The document discusses the use of a trp-pain blocker, derived from spices and herbs, for relieving acute shoulder pain due to bursitis, detailing a personal experience with its application and effects. It highlights the role of transient receptor potential (trp) channels in pain perception and the limitations of current pharmaceutical pain blockers that failed in clinical trials. The author emphasizes the potential of natural phytochemicals as effective alternatives for pain management, supporting the notion that 'food is medicine.'

1. SHOULDER PAIN RELIEF
WITH
TRP-PAIN BLOCKER
By
Kevin KF Ng MD, PhD.
Former Associate Professor of Medicine
Division of Clinical Pharmacology
University of Miami, Miami, F L., USA
Email: kevinng68@gmail.com
A Slide Presentation for HealthCare Providers Aug 2023

2. Acute Shoulder Pain Due to Bursitis: Aug 13, 2023
Pain

3. Timeline of shoulder pain treated with ion channel
“TRP-Pain Blocker” on Aug 13, 2023
A Personal experience
▪ 8.30 AM: I fried with my right hand 8 oz. onions, 6 eggs without yolk, 8
oz oyster mushrooms, and 8 oz flounder with a stainless spatula turner
in a wok. The process involved repetitively turning each ingredient over
a period of 2 to 5 minutes for a total of 15 minutes.
▪ 12.30 PM: Aching and throbbing pain occurred on my right shoulder with
a pain of 7 out of 10. The pain was accompanied by crepitus on
abduction and the shoulder was warm and tender to touch. These signs
and symptoms were suggestive of shoulder bursitis
▪ 2.30 PM: I applied 4 drops of TRP-Pain Blocker꭛ on the shoulder and
strongly rubbed them around the joint.
▪ 2.45 PM: I was pain-free and the joint has regained full range of motion
꭛TRP-Pain BlockerTM
is a blend of extracts of black pepper, ginger, turmeric, and mint

4. Preparation of a liniment from spices and herbs
Extraction Essential oil
▪ Distillation ▪ Black pepper oil Carrier oil Liniment
▪ Microwave ▪ Ginger oil
▪ Turmeric oil
▪ Mint oil

5. Actions of selected phytochemicals on TRP ion channels
Ion channel

6. Pain Reduction by a single or a combination of
spices and herbs

7. DISCOVERIES OF
▪ TRANSIENT RECEPTOR POTENTIAL (TRP) CHANNELS
▪ NOCICEPTIVE RECEPTOR
▪ NOCICEPTIVE NERVE FIBER

8. https://www.youtube.com/watch?app=desktop&v=64x74JO7c9k

9. Discoveries of nociceptive receptors
▪ Nociceptive Receptors Discovery:
▪ knowledge of temperature and touch receptors led to the identification of nociceptive receptors,
also known as nociceptors.
▪ Nociceptors are specialized sensory nerve endings that respond to intense mechanical, thermal, or
chemical stimuli associated with tissue damage. They are responsible for transmitting signals that
result in the perception of pain.
▪ Types of Nociceptors:
▪ nociceptors also come in different subtypes. For example, mechanical nociceptors respond to
strong mechanical forces, thermal nociceptors respond to extreme temperatures, and chemical
nociceptors respond to specific chemical irritants released during tissue damage or inflammation.
▪ Two different types of axons.
▪ The first is the Aδ fiber axons. They are myelinated and can allow an action potential to travel at a
rate of about 20 meters/second toward the CNS.
▪ The other type is the more slowly conducting C fiber axons. These only conduct at speeds of
around 2 meters/second. This is due to the light or non-myelination of the axon.

