Physiology of Pain

Physiology of Pain, Characteristic of pain, Basic consideration of nervous system, Pain receptor, Mechanism of pain causation, Theories of pain, Pathways of pain, Pain Receptors

1. PHYSIOLOGY OF PAIN DR. DHARATI PATEL DEPARTMENT OF PEDODONTICS AND PREVENTIVE DENTISTRY Perhaps the capacity of the human brain falls short of the ability to understand its own complexity -Thibodeau

2. Content Introduction Definition Historical aspect Characteristic of pain B asic consideration of nervous system Pain receptor Mechanism of pain causation Theories of pain Pathways of pain References

3. Introduction Pain is an unpleasant sensory action Seriously impairs the lives of millions of people around the world Described in many ways by patient

4. Pain is Subjective Protective and it is modified by developmental, behavioural , personality and cultural factors It is a symptom Associated signs are crying, sweating, increased heart rate, blood pressure, behavioral changes etc.

5. Produced by real or potential injury to the body localized to the area stimulated but the experience involves the whole being. P ain also imply that the same painful experience may evoke widely different degrees of suffering in different persons, and even in the same person under different circumstances. It is expressed in terms of damage done by the injury

6. In 1984, Bonica reported that nearly 1/3rd of the population in industrialized nations suffer to some extent from chronic pain. This results in loss of billions annually in health care services, loss of work, decreased productivity and disability compensation The clinical management of pain is the primary concern of health professionals around the world.

7. Benefits of pain Pain is a protective mechanism for the body, it occurs whenever any tissues are being damaged, and it causes the individual to react to remove the pain stimulus Gives warning signal – creates awareness of injury Prevents further damage – causing reflex withdrawal of the body Forces the person to rest or to minimize the activities thus enabling the rapid healing of injurious part

8. Definition

9. Terminologies

10. Historical aspect Homer  pain was due to arrows shot by the gods Aristotle  a “passion of the soul” that somehow resulted from intensification of other sensory experience Plato  pain and pleasure arose from within the body i.e. pain is an emotional experience more than a localized body disturbance Bible  anguish of the soul Freud  symptoms such as pain could develop as a solution to emotional conflicts

11. 1664 AD - Descartes introduced the concept of pain pathway . Recent years – Specialization of nociceptive pathways have been identified .

12. Incidence of pain According to Cohen – It was found that 21.8% of adult in the United States experience orofacial pain symptoms within 6 months of study. The most common pain was toothache, which was estimated to have occurred in 12.3% of the population

13. Characteristic of pain

14. Threshold and Intensity If the intensity of the stimulus is below the threshold (sub-threshold) pain is not felt. As the intensity increases more and more, pain is felt more and more according to the Weber-Fechner’s law. This law ensures that while our body can perceive pain due to low intensity stimulus, a severe crushing injury will not cause death due to pain sensation, yet as stimulus increases, sense of perception also increases.

15. Adaptation Pain receptors show no adaptation and so the pain continues as long as receptors continue to be stimulated. Localization of pain Pain sensation is somewhat poorly localized. However superficial pain is comparatively better localized than deep pain. Rate of damage damage = intensity of pain If the rate of tissue injury (extent of damage per unit time) is high, intensity of pain is also high.

16. THE BASIC NEURAL ANATOMY

17. The human being is a phenomenal organism with the complexity far beyond the imagination of the best scientific minds Because of its complexity, a master control system, the “Nervous system” …coordinate all the activities. In order to manage the patients pain problem understanding the normal function of the nervous system is necessary

18. Components

19. Neuron It is a structural and functional unit of nervous system Called as “ nerve cell” It is different from other cells in the body in 2 ways: 1. It has processes called as axon & dendrites 2. Does not have centrosome- cannot differentiate

20. C lassification 1.Depending upon the number of poles Unipolar Bipolar Multipolar 2. Depending on function Motor Sensory 3. Depending on length Golgi type I Golgi type II

