1. Scientific Basic of Pain RM Clemmons, DVM, PhD, CVA. CVFT University of Florida

2. PAIN Unpleasant sensory and emotional experience associated with actual or potential tissue damage Functions: Stop Signal Warning of a threat Basis of learning Forces a person to rest

3. Terminology Noxious – harmful, injurious Noxious stimuli – stimuli that activate nociceptors (pressure, cold/heat extremes, chemicals) Nociceptor – nerve receptors that transmits pain impulses Pain Threshold – level of noxious stimulus required to alert an individual of a potential threat to tissue Pain Tolerance – amount of pain a person is willing or able to tolerate Hyperesthesia – abnormal acuteness of sensitivity to touch, pain, or other sensory stimuli Paresthesia – abnormal sensation, such as burning, pricking, tingling Analgesic – a neurologic or pharmacologic state in which painful stimuli are no longer painful

4. Overview of Neural Integration Figure 15.1

5. Neural pathways Afferent pathways Sensory information coming from the sensory receptors through peripheral nerves to the spinal cord and on to the brain Efferent pathways Motor commands coming from the brain and spinal cord, through peripheral nerves to effecter organs

6. 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

7. Specialized cell or cell process that monitors specific conditions Arriving information is a sensation Awareness of a sensation is a perception Sensory receptor

8. General senses Pain Temperature Physical distortion Chemical detection Receptors for general senses scattered throughout the body Special senses Located in specific sense organs Structurally complex Senses

9. Each receptor cell monitors a specific receptive field Transduction A large enough stimulus changes the receptor potential, reaching generator potential Sensory receptors

10. Figure 15.2

11. Provide information on pain as related to extremes of temperature Provide information on pain as related to extremes of mechanical damage Provide information on pain as related to extremes of dissolved chemicals Myelinated type A fibers carry fast pain Slower type C fibers carry slow pain Three types of nociceptor

12. Found in the dermis Mechaniceptors Sensitive to distortion of their membrane Tactile receptors (six types) Baroreceptors Proprioceptors (three groups) Thermoceptors and mechaniceptors

13. Skin Tactile Receptors Figure 15.3a-f

14. 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, Golgi Tendon Organs Nociceptors – painful stimuli mechanosensitive chemosensitive

15. 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: Respond to phasic activity - produce an impulse when the stimulus is  or , but not during sustained stimulus; adapt to a constant stimulus (Meissner’s corpuscles & Pacinian corpuscles) Respond to tonic receptors produce impulses as long as the stimulus is present. (muscle spindles, free n. endings, Krause’s end bulbs)

16. Nerve Endings 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

17. 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 Hyperalgesia Primary Hyperalgesia – due to injury Secondary Hyperalgesia – due to spreading of chemical mediators

18. 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)

19. Second Order Neurons Receive impulses from the FON in the dorsal horn Lamina II, Substantia Gelatinosa (SG) - determines the input sent to T cells from peripheral nerve T Cells (transmission cells): transmission cell that connects sensory n. to CNS; neurons that organize stimulus input & transmit stimulus to the brain 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

20. 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

21. Descending Neurons Descending Pain Modulation (Descending Pain Control Mechanism) Transmit impulses from the brain (corticospinal tract in the cortex) to the spinal cord (lamina) Periaquaductal Gray Area (PGA) – release enkephalins Nucleus Raphe Magnus (NRM) – release serotonin The release of these neurotransmitters inhibit ascending neurons Stimulation of the PGA in the midbrain & NRM in the pons & medulla causes analgesia. Endogenous opioid peptides - endorphins & enkephalins

22. 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

23. Three major pathways carry sensory information Posterior (Dorsal) column pathway Anterolateral pathway Spinocerebellar pathway Somatic Sensory Pathways

24. Figure 15.6 Ascending Tracts in the Spinal Cord

25. Carries fine touch, pressure and proprioceptive sensations Axons ascend within the fasciculus gracilis and fasciculus cuneatus Relay information to the thalamus via the medial lemniscus Posterior column pathway

