Pain Management:

Non-Opioid Treatments

Learning Objectives

1. Recognize appropriate patient recommendations and explanations for non-prescription

treatment options including herbal, supplement, vitamin, antihistamine, topical, and stimulant.
2. Select appropriate patient recommendations and explanations for non-opioid prescription
treatment options including botulinum toxin, antihistamine, transdermal, and topical
medications.
3. Differentiate NSAIDs based on structural class, individual characteristics, unique side effects, and
anticipated drug-drug interactions.
 Herbals & Supplements
Anti-inflammatory Properties

White Willow Bark

• Salicin
• Metabolized salicylic
Wintergreen acid
• Contains methyl
salicylate
Peppermint
• Menthol derived from
• Inhibits Sodium (Na)
channels

Caution: Drug Interactions

 Herbals & Supplements
Anti-inflammatory Properties

Aquamin
Boswellia (Frankincense Extracted from)
Wild, Sweet, Winter, & Sour Cherries
Ginger
Ginseng (American, Panax/Asian, or Siberian)
Kava Kava
Valerian Root
St. John’s Wort
Devil’s Claw
Vitamin B & Vitamin D
o Low Vitamin B/D levels lead to increased pain & decreased immunity
Caution: Drug Interactions
 L-methylfolate

Serotonin (5HT)
Folate (Natural)
Dihydrofolate Tetrahydrofolate L-methylfolate Norepinephrine
or Folic Acid MTHFR BBB
(DHF) (THF) (Bioactive) (NE) Dopamine
(Synthetic)
(DA)

L-Methylfolate Product ~ Pricing

(90)

Rx 15mg (Deplin®, etc.) $200-$500

Rx 7.5mg (Deplin®, etc.) $100-$500

Rx 3mg (Metanx®, etc.) $75-$225

Non-FDA Approved Supplements 1-5mg $12-$60

 Emu Products
Observed Uses (MOAs)
 Arthritis (Omega-3, Omega-6, & Omega-9)
• Hypocholesterolemic Effect (Omega-3, Omega-6, & Omega-9)
• Mucositis (Omega-3, Omega-6, & Omega-9)
• Irritable Bowel Disease (Omega-3, Omega-6, & Omega-9)
• Cancer Chemotherapy Induced Bone Loss (TNF-alpha, RANK, etc.)
• Hair Loss (Omega-3, Omega-6, & Omega-9)
• Mosquito Repellant (Effective for ~30 Minutes)
 Antihistamines

• Histamine promotes pain “transmission”

• Antihistamines have very little evidence of analgesia or

dose-sparing effects

o Commonly used for analgesia of bone pain

associated with chemo-induced neutropenia

o Promethazine commonly used as an adjunct to

opioids post-operatively
 Stimulants

Amphetamine Products
• Controversial, Overstimulation of D/NE
• Similar MOA in ADHD treatment
 Stimulants

Caffeine
Product Caffeine
• 1980’s Studies showed 40% Efficacy of APAP (~mg)
12oz. Starbucks® Cup of Joe 250
• Other studies showed adjunctive Cup of Decaf Joe 5

enhanced/prolonged effect with other analgesics Espresso (shot) 40

8oz. Black Tea 50
• Possible MOAs: 8oz. Green Tea 25

12oz. Can of Soda 40-50

(FDA Max 71)
• Block Adenosine Receptors?
8oz. Red Bull® 80
1.5oz Dark Chocolate 30
• COX-2 Inhibition? 1.5oz Milk Chocolate 10
Hot Cocoa 10

• or simply by affecting one’s mood

 Botulinum Toxins

• Botulinum toxin is a neurotoxin which is produced by the Gram-positive anaerobic bacteria

Clostridium botulinum which causes Botulism, a disease that is characterized by potentially
life-threatening neuroparalysis
• There are seven distinct serotypes of Botulinum toxin : A, B, C1, D, E, F, and G
• Human botulism is caused mainly by types A, B, E, and (rarely) F
• 1989: FDA approves BOTOX® for strabismus (crossed eyes) & blepharospasm (twitching
eyelids)
• 2000: FDA approves BOTOX® for head & neck spasms

Al-Ghamdi AS, et al. Botulinum Toxin: Non Cosmetic & Off-Label Dermatological Uses. J Derm & Derm Surg 19 (2015) 1-8.
 Botulinum Toxins

Products
o ONAbotulinumtoxinA (Botox®)
 100 Unit & 200 Unit Vials
o ABObotulinumtoxinA (Dysport®)
 300 Unit & 500 Unit Vials
o INCObotulinumtoxinA (Xeomin®)
 50 Unit & 100 Unit Vials
o RIMAbotulinumtoxinB (Myobloc®)
 2,500 U/mL, 5,000 U/mL, & 10,000 U/mL Vials

