Pain – Anatomy and Physiology

1. Pain – Anatomy and Physiology

2. Definition An unpleasant sensory and emotional experience... ...caused by actual or potential tissue injury, ...or described in terms of such injury. International Association for the Study of Pain

3. Sources of Pain Nociceptive: pain that is usually transmitted after normal processing of noxious stimuli Neuropathic: results from injury or abnormal functioning of peripheral nerves or CNS Psychogenic: unknown physical cause

4. Classification of Pain Nociception • Proportionate to the stimulation of the nociceptor • When acute • Physiologic pain • Serves a protective function • Normal pain • Pathologic when chronic

5. Describe the different types of pain sensation • bright, • sharp, • stabbing types of pain • dull, • throbbing, • aching types.

6. Where Does Pain Come From? • Cutaneous Pain – sharp, bright, burning; can have a fast or slow onset • Deep Somatic Pain – stems from tendons, muscles, joints, periosteum, & b. vessels • Visceral Pain – originates from internal organs; diffused @ 1st & later may be localized (i.e. appendicitis) • Psychogenic Pain – individual feels pain but cause is emotional rather than physical

7. Neuropathic Pain • Sustained by aberrant processes in PNS or CNS • Disproportionate to the stimulation of nociceptor • Serves no protective function • Pathologic pain

8. PHYSIOLOGY OF PAIN SOURCES Chemical/Thermal Injury, Inflammation Heat, Cold PAIN RECEPTORS (Nociceptors) DISCHARGE IMPULSES Electrical Activity to spinal cord and onto the Brain BRAIN = Electrical activity becomes the experience of PAIN

9. Sensory Receptors • Mechanoreceptors – touch, light or deep pressure • Meissner’s corpuscles (light touch), Pacinian corpuscles (deep pressure), Merkel’s corpuscles (deep pressure) • Thermoreceptors - heat, cold • Krause’s end bulbs ( temp & touch), Ruffini corpuscles (in the skin) – touch, tension, heat; (in joint capsules & ligaments – change of position) • Proprioceptors – change in length or tension • Muscle Spindles • Nociceptors – painful stimuli • mechanosensitive • chemosensitive

10. Nerve Endings • “A nerve ending is the termination of a nerve fiber in a peripheral structure.” • Nerve endings may be sensory (receptor) or motor (effector). • Nerve endings may be: • Respond to phasic activity - produce an impulse when the stimulus is  or ,) • Superficial – Merkel’s corpuscles/disks, Meissner’s corpuscles • Deep – Pacinian corpuscles,

11. Merkel’s corpuscles/disks - Sensitive to touch & vibration Slow adapting Superficial location Most sensitive Meissner’s corpuscles – Sensitive to light touch & vibrations Rapid adapting Superficial location Pacinian corpuscles - Sensitive to deep pressure & vibrations Rapid adapting Deep subcutaneous tissue location Krause’s end bulbs – Thermoreceptor Ruffini corpuscles/endings Thermoreceptor Sensitive to touch & tension Slow adapting Free nerve endings - Afferent Detects pain, touch, temperature, mechanical stimuli Nerve Endings

12. The skin receptors (transducers) a) Merkel b) Meissner c) Ruffini d) Pacinian

13. Nociceptors • Sensitive to repeated or prolonged stimulation • Mechanosensitive – excited by stress & tissue damage • Chemosensitive – excited by the release of chemical mediators • Bradykinin, Histamine, Prostaglandins, Arachadonic Acid • Primary Hyperalgesia – due to injury • Secondary Hyperalgesia – due to spreading of chemical mediators

15. Nociception Transduction Conduction Transmission Modulation Noxious stimulus “Ouch” Pain primary sensory neuron central neuron

16. Nociception – Transduction Nociceptor Activators Cold Heat H+ Bradykinin Mechanical VR1 ASIC TRPV3 B1/B2 CRM1 DRASIC/mDEG generator potential action potentials COX-2 Insensitive

19. Injury response

22. Pain nerve fibers – fast pain and slow pain • From the pain receptors, the pain stimulus is transmitted through peripheral nerves to the spinal cord and from there to the brain. This happens through two different types of nerves fibers: • A-delta "fast pain” and • C-fibers “slow pain” nerve fibers.

23. What is “fast pain” and “slow pain”? • A pain stimulus, e.g. if you cut yourself, consists of two sensations. • first “fast pain” sensation-is experienced as sharp, bright and localized pain followed by • “slow pain”, more a dull, burning and diffused. • So,pain occurs after a short time, and • lasts a few days or weeks, • Chronic pain-if inappropriately processed by the body, it can last several months

24. Fast pain • Relatively thick size nerve fibers allow the pain stimulus to be transferred very fast (at a speed of five to 30 meter/second), hence the name • Due to activity of A delta fibers • This is all to make the body withdraw immediately from the painful and harmful stimulus, in order to avoid further damage.

