Targeting TRPV1 for analgesic effect Transient receptor potential vanilloid 1 (TRPV1) is the modern designation for the long-sought hypothetical pharmacological receptor for the pungent constituent of chili peppers, capsaicin, located on pain sensory nerve endings. It is a calcium-permeable ion channel best known for its ability to be gated by capsaicin David Julius (The Nobel Prize in Physiology or Medicine 2021) utilized capsaicin, to identify a sensor that responds to heat.

1. PRESENTED BY
ALLSUN SWEETLINE.M.S

2. Contributions
& Discovery
Role of TRPV1
in Dental Pain
Actions of
Capsicin
Unveiling TRPV1
as a Drug Target
01
02
04
05
03
Evidence of TRPV1
in Tooth
06
Conclusion
07
Recent
Researches

3. Transient receptor potential vanilloid 1 (TRPV1)
is the modern designation for the long-sought
hypothetical pharmacological receptor for the
pungent constituent of chili peppers, capsaicin,
located on pain sensory nerve endings.
It is a calcium-permeable ion channel best
known for its ability to be gated by capsaicin

4. DISCOVERY
CONTRIBUTION &
01

5. René
Descartes
Depicted that
particles of fire pulled
a thread between the
skin and brain
C.Golgi &
Santiago R.Y Cajal
Gave anatomical
description of the
Somatosensory
system
J. Erlanger and
H.S.Gasser
Discovered differentiated
functions of single
somatosensory nerve
fibers.

6. OF RECEPTOR?
NATURE
WHAT IS THE

7. David Julius (The Nobel
Prize in Physiology or
Medicine 2021) utilized
capsaicin, to identify a
sensor that responds to
heat.

8. CAPSAICIN
ACTION OF
02

13. IN TOOTH
EVIDENCE OF TRPV1
03

14. Immunoelectron microscopy
revealed expression of TRPV1,
TRPV2 and TRPV3 in
odontoblastic processes,
mitochondria and endoplasmic
reticulum

15. Expression of TRPV1
mRNA and protein has
been reported in human
dental pulp fibroblasts
cultured from the pulp
of third molar teeth

16. TRPV1 immunoreactivity has
also been detected in the
dental pulp nerve fibers of
the human permanent teeth.
Immunoreactivity is
significantly increased in
carious teeth compared with
non-carious teeth

17. TRP channels expressed in
odontoblasts might play a central
role in detection of hydrostatic
pressure within pulp

18. IN DENTAL PAIN
ROLE OF TRPV1
04

19. Thermal stimulation on the
tooth surface
Induce fluid movement in
the dentinal tubules
(Hydrodynamic theory)
Change in temperature in
the dentin
Exert mechanical stresses on the odontoblasts as
well as on the pulpal tissues.
Directly activate the mechanosensitive TRP channels nerve fibers
A temperature gradient
between the enamel and
dentine is observed
Tooth structures
expand or contract

21. AS DRUG TARGET
UNVELING TRPV1
05

22. choosing TRPV1?
is the need for
What

24. INHIBIT
HOW TO
TRPV1?

25. Two methods aimed at blocking TRPV1 in
diseases have been pursued as potential
treatment options.
1. Activation and desensitization of TRPV1 by
agonists.
2. Use of antagonist drugs for TRPV1 receptor.

26. Another critical feature that is desirable in
TRPV1 antagonists is its brain-penetration.
The antagonists that penetrate the brain
shows more analgesic efficacy than the
ones whose actions are limited to the
periphery.

27. TRPV1 agonists and antagonists have
been demonstrated to be beneficial in
different preclinical models of pain
associated with
 Dental pain
 Multiple forms of arthritis
 Cancer and chemotherapy
 Diabetic peripheral neuropathy
 Herpes zoster infection

28. COMPOUND COMPANY
THERAPEUTIC
INDICATIONS
DEVELOPMENTAL
STAGE(STATUS)
DWP-05195
Daewoong
Pharm
Oral treatment of Neuropathic
pain (post-herpetic neuralgia)
Phase I/II
ABT-102
ABT-116
ABT-443
Abbott
Pain associated with
inflammation, tissue injury and
ischemia
Phase I
Discovery
Discovery
PHE377 PharmEste
Diabetic Neuropathic pain and
post-herpetic neuralgia
Phase I (ongoing)
SB-705498
GlaxoSmithKli
ne Rhinitis
Chronic cough and Pruritus
Phase II migraine and
rectal pain
(terminated) Phase II
non-allergic rhinitis
(intranasal, ongoing)
MR-1817 Mochida Oral treatment of pain Phase I

29. Hyperthermia was a major side effect
encountered following administration
of TRPV1 antagonists in humans

30. RESEARCHES
RECENT
06

31. Clinical use of Ephedra herb
has not reported Hypothermia.
Therefore, it is possible that
Ephedra herb extract is more
effective than other TRPV1
antagonists in addressing acute
and chronic pain.

32. Lázaro. et al. identified Omega-9 fatty
acid as a new and natural inhibitor of
TRPV1 and provide a basis for
understanding its effects on reducing
both pain and itch.

33. A mouse model with a
gain-of-function
mutation in TRPV1
gene, wherein the pain
is impaired due to
reduced membrane
localization of TRPV1.

34. CONCLUSION
07

35. TRPV1 antagonists may represent the first
mechanistically novel class of analgesic drugs for many
years.
The TRP channels may serve as potential drug targets
for the development of pharmacological strategies to
manage dental pain.
However, the full adoption of TRPV1 antagonists into
clinical practice would depend on the development of
effective measures to counter drug-induced
hyperthermia.

36. References
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Physiology. Jaypee
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37. 6. Paul A. Moore(2018), Innovations in Local Anesthesia are Easing the Pain of
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local-anesthesia-are-easing-the-pain-of-dentistry
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capsaicin-induced pain. J Nat Med 71, 105–113 (2017).
https://doi.org/10.1007/s11418-016-1034-9
8. Morales-Lázaro, S., Llorente, I., Sierra-Ramírez, F. et al. Inhibition of TRPV1
channels by a naturally occurring omega-9 fatty acid reduces pain and
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products in the treatment of pain. Chemico-Biological Interactions. 330.
10.1016/j.cbi.2020.109178.
10. Schuh CMAP, Benso B and Aguayo S (2019) Potential Novel Strategies for the
Treatment of Dental Pulp-Derived Pain: Pharmacological Approaches and
Beyond. Front. Pharmacol. 10:1068. doi: 10.3389/fphar.2019.01068
References

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