21. Structure 3 parts Nerve cell body Dendrite Axon

22. Nerve cell body Known as soma or perikaryon Irregular in shape Consists of cytoplasm known as- neuroplasm Covered by cell membrane Cytoplasm contains large nucleus, nissl bodies, neurofibrils , mitochondria and golgi apparatus 2. Dendrite Branched process of neuron It contains nissl granules and neurofibrils Conductive in nature- transmits impulses towards cell body

23. 3. Axon Arise from nerve cell body Extends for a long distance away from cell body

24. Internal structure It has a long central core of cytoplasm – axoplasm Axoplasm covered by tubular membrane-axolemma Axoplasm+ axolemma = axis cylinder of nerve fibre Mylein sheath Axons insulated by myelin sheath Does not form a continuous sheath and is absent at intervals- node of Ranvier Segment of nerve fibre between the nodes – internode Responsible for faster nerve conduction where the impulse jumps from one node to other Acts as an insulator

25. Neurilemma Surrounding the myelin sheath there is thin membrane – neurilemma / sheath of Schwann Contains – Schwann cells The cells have flat & elongated nuclei

26. Classification of nerve- fibers Depending on structure Myelinated Nonmyelinated 2. Depending on distribution Somatic Visceral 3. Depending on origin Cranial Spinal 4. Depending on function Motor sensory

27. 5. Depending on secretion of neurotransmitter Adrenergic Cholinergic

28. Depending on diameter and conduction Type A fibers Alpha fibers : size - 13 to 20 µm, velocity - 70 to 120 m/ s. Beta fibers : size – 6 to 13 µm, velocity – 40 to 70 m/s. Gamma fibers : size – 3 to 8 µm, velocity – 15 to 40 m/s. Delta fibers : size – 1 to 5 µm, velocity – 5 to 15 m/s. Type B fibres Size- 1 to 2 µm, 3-10 m/s. Type C fibers Size – 0.5 to 1 µm, velocity – 0.5 to 2 m/s.

29. Pain receptors

30. Pain receptors

31. GENERAL SENSES SPECIAL SOMATIC VISCERAL SUPERFICIAL DEEP Touch-pressure Thermal Pain Pain Proprioception Pain Baroreception Chemoreception Visual Audition Olfaction Gustation 42

32. Mechanoreceptor Thermoreceptor Nociceptor Electromagnetic receptor Chemoreceptor 43 Basic Sensory Receptors

33. Sensory Receptors : Input to the nervous system is provided by sensory receptors that detect such sensory stimuli such as touch, sound, pain, cold and warmth. All the stimuli capable of evoking pain are noxious because they are associated with actual or potential tissue injury. Sherrington postulated the existence of sensory receptors that sensed noxious agents and called nociceptors . Perception of pain 44 nociception

34. Pain Receptors: Pain Receptors Are Free Nerve Endings. Widespread in the superficial layers of the skin, periosteum , the arterial walls, the joint surfaces, and the falx and tentorium in the cranial vault. Most other deep tissues are only sparsely supplied with pain endings. 45

35. 46 Types of stimuli

36. Fields has described that the subjective experience of pain arises by four distinct processes Transduction Transmission Modulation Perception

37. A pain sensation to reach the cortex from the nosiceptors it requires three neuron sets. NOCICEPTORS BRAIN STEM SPINAL CORD THALAMUS CEREBRAL CORTEX Spinal nerve Cranial nerve B B C C A A A - 1 st order neuron B - 2 nd order C - 3 rd order.

38. Nerve Conduction Resting State Reversal Of Polarity Repolarization

39. Na K Na Na K K K K K Na Na Na Nerve membrane Nodes of ranvier Resting state Reversal of polarity Repolarization MYELINATED NERVE

40. All or none phenomenon: The action potential either happens completely or it doesn’t happen at all. Coding for stimulus intensity: Once generated all action potentials are independent of the stimulus strength, and all action potentials are alike. Strong stimuli cause nerve impulses to be generated more often in a given interval of time than do weak stimuli. Thus stimulus intensity is coded for by the number of impulses generated per sec- i.e. by frequency of impulse transmission.