26. Figure 15.8a, b Dorsal Columns & Spinothalamic Tracts

27. Carries poorly localized sensations of touch, pressure, pain, and temperature Axons decussate in the spinal cord and ascend within the anterior and lateral spinothalamic tracts Headed toward the ventral nuclei of the thalamus Spinothalamic pathway

28. Role of Thalamus Second order neurons transmit pain and temperature signals to thalamus contralateral to stimulated receptor VPM processes pain and temperature signals from trigeminal (CNV) analog of spinothalamic system for head and neck VPL processes pain and temperature signals from peripheral regions of the body such as viscera, trunk and limbs Medial (intralaminar) thalamic nuclei process pain and temperature signals from reticular formation (spinoreticular fibers) such as raphe nuclei and locus coruleus Central (thalamic) pain signals cannot be localized (e.g., metastatic cancer) and central (thalamic) pain syndrome is relieved by producing electrical lesions in a thalamotomy procedure

29. Role of Cerebral Cortex Pain and temperature signals transmitted from VPL and VPM (specific thalamic nuclei) to somatosensory cortices SI and SII for localization Pain and temperature signals transmitted from medial intralaminar (nonspecific) nuclei to all regions of cerebral cortex for “alerting” response, which induce wakefulness and inhibit sleep Pain and temperature signals also transmitted from intralaminar nonspecific nuclei to limbic system, hypothalamus and associated structures for emotional, endocrine, stress and autonomic responses which produce fear, suffering, cardiovascular, respiratory, gastrointestinal, urogenital and stress-related hormonal responses

30. 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 @ 1 st & later may be localized (i.e. appendicitis) Psychogenic Pain individual feels pain but cause is emotional rather than physical

31. Types of Pain: Classification by Duration Acute pain An unpleasant experience with emotional, cognitive, and sensory features, resulting from tissue trauma Usually associated with significant, observable tissue pathology Resolves with healing of causative injury Protective biological function to protect against further injury; protective reflexes include withdrawal, muscle spasm, and autonomic reactions Acute vs chronic 1 Chronic pain Pain lasting beyond expected recovery period and identifiable pathology insufficient to explain the pain state Disrupts sleep and normal activities of living Does not serve a protective, adaptive function

32. Types of Pain: Classification by Etiology Nociceptive pain Results from normal function of the nervous system Caused when a noxious stimulus (eg, trauma, inflammation, infection) activates A-delta and C nociceptors —Visceral pain: originates in internal organs —Somatic pain: originates in skin, muscle, skeletal structures Nociceptive vs neuropathic 1 Neuropathic pain Abnormal nociceptive signaling caused by an impairment of the nervous system Serves no functional or adaptive purpose Causes and examples — Metabolic: diabetic neuropathy — Infectious: herpes zoster — Trauma: nerve entrapment

33. The Neurophysiology of Pain Nociception: process by which information about tissue damage reaches the central nervous system Transduction Transmission Perception Modulation

34. Pain Transduction Nociceptor = pain receptor: specialized receptor for detecting tissue injury/damage Two classes of nociceptive afferent fibers A-delta axonC axon TypeA-deltaC Caliber Small diameter, thinly myelinated Small diameter, unmyelinated Stimuli Thermal & high-threshold mechanical Polymodal: high-intensity mechanical, chemical, heat, cold Conduction velocity (meters/sec) 5-300.5-2 Effect of activation Short, sharp, prickling pain More prolonged sensation of dull pain

35. Pain Transduction Nociceptors do not spontaneously depolarize: they send impulses (action potentials) only when stimulated No specialized pain “receptors” The receptor region of the nociceptor is the free terminal of the axon Ion channels in nerve terminal open in response to noxious stimuli, initiating an action potential, the “pain signal” Peripheral sensitization: local tissue injury with release of inflammatory mediators can enhance nociceptor response

