WSVMA Annual Conference

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1 WSVMA Annual Conference Scientific Basis of Acupuncture Analgesia Spokane Convention Center Spokane, Washington October 1-3, 2010 Stephen Greene, DVM, MS, DACVA Washington State University College of Veterinary Medicine

2 Stephen Greene, DVM, MS, Diplomate ACVA Washington State University Pullman, WA Biography: Dr. Greene received his DVM from the University of Missouri-Columbia in He worked two years as a post-doctoral fellow studying environmental toxins at the Lovelace Biomedical & Environmental Research Institute in Albuquerque. He then completed his MS degree and residency training in Veterinary Anesthesiology from the College of Veterinary Medicine, University of Illinois, Urbana, in After an initial position as Assistant Professor of Anesthesia at Texas A&M University, Dr. Greene arrived to teach anesthesia at WSU-CVM in He attended the IVAS course for acupuncture in Calgary in Dr. Greene has since incorporated introductions to acupuncture and TCM into the veterinary anesthesia and pain management courses at WSU. Contact sag@vetmed.wsu.edu

3 Scientific Basis for Acupuncture Analgesia Stephen Greene, DVM, MS, DACVA Professor of Veterinary Anesthesia Washington State University Treatment of Chronic Pain Chronic pain frequently involves different mechanisms of signal transmission or transduction along the pain pathway compared to acute pain. The successful treatment of chronic pain syndromes may involve therapies that act through these other routes. The Analgesic Ladder promoted by the World Health Organization illustrates the graded steps for treating chronic pain. The use of analgesic adjuvants includes pharmacologic agents and non-pharmacologic methods for controlling pain. Acupuncture-induced analgesia is generally very well tolerated by animals and offers a treatment modality for control of chronic pain that avoids excessive CNS or cardiovascular depressant side effects. Using PET scans in humans, common areas of the brain have been identified that undergo activation during both pain sensation and nonpainful acupuncture stimulation: left anterior cingulate cortex, bilateral insulae, and cerebellum. Acupoint Stimulation 1.Dry needling (unidirectional needle rotation) 2.Transcutaneous electrical 3.Electroacupuncture 4.Laser light 5.Heat (moxa) 6.Massage 1

Ultrasound scanning microscopy: A) No rotation; B) Rotation Responses to Acupoint Stimulation 1.

point (Governing Vessel 26) Bai hui- sedation point (Governing Vessel 20) Electroacupuncture-Induced Analgesia (EAA)

by which beta-endorphin by-passes the bloodbrain barrier (activates descending inhibitory system) beta-endorphin released

4 Ultrasound scanning microscopy: A) No rotation; B) Rotation Responses to Acupoint Stimulation 1. Humoral release of transmitter substances Beta-endorphin Histamine Substance P Catecholamines Sympathetic stimulation point (Governing Vessel 26) Bai hui- sedation point (Governing Vessel 20) Electroacupuncture-Induced Analgesia (EAA) Release of endogenous opioids Pituitary release of beta-endorphin into systemic circulation Hypothalamic-midbrain axons by which beta-endorphin by-passes the bloodbrain barrier (activates descending inhibitory system) beta-endorphin released into CSF enkephalin released by periaqueductal grey region activates the raphe nucleus magna descending inhibitory system (via release of 5-HT & NOREPI) 2

5 Low Frequency stimuli (2 Hz) Beta-endorphin Enkephalin Endomorphin Mu and delta opioid agonists High Frequency stimuli (100 Hz) Dynorphin (kappa opioid agonist) Beta-endorphin release & descending inhibition of pain Thalamus Inhibitory Thalamus Endorphin Cortex Endorphin Cortex Endorphin Endorphin Systemic Circulation Skin Spinal Cord Muscle Midbrain Pituitary Skin Spinal Cord Muscle Midbrain Pituitary Characteristics of electroacupuncture-induced analgesia EAA Decreased by: Serotonin blockers Atropine Naloxone Dopamine agonists Al h i t EAA Increased by: Acetylcholine 5HT Dopamine antagonists Alpha antagonists 2. Anti-inflammatory effect Either low or high frequency EA 3

6 Antagonized by parasympathetic blockers Decreased edema Decreased B- and T-cell responses Increased activity of natural splenic killer cells Mediator Function Histamine, leukotrienes, prostaglandin E1 & E2 Altered vasopermeability, egress of immune cells, antibody, and compliment Substance P Kallikrein, bradykinin Plasmin, heparin, prostacyclin, lysosomal enzymes Platelet activating factor, thromboxanes, serotonin (5HT), thrombin Excitation of A-delta and C fibers (nociception), vasodilation Release of histaminase and lysosomal antibodies, phagocytosis, antibody production, lymphokine production, chemotactic stimulation Compliment activation, fibrin lysis, thrombin inhibition, platelet disaggregation, clearance of damaged tissue components Platelet aggregation, degranulation and attraction, vasoconstriction, fibrinogen conversion (clot formation) Histaminase, epinephrine, corticosteroids Histamine breakdown, increased camp, inhibition of arachidonic acid formation 3. Direct neuronal stimulation a. Acupuncture needle stimulation of specific neurons can inhibit CNS sensitization resulting from painful stimuli (NMDA-receptor antagonism) 1) Inhibition of hyperalgesia 2) Inhibition of neuropathic pain b. Autonomic nervous system stimulation 1) Sympathetic stimulation 2) Cholinergic stimulation 4