Typical Treatments
• Muscle Stiffness (Neck, elbow, wrist, & fingers)
• Headaches
 Lidocaine
Transdermal Treatments
Lidocaine Mechanism of Action (MOA): Decreases frequency (not duration) of Na Channel opening

Prescription (Rx)
 Lidocaine 5% Patch (Lidoderm®)
o Up to 3 patches, 12 hours on & 12 hours off
o 40% Released in 1st Hour, then will release for almost 5 days

Over-The-Counter (OTC)
 Lidocaine 4% Patches
o Icy/Hot® (+ Menthol): Apply 1 patch up to every 12 hours
 Lidocaine
Transdermal Treatments

Over-The-Counter (OTC)
o 0.5% to 5.0%
o Dentinox, Jogel, Doxiproct, etc …

Prescription (Rx)
o Lidocaine 5% Ointment
o Eutectic Mixture of Local Anesthetics (EMLA® Rx Cream)
 Lidocaine 2.5% & prilocaine 2.5% (25mg each per 1g)
 Apply with occlusion for 1-2 hours, remove, then pain relief lasts 1-2 hours
 Topical Treatments
Counterirritants
o MOA: Flood pain/touch sensory channels (TRP-V1/PA1/M8)
o Examples: Menthol, methyl salicylate, eucalyptus oil, turpentine oil, & camphor
o Products: Icy/Hot®

Capsaicin
o Found in hot chili peppers & depletes Substance P (pain transmission)
o OTC 0.025% & 0.075% Creams & Patches
 Topical Treatments

Topical NSAIDs
Patch Diclofenac epolamine 1.3%

Solution Diclofenac Sodium 1.5%

Gel Diclofenac Sodium 1% (Voltaren®)

Diclofenac sodium 5% (Diclac®)

Clinical Pharmacology Online Database. 2018.

 Topical Treatments
NSAIDs
Voltaren® Gel
• FDA Approved for osteoarthritis pain relief in joints (knees and hands)

• Dosing
o 2 g for each elbow, wrist, or hand
o 4 g for each knee, ankle, or foot
 Max Dose Per Day is 32g

• Penetration Enhancers
o Isopropyl alcohol, propylene glycol, and water

Novartis. 2009. Voltaren Gel Prescribing Information. http://www.voltarengel.com/common/pdf/Voltaren-PI-10-19.pdf

 NSAID Mechanisms of Action

Major Side Effects of NSAIDs & COX-2 Selective Inhibitors. March 2017. http://tmedweb.tulane.edu/pharmwiki/doku.php/nsaid_side_effects
 NSAID Mechanisms of Action

Major Side Effects of NSAIDs & COX-2 Selective Inhibitors. March 2017. http://tmedweb.tulane.edu/pharmwiki/doku.php/nsaid_side_effects
 NSAIDs
Non-Steroidal Anti-Inflammatory Drugs
NSAIDs inhibit prostaglandin biosynthesis by preventing arachidonic acid binding to
• Cyclooxygenase (COX) Enzymes 1 & 2
o Also known as Prostaglandin Endoperoxide Synthase 1 & 2
o Also known as prostaglandin G/H synthase 1 & 2

Cox-1
COX-1
• Expressed in nearly all cells but mainly functioning in the GI tract, kidneys, & platelets
• Produces thromboxane & prostacyclin in equal amounts, maintaining a balance
COX-2
• Expressed in the brain, kidneys, & blood vessels (i.e. the areas most susceptible to Cox-2

thrombotic events)
• Expression of COX-2 can be induced by cytokine release due to injury or inflammation
 NSAID Mechanisms of Action

COX-1 Inhibitors COX-2 Inhibitors

Pros Pros
• Inhibits production of thromboxane • More specific to prostaglandins
➢Less Cardio issues (MI/stroke) ➢Less GI issues (Less ulcers & bleeds)
Cons Cons
• Affects GI mucosa • Inhibits production of prostacyclin
➢Peptic ulcers/GI bleeding ➢More Cardio concerns (MI/Stroke)

Feldman M & McMahon A. Do Cyclooxygenase-2 Inhibitors Provide Benefits Similar to Those of Traditional Nonsteroidal Anti-Inflammatory Drugs, with Less Gastrointestinal Toxicity? Ann Intern Med. 2000;132:134-143.
 NSAID Mechanisms of Action

COX-1 Selective COX-2 Selective

Feldman M & McMahon A. Do Cyclooxygenase-2 Inhibitors Provide Benefits Similar to Those of Traditional Nonsteroidal Anti-Inflammatory Drugs, with Less Gastrointestinal Toxicity?
Ann Intern Med. 2000;132:134-143.
The 4 A’s of Cox Inhibition

1. Anti-inflammatory (reduces inflammation)

2. Antipyretic effect (reduces fever)
3. Antithrombotic effect (reduces platelet
stroke risk)
4. Analgesic effects (reduces pain)