36. Small Diameter Afferent Fibers Cutaneous mechanoreceptors Respond to nondiscriminative tactile stimuli Pinch, rub, stretch, squeeze A-delta and C fiber, high-threshold Cutaneous thermoreceptors Respond to transient change in temperature Innocuous ward and cool stimuli

37. Small Diameter Afferent Fibers Cutaneous nociceptors – cutaneous pain A-delta mechanoreceptors Mechanical tissue damage C-polymodal nociceptors Mechanical tissue damage, noxious thermal stimuli, endogenous algesic chemicals C-fiber mechanonociceptors A-delta heat thermonociceptors A-delta, C-fiber cold thermonociceptors C-fiber chemonociceptors – algesic chemicals

39. Pain Transmission Nociceptors  (primary sensory afferents) have cell body in dorsal root ganglia; synapse to second-order neurons in dorsal horn of spinal cord Pain impulses can trigger a withdrawal reflex via connections to motor neurons in the spinal cord Impulses ascend to brain via various ascending tracts

40. CNS Neurotransmitters of A-delta and C-fibers Substance P (Neuropeptide) Calcitonin Gene Related Peptide (CGRP) Excitatory amino acids – e.g., glutamate Release in ischemia/hypoxia - neurotoxicity

41. Pain Perception Perception of and reaction to pain are influenced by social and environmental cues, as well as by cultural norms and personal experience Both cortical and limbic systems are involved in conscious awareness (perception) of pain Recognition of location, intensity, and quality of pain is mediated by processing of signals from the spinothalamic tract > thalamus > somatosensory cortex Pain information processing in the brainstem, midbrain, and limbic system appear to mediate affective, motivational, and behavioral responses to painful stimuli

42. Pain Modulation Gate  control theory advanced by Melzack and Wall in 1965 focused on descending pathways from the brain to the spinal cord that inhibit pain signaling Current view: signals originating in the brain can both inhibit and facilitate pain signal transmission Neurotransmitters involved in these pathways include Endogenous opiates (enkephalins, dynorphins, beta- endorphins) Serotonin Norepinephrine

43. Pain Control Theories Gate Control Theory Central Biasing Theory Endogenous Opiates Theory

44. Gate Control Theory Melzack & Wall, 1965 Substantia Gelatinosa (SG) in dorsal horn of spinal cord acts as a ‘gate’ – only allows one type of impulses to connect with the SON Transmission Cell (T-cell) – distal end of the SON If A-beta neurons are stimulated – SG is activated which closes the gate to A-delta & C neurons If A-delta & C neurons are stimulated – SG is blocked which closes the gate to A-beta neurons

45. 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 1 st inhibit pain impulses (acupuncture/pressure, cold, heat, chem. skin irritation). Brain Pain Heat, Cold, Mechanical Gate ( T cells/ SG)

46. Central Biasing Theory Descending neurons are activated by: stimulation of A-delta & C neurons, cognitive processes, anxiety, depression, previous experiences, expectations Cause release of enkephalins (PAG) and serotonin (NRM) Enkephalin interneuron in area of the SG blocks A-delta & C neurons

47. Endogenous Opiates Theory Least understood of all the theories Stimulation of A-delta & C fibers causes release of B- endorphins from the PAG & NRM Or ACTH/B-lipotropin is released from the anterior pituitary in response to pain – broken down into B- endorphins and corticosteroids Mechanism of action – similar to enkephalins to block ascending nerve impulses Examples: TENS (low freq. & long pulse duration)

48. Goals in Managing Pain Reduce pain! Control acute pain! Protect the patient from further injury while encouraging progressive exercise

49. Other ways to control pain Encourage central biasing – motivation, relaxation, positive thinking Minimize tissue damage Maintain communication If possible, allow exercise Medications

51. Romance 10 month old Golden Retriever 2 weeks history of lip twitches & abnormal behavior Mild CP deficit in R rear leg S