41. Absolute and Relative refractory period: When a patch of neuron membrane is generating an action potential and it’s Na voltage gates are open, the neuron is incapable of responding to another stimulus no matter how strong it may be  Absolute refractory period. Relative refractory period  is the interval following the absolute refractory period when the Na gates are closed, and the K gates are open, and repolarization is occurring. During this time the axons threshold for impulse generation is substantially elevated. A threshold stimulus is unable to trigger an action potential, but an exceptionally strong stimulus can reopen the Na gates and allow another impulse to be generated.

42. Synapse Or Synaptic Junction: It is a unique junction that mediates the transfer of information from one neuron to the next, or neuron to an effector cell. Types Electrical Chemical

43. Neuronal Sensitization: When the excitatory neurotransmitters are released in the synaptic cleft, the post synaptic neuron is excited and an impulse is started and carried down the axon. If the excitatory neurochemicals remain in the region of the synapse, the neuron can be depolarized quicker with the next release of neurotransmitter. This process is called sensitization . This could be the cause for hyperalgesic state in inflammatory tissues.

44. THEORIES OF PAIN 55

45. It is often assumed that pain is a warning that damage has occurred. But this is not strictly true. Because pain may occur when there is no obvious disease as in primary neuralgias and many diseases does not cause pain, at least in the early stages. So these are various theories being put forward on how nerve impulses give rise to sensation of pain. 56

46. INTENSITY THEORY According to this view, pain is produced when any sensory nerve is stimulated beyond a certain level. In other words pain is supposed to be a non-specific sensation and depends only on high intensity stimulation. But the trigeminal system provides an example against this theory. In case of trigeminal neuralgia the patient can suffer excruciating pain from a stimulus no greater than a gentle touch provided it is applied to a trigger zone. Although, the intensity theory is not accepted, it remains true to say that intensity of stimulation is a factor in causing pain. 57

47. Specificity Theory (Johannes Muller, 1842 ) According to this view, pain is a specific modality equivalent to vision and hearing etc. Just as there are Meissner corpuscles for the sensation of touch, Ruffini end organs supposedly for warmth and Krause end organs supposedly for cold, so also pain is mediated by free nerve endings. Certain psychophysical studies have been regarded as supporting specificity theory. Specialization is known to exist in nervous system and there are well known tracts. But concept of specific nerve ending is no long tenable. The Krause and Ruffini endings are absent from the dermis of about all hairy skin, so it is certain that these structures cannot be receptors for cold and warmth. 58

48. Protopathic and Epicritic theory: Head and Rivers (1908) postulated the existence of two cutaneous sensory nerves extending from the periphery to the CNS. The protopathic system is primitive, yielding diffuse impression of pain, including extremes of temperature and is upgraded. The epicritic system is concerned with tough discrimination and small changes in temperature and is phylogenetically a more recent acquisition . 59

49. Pattern theory ( Goldscheider , 1894): This theory states that pain sensation depends upon spatio – temporal pattern of nerve impulses reaching the brain. According to Woddell (1962) warmth, cold and pain are words used to describe reproducible spatio – temporal pattern, or codes of neural activity evoked from skin by changes in environment. The precise pattern of nerve impulse entering the CNS will be different for different regions and will vary from person to person because of normal anatomical variations. 60

50. Gate Control Theory This theory proposed by Melzack and Wall in 1965 and recently re-evaluated is receiving considerable attention. This theory of pain takes into account the relative in put of neural impulses along large and small fibers, the small nerve fibers reach the dorsal horn of spinal cord and relay impulses to further cells which transmit them to higher levels. The large nerve fibers have collateral branches, which carry impulses to substantia gelatinosa where they stimulate secondary neurons. 61

51. The substantia gelatinosa cells terminate on the smaller nerve fibers just as the latter are about to synapse, thus reducing activity, the result is, ongoing activity is reduced or stopped –gate is closed. The theory also proposes that large diameter fiber input has ability to modulate synaptic transmission of small diameter fibers within the dorsal horn. Large diameter fibers transmit signals that are initiated by pressure, vibration and temperature; small diameter fibers transmit painful sensations. Activation of large fiber system inhibits small fiber synaptic transmission, which closes the gate to central progression of impulse carried by small fibers. 62

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53. Pathways of pain

54. Somatic senses are the nervous mechanisms. Are in contradistinction to the special senses.

55. Classification: The mechanoreceptive senses The thermoreceptive senses The pain sense.

56. Sensory pathways for transmitting somatic signals into CNS Somatic segment Spinal cord Brain The dorsal columm -medial lemniscal system or The anterolateral system. Partially at the level of the thalamus.