10. The Primary Afferent Nerve Fiber – Where Pain Signals begin
https://www.youtube.com/watch?v=a5b9-_UQEzI

11. Release of nociceptive mediators from
neurogenic inflammation
https://www.youtube.com/watch?v=a5b9-_UQEzI

12. Discovery of capsaicin receptor (TRPV1)
https://www.youtube.com/watch?v=a5b9-_UQEzI

13. Discoveries of TRP Channels:
convergent targets for natural irritants (2021)
https://www.youtube.com/watch?v=a5b9-_UQEzI
TRPM8
TRPV1
TRPA1

14. What is an ion channel?
Adapted from https://www.genetex.com/Research/Overview/neuroscience/Ion-Channels
Ion channels are proteins located on the plasma membrane of the sensory nerve fiber

15. Classification of ion channels
https://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=78
• 300 different ion channels
• 13 superfamilies
• 6 TRP subfamilies
• Only TRPV1 and TRPA1 are
widely studied for pain, cold,
and itch
6 TRP subfamilies
Pain
Pain

16. The functions of TRPA1 ion channel (2022)
▪ TRPA1 is an ion channel located on the plasma
membrane of many human and animal cells.
▪ It is a sensor for pain, cold, itch, and
environmental irritants.
▪ TRPA1 is activated by a number of
▪ reactive compounds:
▪ allyl isothiocyanate, cinnamaldehyde, farnesyl thiosalicylic
acid, formalin, hydrogen peroxide, 4-hydroxynonenal,
acrolein, and tear gases
▪ and non-reactive compounds (nicotine, PF-4840154[16])
and is thus considered as a "chemosensor" in the body.
▪ TRPA1 is co-expressed with TRPV1 on nociceptive
primary afferent C-fibers in humans.
▪ TRPA1 is considered the final pathway for pain
perception and a target for intense research
https://www.moleculardevices.com/applications/ion-channels
Final pathway for pain perception

17. What is an ion channel, TRP-Pain Blocker?

18. Additional pharmacological actions of Phytochemicals
• Ant-inflammatory
• Immuno-modulatory

19. MECHANISM OF PAIN RELIEF
BY
BLOCKING TRPA1 ION CHANNEL

20. Diagram of pain pathways involved in pain
transmission and modulation (2013)
Gene Therapy for Chronic Pain Management
http://dx.doi.org/10.5772/5505

21. Pain Perception and Dermal Nerve Plexus of
Human Skin
https://www.sciencedirect.com/scienc
e/article/pii/S0022202X15305935#f
0015
Gene Therapy for Chronic Pain Management
http://dx.doi.org/10.5772/5505

22. Functional Anatomy of Sensory Fiber and Nociceptors (2010)
https://www.researchgate.net/publication/265425188_Functional_Anatomy_of_Muscle_Muscle_Nociceptors_and_Afferent_Fibers
Afferent nerve endings Neuropeptides (SP, CGRP)

23. This is how a nerve ending looks.
It has been broken open to reveal vesicles (orange and blue) containing chemicals used
to pass messages in the nervous system (2020)
Principles of Neural Science (Principles of Neural Science (Kandel)) 5th Edition

24. Release of neuropeptides in neurogenic pain perception
https://www.researchgate.net/figure/9-Events-occurring-around-a-muscle-
nociceptor-during-noxious-mechanical-stimulation-The_fig4_265425188

25. The release of neuropeptides in Inflammatory pain perception(2012)
https://www.researchgate.net/figure/Neuronal-factors-released-from-nociceptor-sensory-neurons-directly-drive-leukocyte_fig4_230573679
SP
CGRP
1. Neurogenic
inflammation
2. Vasodilation
4. Pain sensation
3. Immune-
mediated
inflammation

26. Substance P (SP) and Calcitonin gene-related peptide (CGRP)
▪ Substance P (SP):
▪ It is primarily released by sensory nerve fibers
▪ It is released in response to inflammation, tissue
injury, and nerve stimulation.
▪ It is involved in neurogenic inflammation, where it
contributes to vasodilation, plasma extravasation,
and the recruitment of immune cells to the site of
inflammation.
▪ It is considered to be a "universal" mediator of
inflammation.
▪ Calcitonin gene-related peptide (CGRP):
▪ It is released by sensory nerves as well as other
cell types, such as mast cells, macrophages, and
endothelial cells.
▪ Its release is also stimulated by inflammation,
nerve stimulation, and certain cytokines.
▪ CGRP is involved in vasodilation, modulation of
immune responses, and sensory neuron
sensitization.