52. Romance Localization of LesionLocalization of Lesion D A M N N I I I T T V O Cerebral (Forebrain) Genetic Encephalitis GME Brain Tumor Liver Disease Epilepsy

53. Romance P Problem List Differential Dx ? Diagnostic Approach ? Treatment ? 1.Facial Twiches 2.Ataxia 3.Behavioral Change 1.Inf/Inflam 2.Neoplasia 3.Inborn Error 4.Liver 5.Epilepsy

54. Romance- -Diagnostic Approach MDB CBC Chemistry Profile UA Chest & Abdominal Radiographs Abdominal Ultrasound Bile Acids Cholinesterase Ammonia level Neurologic Tests EEG CSF Analysis Cisternal Titers MRI Client Education P

55. Romance- -CBC O

56. Romance- -Chemistry O

57. Romance- -UA O

58. Romance- -MRI LL O

59. Romance- -CSF Analysis SPECIMEN: CSF – AO Color/Transparency: colorless/clear Protein mg/dL 16 RBC/μL 46 WBC/μL 14 A 32 cell differential count yielded the following: 13 Neutrophils 5 Lymphocytes 14 Mononuclear phagocytes Two cytospin preparations are stained and microscopically examined. The slides are of adequate staining and preservation of cellular detail with scant hemodilution present against a colorless background that contains occasional squamous epithelial contaminants. Approximately equal numbers of mature, nondegenerate neutrophils and variably reactive mononuclear phagocytes are the predominant cell types. Small, well-differentiated lymphocytes are infrequently identified. No infectious agents or neoplastic cells are identified. Interpretation: Mild, mixed pleocytosis. O

60. Romance- -Titers (Serum) 3DX - Negative for Dirofilaria immitis antigen, Borrelia burgdorferi and Ehrlichia canis antibody. RMS - Negative for Rickettsia rickettsii IgG AB by IFA: Titer <64 BLM - Negative for Blastomyces by AGID. DIS- CDVIgG AB: 50 IgM AB: Negative CRC - Negative for Cryptococcus antigen by latex agglutination test TO1 – ToxoplasmaIgG AB: Negative IgM AB: Negative NEO - Negative for Neospora caninurn IgG AB by IFA: Titer <50 O

61. Romance- -Final Diagnosis Seizures Secondary to GME A

62. Romance- -Client Education The prognosis is guarded to poor May continue to progress over 3-6 months Treat phenobarbital anti-inflammatory and anti-cancer drugs Consider CAVM & TCVM approaches to augment or instead of Western therapy P

63. Romance- -TCVM exam Tongue Red/purple Pulse Superficial Slippery Fast Sensitivity BL 15 Nao Shu TCVM Diagnosis Damp Heat with Internal Wind

64. Romance- -TCVM Therapy AP Cranial points GV 20 GV 21 An Shen Meng Men (staple) GB 20 Cancer points LI 4 PC 6 GV 14 SP 9 ST 40 LIV 3 Herbal Mind Damp Heat Formula Jing Tang Di Tan Tang Jing Tang

65. Mansion of Mind Damp-Heat LoniceraJin Yin HuaClear heat, Expel wind20 gm ForsynthiaLian QiaoClear heat, Detoxify20 gm IsatidisBan Lan GenClear heat, Cool blood20 gm AstragalusHuang Qi Move Qi (stimulate immune system)20 gm Akebia Mu Tong Drain Damp-Heat 10 gm PlatycodonJie GengTransporter15 gm LicoriceGan CaoHarmonizer10 gm Encephalitis, SRME, GME

66. Cody History of brainstem tumor leading to secondary hydrocephalus ~2.5cm mass Probable meningioma TCVM Dx Blood Stagnation

67. Cody (13 months) Western Rx Phenobarbital Prednisone TCVM Stasis in Mansion of Mind formula Di Tan Tang Max formula

68. History After electro-acupuncture (EA) analgesia was found effectively to perform a surgery in China in the early 1970's, EA has been widely used in TCM practice. Electro-acupuncture techniques

