BEYOND OPIOIDS: ADJUNCTS FOR TREATING PAIN Ronald Januchowski, D.O. 2017 Objectives By the end of the presentation, the learner should be able to: Summarize the risks of opiates when used for non-cancer pain Compare and contrast the mechanisms of pain List some adjunct non-pharmaceutical methods for pain control List adjunct pharmaceutical methods for pain control Devise a treatment plan for a patient using adjunct treatment methods for pain Risks and Epidemiology 1
Risks and Epidemiology 40-80 people die daily from opioidrelated overdoses Economic burden is in the billions In 2014, more than 240 million prescriptions were written for prescription opioids (650,000 prescriptions per DAY) 80% of the global supply of opioids is in the U.S. (99% of hydrocodone prescriptions) Mechanisms of Pain Somatosensory Cortex Prefrontal cortex Thalamus Sharp, localized pain Substance P Glutamate Opioid receptors (-) Endogenous opioids (-) Diffuse, dull pain Glycine (-) GABA (-) Mechanisms of Pain Peripheral Nociceptors stimulated by mechanical, thermal or chemical stimuli Voltage gated sodium channels Voltage gated calcium channels Inflammatory mediators (lymphocytes) Bradykinin Serotonin Prostaglandins Cytokines Hydrogen ion (H+) 2
Mechanisms of Pain Centralized Neuroinflammation Immunologic cell (microglial cells mast cell related) Non-Pharmaceutical Methods for Pain Control Osteopathic Manipulation (lower back pain, chronic daily headaches, neck pain) Cognitive behavioral therapy (anxiety and pain) Eye Movement Desensitization Reprocessing (PTSD and pain) Guided Imagery (chronic pain) Acupuncture (lower back pain) Bio-Acoustical Utilization Device (chronic pain) Nutriceutical Choices Arthritis pain γ-linolenic acid for arthritis pain (from evening primrose and certain other plant oils) avocado-soybean unsaponifiables Devil s claw Chronic daily headaches Feverfew Riboflavin (vitamin B2) Chronic pain Vitamin D 3
Nutriceutical Choices Amino acid precursors Promote neurotransmitter production Modulate pain centrally Glutamine (250 mg-1 gram 3-4x/day) Tyrosine (1000-2000 mg/day) Tryptophan (1000-2000 mg/day) Nutriceutical Choices Anti-inflammatory diets Low glycemic index Adequate protein Adequate Ω-3 fatty acids NSAIDs (oral / Control topical Infliximab and many of the other immunologically based medications Capsaicin cream Lidocaine OPI Topical Opiates 4
Control Centralized mediators Tricyclic antidepressants Amitriptyline (150 mg/nightly) Nortriptyline (100 mg/d) Anti-epileptic medications Gabapentin (3600 mg/d) Pregabalin (300 mg/d) Lamotrigine Control Centralized mediators NMDA receptor antagonists Dextromethorphan (15-30 mg) Memantine (5 mg daily) Ketamine (25 100 mg BID) oral (compounded) Orphenadrine (100 mg BID) Serotonin-norepinephrine reuptake inhibitors (SNRIs) Venlafaxine Control Centralized mediators Minocycline Metformin Naltrexone Pentoxyfylline Alendronate Suppress or attenuate the microglial cells 5
Control Centralized mediators Stimulants Catecholamines (especially norepinephrine) play a role in the inhibition of descending pain signals Potentiate function of opioids and aspirin Caffeine Amphetamines Modanifil Functions Analgesia or pain modulation (suppress microglial cells, maintain analgesia receptors, mediate receptor binding) Neuroprotection of CNS cells (maintain BBB, prevent apoptosis) Neurogenesis (promote growth of damaged neurons and glial cells) Produced in the CNS without peripheral gland control Progesterone and Allopregnanolone Dehydroepiandrosterone Pregnenolone Estradiol and Estrogens Testosterone Human Growth Hormone Human Chorionic Gonadotropin (HCG) Oxytocin Symptoms of deficiencies noted may include hyperalgesia, allodynia, depression, insomnia, or poor pain control 6
Consider testing in patients with chronic pain (morning specimen) ACTH Cortisol Pregnenolone Testosterone Testosterone functions in the chronic pain patient Opioid receptor binding Dopamine-norepinephrine activity Maintenance of blood-brain barrier Androgenic-healing/tissue growth Libido Erectile activity (males) Maintenance of muscle and bone mass Exercise tolerance Testing & Replacement Follow labs Follow for side effects Female dosing ~25% of males 7
Testosterone replacement with precursors HCG (500-1000 units 2x/week) Dehydroepiandrosterone (DHEA 50-100 mg daily) Pregnenolone (50-100 mg daily) Androstenedione (50-100 mg daily) Medroxyprogesterone (10-20 mg daily) Injectable options Corticosteroids (joint pain, systemic) Platelet rich plasma / Prolotherapy Ketamine (NMDA receptor antagonist) (+/- studies) Botulinum toxin Cannabis for pain control Cannaboid receptors CB1 - more pervasive throughout the body, with particular predilection to nociceptive areas of the central nervous system and spinal cord CB2 - confined to lymphoid and immune tissues, is also proving to be an important mediator for suppressing both pain and inflammatory processes Look for high CBD:THC ratios to minimize high / intoxication effects Positive trials in neuropathic pain (Canadian studies) with NNT to decrease chronic pain by 30% was 5.6 8
References / Further reading https://www.practicalpainmanagement.com/treatments/complementary https://www.practicalpainmanagement.com/treatments/pharmacological/nonopioids https://www.practicalpainmanagement.com/treatments/hormonetherapy/hormone-testing-replacement-pain-patients-made-simple Russo EB. Cannabinoids in the management of difficult to treat pain. Therapeutics and Clinical Risk Management. 2008;4(1):245-259. 9