27. Chemical mediators of inflammation released by
trauma, infection and chemicals
Stimuli
• Injury
• Infection
• Chemical
Source
• Tissue cells
• Immune cells
• Endothelium
• Nerves
• Fibroblasts
• Plasma
Mediators
• Histamine
• Serotonin
• Prostaglandins
• Leukotrienes
• Platelet activating
factor
• Nitric oxide
• Bradykinin
• Cytokines
• Chemokines
• Neuropeptides
• SP
• CGRP
©DRKKFNG

28. Targets of Nociceptive Mediators on Intra-epidermal
free nerve endings (2020)
https://www.researchgate.net/figure/Epidermal-keratinocytes-modulate-
nociceptive-sensory-neuron-activity-Keratinocytes_fig2_338457032

29. Receptors for pain stimuli in sensory nerve endings
https://www.news-medical.net/whitepaper/20190817/Ion-Channels-Involved-in-Pain.aspx

30. Pain perception induced by mediators from
intense exercise, infection, and chemicals
PAIN
©DRKKFNG

31. The current strategy to treat somatic pain:
anti-inflammatory drugs
PAIN
• Aspirin blocks the generation of prostaglandins
• Diphenhydramine blocks the action of histamine
• Many other inflammatory mediators are unopposed ©DRKKFNG
Current drugs do not block all mediators Synthetic and natural blockers
?

32. List of Pharmaceutical Companies that hold patents for
TRPA1 antagonists/blockers
▪ In the last three decades, 14 organizations published 28 patent
applications disclosing potential uses of TRPA1 antagonists.
▪ 5 have been evaluated by clinical trials.
▪ None had passed beyond Phase II trials.
▪ The major pharmaceutical companies are:
1. AstraZeneca
2. Pfizer
3. Merck & Co.
4. Sanofi
5. Novartis
6. GlaxoSmithKline (GSK)
7. Johnson & Johnson
8. AbbVie
9. Eli Lilly and Company
10. Boehringer Ingelheim
https://www.tandfonline.com/doi/abs/10.1080/13543776.2020.1797679?journalCode=ietp20

33. Looking ahead to the future of
Topical Pain Management:
PAIN
×
Inhibition of activation of ion channels renders a wide-spectrum blockade
©DRKKFNG
TRP Pain Blockers: phytochemicals
×

34. List of Some Natural TRP-Pain Blockers/Antagonists
×

35. The evidence of anti-inflammatory and analgesic
effects of phytochemicals on pain perception
show that Food is Medicine
▪ Nociceptive pain:
▪ Soft tissue injuries
▪ Post-surgical pain
▪ Radiation dermatitis
▪ Low back pain
▪ Inflammatory pain:
▪ Fire ant stings
▪ Wasp stings
▪ Yellow jacket stings
▪ Mosquito bites
▪ Medical conditions
▪ Itch in psoriasis
▪ Arthritis pain
▪ Diabetic neuropathy
▪ Gouty arthritis
▪ Migraine headache
▪ Menstrual cramps

36. Summary
▪ Nociceptive Transient Receptor Potential ion channels
(TRPV1, TRPA1) were discovered by D. Julius and A.
Patapoutian who were jointly awarded the Nobel Prize in
Physiology or Medicine in 2021.
▪ Activation of these ion channels induced pain perception.
Blockade of these channels attenuated pain perception.
▪ About 28 synthetic blockers had been patented by 14
Pharmaceutical companies. None had been successfully
tested in clinical trials.
▪ This simple experiment using extracts from spices and
herbs provides evidence that food is medicine.