57. Dorsal column-medial lemniscal system Composed of large, myelinated nerve fibers At velocities of 30-110m/sec. Has a high degree of spatial orientation. Rapidly and with temporal and spatial fidelity. Touch, vibrating, position from the joints, pressure.

58. Anterolateral pathway Composed of smaller myelinated fibers. At velocities ranging from a few meter per second up to 40m/sec. Less spatial orientation. Does not need transmitted rapidly or with great spatial fidelity. Ability to transmit the broad spectrum of sensory modalities- Pain, warmth, cold, and crude tactile sensations.

59. Anatomy: Originate mainly in: dorsal lamina I, IV, V and VI. Upper terminals mainly two folds: Reticular nuclei of the brain stem The ventrobasal complex and the intralaminar nuclei. Small fraction : Ventrobasal complex of thalamus. Most of : Reticular nuclei Intralaminar nuclei Further proceed.

60. Dual pathways for pain Free nerve endings Use two separate pathways. Fast pain pathway Slow pain pathway

61. Neospinothelmic tract for fast pain: Elicited by either mechanical or thermal pain stimuli By small type AꝽ At velocities between 6 to 30 m/sec. Terminate mainly in lamina I. Can be localized much more exactly. Glutamate is neurotransmitter at the type AꝽ pain nerve fiber.

62. A few fibers: reticular areas of brain stems. Most of : Ventrobasal complex. Can be localized much more exactly. Glutamate is neurotransmitter at the type AꝽ pain nerve fiber.

63. Paleospinothalmic pathway for slow pain Elicited by chemical types of pain stimuli. Sometimes by thermal or mechanical. By type C fibers. Although transmit signals from AꝽ fibers also. At velocities between 0.5 and 2m/sec. Terminate in laminae II and III together called substantia gelatinosa then through short fiber neurons entering to lamina V.

64. Type C secrete glutamate and substance P. Glutamate act instantaneously and last for few milliseconds. Substance P released slowly, building up in concentration over a period of seconds or even minutes. Localization is poor. Localized to major part but not specific point. synaptic , diffuse connectivity.

65. Slow pathway terminates mostly into the brainstem only. 1/10 to ¼ pass : Thalamus. Most of terminate: Reticular nuclei of medulla, pons, mesencephalon Tectal area of mesencephalon deep to the sup. and inf. colliculi. The periaqueductal gray region. This region is important.

66. Surgical interruption Severe and intractable pain: pain nervous pathway can be cut at any one of several points. Lower part of body: cordotomy for few week to a few months. Cordotomy not always successful. Second, cauterize specific pain areas.

67. REFERENCES

68. Bell`s ‘Orofacial pain’, 5 th edition, Jeffrey P. Okeson . 2. Text book of Medical Physiology, 2 nd edition, Chaudhari . 3. Text book of Medical Physiology, 10 th edition, Arther C Gyton . 4. Dental Clinics of North America 1978: 22 (1); 1-61. 5. Text book of ‘Oral medicine’- 10 th edition, Burkett’s. 6. Gray's Anatomy – 38 th Edition, Churchill Eivingstone . 7. Understanding “Medical physiology”- 3 rd edition, R L Bijlani . 8. Core Topics in Pain – Anita Holdcroft , Sian Jagger . 79

69. 80 9. Pain – Wikipedia, the free encyclopedia 10. Rolf- Detlef Treede . Neurophysiological studies of pain pathways in peripheral and central nervous system disorders. J Neurol (2003) 250 : 1152–1161. 11. Ascending Sensory Pathways, Chapter 10. 12. Pain pathway & Medications – Painexplained.ca, The Canadian Pain Society.

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