes• It is difficult to describe pain although we know what it is• It is difficult to measure pain – visual analogue scale is used• It is a complex sensory modality essential for survival
  • 6. Different situations•No stimuli, but pain is felt •phantom limb pain •eg. in amputated limb•Stimuli present, but no pain felt •eg. soldier in battle field, sportsman in arena•Pain due to a stimulus thatdoes not normally provoke pain •Allodynia•Pain caused by a lesion or disease of thesomatosensory nervous system •Neuropathic pain
  • 7. Pain terminology International Association for the Study of Pain 2011• Paresthesia – An abnormal sensation, whether spontaneous or evoked• Dysesthesia – An unpleasant abnormal sensation, whether spontaneous or evoked• Hyperalgesia – Increased pain from a stimulus that normally provokes pain• Allodynia – Pain due to a stimulus that does not normally provoke pain• Hyperesthesia – Increased sensitivity to stimulation, excluding the special senses (increased cutaneous sensibility to thermal sensation without pain )• Hyperalgesia – Increased pain from a stimulus that normally provokes pain• Causalgia – A syndrome of sustained burning pain, allodynia, and hyperpathia after a traumatic nerve lesion, often combined with vasomotor and sudomotor dysfunction and later trophic changes• Hyperpathia – a painful syndrome characterized by an abnormally painful reaction to a stimulus, especially a repetitive stimulus, as well as an increased threshold• Neuralgia – Pain in the distribution of a nerve or nerves
  • 8. Pain terminology International Association for the Study of Pain 2011• Neuropathic Pain – Pain caused by a lesion or disease of the somatosensory nervous system• Nociceptive pain – Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors• Neuropathy – A disturbance of function or pathological change in a nerve: in one nerve, mononeuropathy; in several nerves, mononeuropathy multiplex; if diffuse and bilateral, polyneuropathy• Nociception – The neural process of encoding noxious stimuli• Noxious stimulus – A stimulus that is damaging or threatens damage to normal tissues.• Pain threshold – The minimum intensity of a stimulus that is perceived as painful.
  • 9. • Transduction – Process of converting noxious stimulus to action potentials• Perception – Central processing of nociceptive impulses in order to interpret pain
  • 10. Dual nature of pain fast and slow pain• fast pain • slow pain – acute – chronic – pricking type – throbbing type – well localised – poorly localised – short duration – long duration – Aδ fibres are involved – unmyelinated C fibres are – fast conduction 20 m/s involved – somatic pain – slow conduction 1-2 m/s – visceral pain
  • 11. • Physical Stimuli – pressure etc• Electrical• Thermal – cold, hot• Chemical – H+, lactic acid, K+, histamine, bradykinin, acetylcholine, proteolytic enzymes – Prostaglandins • these increase the sensitivity (decrease the threshold) for other nociceptive stimuli
  • 12. receptors• there are no specialised receptors• free nerve endings are sensitive to pain stimuli• free nerve endings are distributed everywhere • both somatic and visceral tissues • except brain tissue and lung parenchyma• nociceptors are very slowly adapting type• different types of nociceptors – some respond to one stimulus – some respond to many stimuli (polymodal) – some may not respond to the standard stimuli (silent nociceptors), they respond only when inflammatory substances are present• TRPV1 receptor (capsaicin receptor) – respond to capsaicin, heat, low pH – stimulation leads to painful, burning sensation
  • 13. central connections• afferent fibre enters the spinal cord • synapses in laminae I and II (substantia gelatinosa) • visceral fibres have more diffused distribution (I,V,X) – (Large Ab fibres termiate in laminae layers III to V)substantiagelatinosa Neurotransmitter at the first synapse of the pain pathway is substance P
  • 14. ascending pathway• crosses the midline• ascends up as the lateral spinothalamic tract• pain originating from head and neck region travel through trigeminal nerve, trigeminal nucleus and supply thalmus• spontaneous firing of trigeminal pathway may result in “trigeminal neuralgia” Pain C fibre lateral spinothalamic tract substantia gelatinosa
  • 15. se nthalamocortical so rtracts yc or te x thalamus lateral spinothalamic tract C fibre
  • 16. Pain perception• This occurs at different levels – thalamus is an important centre of pain perception • lesions of thalamus produces severe type of pain known as ‘thalamic pain’ – Sensory cortex is necessary for the localisation of pain – Other areas are also important • reticular formation, limbic areas, hypothalamus and other subcortical areas