7 General Acupoints for Joint Pain & Arthritis BL 60: aspirin point, relaxes muscles LV 3: relieves stagnation BL 40: relieves inflammation in pelvic limb BL 23: Kidney association pt., warming, strengthens bone GB 34: strengthens tendons SP 9: clears dampness ST 36: strengthens chi, immune system & bone Cutaneovisceral reflex McBurney s point: recognized in Western medicine as a cutaneous site in the lower abdomen that is reactive (sensitive) in human patients with appendicitis. Corresponds to Stomach 25, the Alarm Point for the Large Intestine in TCM. 4. Semi-conducting collagen network of hydrogen ion transfer a. Water molecules are bound to collagen fibers throughout connective tissue. b. This network has high conductivity (up to 100 X the speed of neurons). c. These fast, weak electrical currents may constitute the meridians for flow of Qi. d. Infrared thermographic imaging supports the rapid appearance of heatgenerated proton transfer (moxibustion) along meridians. 5

8 5. Cholecystokinin antagonism Cholecystokinin octapeptide (CCK-8) has been shown to antagonize betaendorphin, thereby playing a role in development of tolerance to opioids and acupuncture analgesia in some patients. Non-responders to acupuncture analgesia can be converted to responders following injection of drugs that antagonize CCK. Summary 1. Humoral mediators of analgesia (beta endorphin) 2. Anti-inflammatory effects 3. Direct neuronal stimulation 4. Proton transfer (collagen semi-conduction) 5. Cholecystokinin antagonists Case Example: EAA for chronic hip pain/osteoarthritis Acupoint selection: BL 23, 40; GB 29, 30, 34; ST 36 Electrodes: Paired to ipsilateral points Positive electrode on lower numbered acupoint on meridian Stimulation: Low frequency (< 5 Hz) or alternating (dense/disperse) pattern Short duration: minutes Supervised References General Reviews 1. Clemmons RM: Functional neuroanatomical physiology of acupuncture in Xie s Veterinary Acupuncture, p , Blackwell Publishing, Lin J-G and Chen W-L: Acupuncture analgesia: A review of its mechanisms of actions. Am J Chinese Med 36: , Clinical Acupuncture - Scientific Basis, Hammerschlag, R and Stux G, eds. Springer,

9 4. Ho MW, Knight DP: The acupuncture system and the liquid crystalline collagen fibers of the connective tissues. Am J Chin Med. 26(3-4):251-63, Mohammed OF, Pines D, Dreyer J, Pines E, Nibbering ETJ: Sequential proton transfer through water bridges in acid-base reactions. Science 310:83-86, Human Studies 1. Greif, R et al.: Transcutaneous electrical stimulation of an auricular acupuncture point decreases anesthetic requirement. Anesthesiology 96: , Leibing E. et al.: Acupuncture treatment of chronic low-back pain a randomized, blinded, placebo-controlled trial with 9-month follow-up. Pain 96: , Canine Studies 1. Kapatkin AS, et al. Effects of electrostimulated acupuncture on ground reaction forces and pain scores in dogs with chronic elbow joint arthritis. JAVMA 228:1350-4, Jaeger GT, et al. Double-blind, placebo-controlled trial of the pain-relieving effects of the implantation of gold beads into dogs with hip dysplasia. Vet Rec 158:722-6, Culp LB, et al. Comparisons of the effects of acupuncture, electroacupuncture, and transcutaneous cranial electrical stimulation on the minimum alveolar concentration of isoflurane in dogs. AJVR 66: , Iwa M, et al. Electroacupuncture reduces rectal distension-induced blood pressure changes in conscious dogs. Dig Dis Sci 50: , Pomeranz 17 Lines of Evidence from Clinical Acupuncture Scientific Basis 1. Many different opiate antagonists block acupuncture analgesia (AA) 2. Naloxone blocks AA in a stereospecific manner 3. Injection of naloxone or anti-endorphin antibodies blocks only if injected into specific analgesic sites 4. Mice deficient in opiate receptors show poor AA 5. Rats deficient in endorphin show poor AA 6. Endorphin levels in blood increase during AA 7. AA is enhanced by protecting endorphins from degradation 8. AA is transmissible by transferring CSF from subject to a second animal and is blocked by naloxone 9. Reduction of pituitary endorphins suppresses AA 10. EA causes an increase in mrna for proenkephalin that lasted 24-48h 11. There is cross-tolerance between AA and morphine analgesia 12. AA is more effective against emotional aspects of pain 13. Lesions of the arcuate nucleus abolish AA 14. Lesions of the periaqueductal gray matter abolish AA 15. Protein cfos (a neuronal activity marker) expressed more in endorphin areas of the brain during AA 16. High frequency EA increases levels of monoamines and dynorphin 17. EA in rats increases the precursors of all three classes of endorphins mrna 7

Receptors and Neurotransmitters: It Sounds Greek to Me. Agenda. What We Know About Pain 9/7/2012

Receptors and Neurotransmitters: It Sounds Greek to Me Cathy Carlson, PhD, RN Northern Illinois University Agenda We will be going through this lecture on basic pain physiology using analogies, mnemonics,