69. Advantage: More effective Less treatments Less acupoints Save labor to manipulate the needles (Classically, the needles should be manipulated every 2 to 3 minutes). Objective control of frequency and amplitude Amplitude (intensity of stimulation): a tolerance level Frequency: Low level: pain ----> beta endorphin mediated High level: internal medicine  > serotonin mediated

70. Acupuncture Points: 6 to 10 points Frequency: 20 HzOr 80 to 120 Hz Electrical intensity: gradually goes to the points the patient can tolerate. Methods: Pain management Bi syndromes (arthritis) Soft tissue injuries Disc problems Colic/abdominal pain Peripheral nerve paralysis Facial Radial Others Gastrointestinal conditions: vomiting, diarrhea, constipation, indigestion Muscle atrophy Indications:

71. Contraindications: 1) Weak/deficient patients 2) Heart problems 3) Seizure/epilepsy 4) Tumor

72. 1.Dial the AMPLITUDE and FREQUENCY to zero; 2.Plug the wire leads into sockets 1 to 7 and fasten the clips to the handles of needles; 3.Set the desirable frequencies and wave forms Frequency: Low frequency (F1 = 20-30 Hz) Indication: pain conditions---Endorphin release Moderate frequency (F1=80 to 120 Hz) Indications: internal medical conditions (diarrhea etc)- -Enkephalin High frequency (F1=200 Hz) Indication: pain conditions- -Serotonin release How to Use EA

73. Wave Form: depends on how F1 and F2 is set up Continuing Wave: F1=20-200; F2=0 Indications: pain conditions Intermittent wave:F1=0; F2=40 Indications: muscular atrophy Dense and Disperse (DD) wave: F1=80; F2 =120 Indications: nerve paralysis and internal medical conditions How to Use EA

74. 4.Turn on the power 3 5.Gradually increase AMPLITUDE buttons until the patient can tolerate. a)Can increase amplitude a little bit every 5 minutes. 6.The duration of a treatment session: 10 to 30 minutes. 4.Turn off power to terminate the acupuncture treatment. How to Use EA

75. EA: how to pair the points 1) Bilateral connection a. Pair BL-54 on left side to right BL54 for hip dysplasia; b. Hua-tuo-jia-ji on the left to right side for disk diseases c. BL-21 on the left to right BL-21 for vomiting d. KID-1 on the left to right KID-1 for rear weakness e. Left Ding-chuan + right Ding-chuan for cough 2) Same Channel connection. a. GV-14 + Bai-hui for disk disease b. LI-10 + LI-15 on the same side for shoulder pain c. Tip of tail + GV-20 for vestibular dx, disk disease 3) Local connection a. TH-14 + LI-15 on the same side for shoulder pain b. GB-34 + ST-35 on the same side for stifle pain 4) Same energetic connection ST-36 + GB-34 on the same side for vomiting, rear weakness ST-36 + BL-20 on the same side for SP Qi deficiency The general rules: The same lead to pair 2 points

76. 5) From the top to bottoms for paralysis a. BL-54 + KID-1 for rear limb paralysis b. PC-8 + GV-14 for front limb paralysis c. GB-21 + HT-3 for front limb paralysis 6) Cover large areas a. BL-20 on the left + right BL28 for T-L-S IVDD 7) Normal area to sick area a. BL-21 to KID-1 for no deep pain caudal to BL-22 b. ST-5 left to right for right facial paralysis EA: how to pair the points

77. But, we must pay attention to the following: 1) The wire (lead) should NOT be connected around the abdominal areas for pregnant moms. 2) The wire (lead) should NOT be connected through the chest if the patient has a pacemaker. 3) The wire (lead) should NOT be connected through the tumor mass. 4) Caution for seizure dogs when using EA EA: how to pair the points

79. GOD cures, Doctors send the bill! -Mark Twain