  • 17. Pathophysiology of pain• Pain sensations could arise due to – Inflammation of the nerves (neuritis) – Injury to the nerves and nerve endings with scar formation (disk prolapse) – Injury to the structures in the spinal cord, thalamus or cortical areas that process pain information (spinal trauma) – Abnormal activity in the nerve circuits that is perceived as pain (phantom limb pain) – Nerve invasion, for example by cancer (brachial plexopathy)
  • 18. Descending pain modulatory system• several lines of experimental evidence show the presence of descending pain modulatory system – discovery of morphine receptors – they were known to be present in the brain stem areas – discovery of endogenous opioid peptides • eg. Endorphines, enkephalins, dynorphin
  • 19. opioid peptides• short peptides originally known to be secreted in CNS and later found to be present in GIT etc
  • 20. opioid peptides∀ β endorphin • Earliest to discover, present in pituitary• encephalins - met & leu • widely distributed• dynorphin• Endomorphine 1 & 2• PronociceptinsNaloxone is an opioid antagonist. It blocks the actions of opioidReceptors: mu, kappa, delta, recently discovered ORL1 receptor
  • 21. • descending tracts involving opioid peptides as neurotransmitter were discovered• these were known to modify (inhibit) pain impulse transmission at the first synapse at the substantia gelatinosa
  • 22. • first tract was discovered in 1981 by Fields and Basbaum – it involves enkephalin secreting neurons in the reticular formation – starting from the PAG (periaqueductal grey area) of the midbrain – ending in the NRM (nucleus raphe magnus) of the medulla – from their ending in the substantia gelatinosa of the dorsal horn
  • 23. periaqueductal grey nucleusmidbrain pons nucleus raphe magnusmedulla spinal cord substantia gelatinosa
  • 24. • in the subtantia gelatinosa – enkephalin secreting neuron is involved in presynaptic inhibition of the pain impulse transmission by blocking substance P release
  • 25. substantia descending inhibitory tract gelatinosa dorsal hornc fibre input substantia gelatinosa cell
  • 26. Presynaptic inhibition enkephalin substance P
  • 27. Presynaptic inhibition enkephalin substance P blocking of pain impulse pain impulse
  • 28. • since then various other descending tracts were discovered• all of them share following common features – involved in brain stem reticular areas – enkephalins act as neurotransmitters at least in some synapses – most of these tracts are inhibitory – midbrain nuclei are receiving inputs from various areas in the cortex, subcortical areas, limbic system, hypothalamus etc – the ascending tract gives feedback input to the descending tracts – recently even nonopioid peptides are known to be involved
  • 29. • final pain perception depends on activity of the – ascending pain impulse transmitting tracts – descending pain modulatory (inhibitory) tracts
  • 30. se nthalamocortical so rtracts yc or te x thalamus lateral spinothalamic tract C fibre
  • 31. Intensity theory Specificity theoryTheories of pain touch pain touch pain There is a single pathway for touch There are two and pain different Less intensity produces touch pathways for Increased intensity produces pain touch and pain
  • 32. Gate control theory• This explains how pain can be relieved very quickly by a neural mechanism• First described by P.D. Wall & Melzack (1965)• “There is an interaction between pain fibres and touch fibre input at the spinal cord level in the form of a ‘gating mechanism’
  • 33. Gate control theory central controltouchAβ fibre transmission cellpainC & Aδfibres
  • 34. Gate control theory pain is felt central control touch Aβ fibre transmission cell + pain gate is C & Aδ opened fibreswhen C fibre is stimulated, gate will be opened & pain is felt
  • 35. Gate control theory pain is central control not felt touch Aβ fibre transmission + - cell pain gate is C & Aδ closed fibreswhen Aβ & C fibres are stimulated together, gate will be closed& pain is not felt
  • 36. Gate control theory• This theory provided basis for various methods of pain relief – Massaging a painful area – Applying irritable substances to a painful area (counter-irritation) – Transcutaneous Electrical Nerve Stimulation (TENS) – Acupuncture ?
  • 37. Gate control theory• But the anatomcal basis for all the connections of Wall’s original diagram is lacking ? ?