25. Slow Pain • starts immediately after the fast pain • is transmitted by very thin nerve fibers, called C-nerve fibers (their diameter is between 0.2 to 1 thousandth of a millimeter). • pain impulse can only be transmitted slowly to the brain, at a speed of less than 2 meters per second. • Body response -immobilization (guarding, spasm or rigidity), so that healing can take place.

27. Types of Nerves • Afferent (Ascending) – transmit impulses from the periphery to the brain • First Order neuron • Second Order neuron • Third Order neuron • Efferent (Descending) – transmit impulses from the brain to the periphery

29. First Order Neurons • Stimulated by sensory receptors • End in the dorsal horn of the spinal cord • Types • A-alpha – non-pain impulses • A-beta – non-pain impulses • Large, myelinated • Low threshold mechanoreceptor; respond to light touch & low-intensity mechanical info • A-delta – pain impulses due to mechanical pressure • Large diameter, thinly myelinated • Short duration, sharp, fast, bright, localized sensation (prickling, stinging, burning) • C – pain impulses due to chemicals or mechanical • Small diameter, unmyelinated • Delayed onset, diffuse nagging sensation (aching, throbbing)

30. Second Order Neurons • Receive impulses from the FON in the dorsal horn • Lamina II, Substantia Gelatinosa (SG) - determines the input sent to Transmission cells from peripheral nerve • Travel along the spinothalmic tract • Pass through Reticular Formation • Types • Wide range specific • Receive impulses from A-beta, A-delta, & C • Nociceptive specific • Receive impulses from A-delta & C • Ends in thalamus

31. Third Order Neurons • Begins in thalamus • Ends in specific brain centers (cerebral cortex) • Perceive location, quality, intensity • Allows to feel pain, integrate past experiences & emotions and determine reaction to stimulus

32. Brain mapping

33. Neurotransmitters • Chemical substances that allow nerve impulses to move from one neuron to another • Found in synapses • Substance P - thought to be responsible for the transmission of pain-producing impulses • Acetylcholine – responsible for transmitting motor nerve impulses • Enkephalins – reduces pain perception by bonding to pain receptor sites • Norepinephrine – causes vasoconstriction • 2 types of chemical neurotransmitters that mediate pain • Endorphins - morphine-like neurohormone; thought to  pain threshold by binding to receptor sites • Serotonin - substance that causes local vasodilation &  permeability of capillaries • Both are generated by noxious stimuli, which activate the inhibition of pain transmission • Can be either excitatory or inhibitory

34. Pain Control Theories • Gate Control Theory • Central Biasing Theory • Endogenous Opiates Theory

35. Endogenous Opiates Theory • Least understood of all the theories • Stimulation of A-delta & C fibers causes release of B-endorphins • Mechanism of action – similar to enkephalins to block ascending nerve impulses • Examples: TENS (low freq. & long pulse duration)

36. Descending Neurons • Descending Pain Modulation (Descending Pain Control Mechanism) • Transmit impulses from the brain (corticospinal tract in the cortex) to the spinal cord (lamina) • release enkephalins • release serotonin

37. Natural Opioids-Endorphins • released from their storage areas in the brain when a pain impulse reaches the brain, • bind to receptors in the pain pathway to block transmission and perception of pain.

38. Central Biasing Theory • Descending neurons are manipulated by: stimulation of A-delta & C neurons, cognitive processes, anxiety, depression, previous experiences, expectations • Mediates release of enkephalins and serotonin

39. Gate Control Theory • Gate - located in the dorsal horn of the spinal cord • Smaller, slower n. carry pain impulses • Larger, faster n. fibers carry other sensations • Impulses from faster fibers arriving @ gate 1st inhibit pain impulses (acupuncture/pressure, cold, heat, chem. skin irritation). Brain Pain Gate (T cells/ SG) Heat, Cold, Mechanical

40. Gate Control TheoryMelzack and Wall 1965. • Physiological and psychological interactions • Suggested spinal gates in the dorsal horn at each segment of the spinal cord • Competition at each gate for heat, touch or pain to be transmitted at each point

46. Pain-Inhibitory and Pain-Facilitatory Mechanisms Within the Dorsal Horn 0 C A-DELTA A-BETA _ _ + Neuronal circuitry within the dorsal horn. Primary afferent neuron axons synapse onto spinothalamic neurons and onto inhibitory and excitatory neurons. STTNEURON + + + TO BRAIN

47. Mechanisms of Pathophysiologic Pain: Central Sensitization Processes • Repeated impulse activity in C nociceptive neurons produces sensitization of neurons over time • Causes hyperalgesia, allodynia, and spontaneous pain

48. Origin of Pain Physical cause — cause of pain can be identified Psychogenic — cause of pain cannot be identified Referred — pain is perceived in an area distant from its point of origin

49. What is Referred Pain? • Occurs away from pain site • Examples: McBurney’s point