  • 38. WDR (wide dynamic range cells) • It is known that some of the second order neurons of the pain pathway behave as wide dynamic range neurons • they can be stimulated by pain stimuli but inhibited by touch stimuli
  • 39. WDR (wide dynamic range cells) pain & mech mech C fibre A fibre excitatoryWDR cell inhibitory
  • 40. WDR cells• have been found in – Spinal cord – Trigeminal nucleus – Brain stem – Thalamus – Cortex
  • 41. Modifications to the gate control theory• this could be modified in the light of enkephalin activity and WDR cells• inhibitory interneuron may be substantia gelatinosa cell• descending control is more important• WDR cells may represent neurons having pain as well as touch input
  • 42. referred pain• sometimes pain arising from viscera are not felt at the site of origin but referred to a distant site. – eg. • cardiac pain referred to the left arm • diaphargmatic pain referred to the shoulder – this paradoxical situation is due to an apparent error in localisation
  • 43. referred pain - theories• convergence theory – somatic & visceral structures converge on the same somatic dermatome – generally impulses through +++ visceral pathway is rare ++ + – centrally brain is programmed second to receive impulses through visceral order + somatic tract only neuron – therefore even if the visceral structure is stimulated brain misinterpret as if impulses are coming from the somatic structure
  • 44. referred pain - theories• facilitatory theory – somatic & visceral structures converge on the same somatic dermatome – stimulation of visceral +++ structure facilitates ++ + transmission through somatic second tract order + visceral neuron
  • 45. • hypoxia / pressure / inflating a BP cuff – first affect large A fibres (touch & pressure sense) – then affect Aδ fibres (temperature sense & pricking pain) – lastly C fibres (burning pain)• local anaesthetics – first relieve burning pain ( C fibres) – then temperature sense & pricking pain (Aδ fibres) – lastly touch& pressure sensation (large A fibres)
  • 46. Pain arising from abdominal viscera• Mediated by C fibres• Mainly due to the sensations of distention, muscular contraction, inflammation, hypoxia but not to cutting, tearing, local irritation, burning• Typically vague, dull, and nauseating• These structures are innervated by autonomic nerve fibers• It is poorly localized and tends to be referred to areas corresponding to the embryonic origin of the affected structure – stomach, duodenum, liver and pancreas referred to upper abdomen – small intestines, proximal colon and appendix referred to periumbilical pain – distal colon and GU tract referred to lower abdominal pain• Peritonitis causes somatic pain• Diffuse localization of true visceral pain is probably due to the low density of visceral sensory innervation and extensive divergence of the visceral input within the central nervous system
  • 47. Capsaicin and vanniloid receptors• Active compound in chilies is capsaicin• Capsaicin chemically is one of the vanilloids• Capsaicin receptor is called TRPV1 – (Transient receptor potential vanilloid type 1)• This receptor is also stimulated by – heat greater than 43°C – low pH• This receptor is sensitised by prostaglandins and bradykinins• Upon prolonged exposure to capsaicin TRPV1 activity decreases – this phenomenon is called desensitization – Extracellular calcium ions are required for this phenomenon – This causes the paradoxical analgesic effect of capsaicin
  • 48. Cannabinoid receptor• Cannabis (marijuvana or ganja) causes pain relief• Cannabis act on cannabinoid receptors found in pain pathway• There are endocannabinoids as well• Cannabinoid receptor-related processes are involved in cognition, memory, anxiety, control of appetite, emesis, motor behavior, sensory, autonomic and neuroendocrine responses, immune responses and inflammatory effects
  • 49. Neurotransmitters in the CNS• Excitatory – Substance P – Glutamate (NMDA receptor) – Neurokinin A and B – calcitonin gene-related peptide – vasoactive intestinal polypeptide – Somatostatin – bombesin
  • 50. Neurotransmitters in the CNS• Inhibitory – GABA – Noradrenalin – Serotonin – Enkephalins
  • 51. Pain memory• Memory of pain can be more damaging than its initial experience• Central sensitization – Increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input• Peripheral sensitization – Increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation of their receptive fields• Clinical interventions to blunt both the experience and persistence of pain or to lessen its memory are now applied• Preemptive analgesia – Pre-emptive analgesia is a treatment that is initiated before the surgical procedure in order to reduce sensitization – Many studies have demonstrated that analgesic intervention before a noxious stimulus or injury is more effective at averting central sensitization than the same analgesic intervention given after the stimulus