Delayed onset muscle soreness (DOMS) is caused by microscopic damage to muscle fibers following unaccustomed exercise. It causes pain and stiffness in the hours to days after exercise. The document discusses the inflammatory process underlying DOMS and how certain phytochemicals found in foods and herbs may help relieve symptoms by targeting inflammatory mediators. A clinical study showed that a topical formula containing phytochemical extracts from spices and herbs effectively reduced pain and swelling in patients with muscle injuries like strains or sprains.

1. DELAYED ONSET OF
MUSCLE SORENESS (DOMS):
RELIEF BY TOPICAL
NATURAL PHYTOCHEMICALS
By
Kevin KF Ng, MD, PhD
Former Associate Professor of Medicine
Division of Clinical Pharmacology
University of Miami, Miami, Florida, USA
Email: kevinng68@gmail.com
A slide presentation for HealthCare Provider Seminar Nov. 2018

2. Lecture outline
▪ Definition of delayed onset muscle soreness (DOMS).
▪ Clinical features: Time course, signs and symptoms, imaging,
inflammation markers, histology of microtrauma in muscles.
▪ Physiology of Inflammation and resolution: pro-inflammatory and
specialised pro-resolution mediators (SPM)
▪ Phytochemicals: sources, extraction, molecular targets.
▪ Clinical effects of phytochemicals in massage oils on pain and
swelling.
▪ Summary.

3. What is Delayed Onset Muscle Soreness (DOMS) ?
▪ Delayed onset muscle soreness (DOMS) also called
muscle fever is the pain and stiffness felt in muscles
several hours to days after unaccustomed or
strenuous exercise.
▪ It is caused by eccentric (lengthening) exercise,
which causes small-scale damage (microtrauma) to
the muscle fibers.
▪ It is classified as Type 1 muscle strain.
▪ https://en.wikipedia.org/wiki/Delayed_onset_muscle_soreness

4. Timeline of Delayed Onset Muscle Soreness
Delayed onset:
▪ start from 8 to 12 hour
▪ peak from 24 to 48 hour
▪ last 96 hours
https://nikmcomber.wordpress.com/2014/04/07/04-april-2014-friday/

5. Graphic structure of a muscle fibre
https://www.intechopen.com/books/regenerative-medicine-and-tissue-
engineering/skeletal-muscle-regeneration-for-clinical-application
http://thelabfitness.club/articles/doms

6. Capillaries of skeletal muscle
http://histonano.com/books/Junqueira%27s%20Basic%20Histology%20PDF%20WHOLE%20BOOK/10.%20Muscle%20Tissue.htm
Capillaries

7. Microscopy of muscle fiber, blood vessel, WBC and Mast cell
containing Histamine
https://www.ncbi.nlm.nih.gov/pubmed/25062998
Mast cell
Mast cell
WBC

8. Signs and Symptoms of Delayed Onset Muscle Soreness
▪ Dull aching pain in affected muscles
▪ Swelling in affected muscles
▪ Tenderness and stiffness in affected
muscles
▪ Muscular mechanical hyperalgesia
▪ Reduced muscle performance
https://truthofbuildingmuscle.com/what-is-delayed-onset-muscle-soreness-doms-for-short

9. Thermal evaluation of muscle temperature:
Heel Toe technique shows areas of increased muscle temperature
At rest After 10 min playing After 20 min playing
http://article.sapub.org/10.5923.j.scit.20110101.01.html

10. Necrotic skeletal muscle
http://neuromuscular.wustl.edu/pathol/necrosis.htm
leukocyte infiltration
necrotic skeletal muscle

11. Transmission electron microscopy image from control muscle and
biopsies taken 48 h after stimulated isometric contractions
showing different grades of disruption to muscle morphology:
mild disruption (+), major disruption (++), and destruction (+++) of z-line
Abigail L. Mackey et al. J Appl Physiol 2008;105:1620-1627
mild disruption (+) major disruption (++) destruction (+++) of z-linecontrol

12. Is Inflammation the Cause of Delayed Onset Muscle Soreness ?
Evidence against inflammation
▪ No significant increase in
inflammatory markers
▪ Self-limiting disorder
Evidence in favor of inflammation
▪ Pain
▪ Swelling
▪ Loss of function
▪ Microscopic tissue damage
▪ Increase of neutrophils &
macrophages
▪ Increase of muscle damage CPK
▪ Mild response to NSAIDS

13. Clinical Feature of DOMS are suggestive of Inflammation
▪ Microscopy of DOMS muscle: ● increased (1) neutrophils and (2) macrophages
● necrosis in muscles
▪ Blood Tests: ●increased white cell count
●increased muscle CPK (creatine phosphokinase)
●other inflammatory markers increase ?
▪ Infrared thermogram: elevated tissue temperature
▪ Moderate pharmacologic response to COX-2 inhibitors
https://brage.bibsys.no/xmlui/bitstream/handle/11250/171319/Paulsen%202009%20ikke%20paper%20III-IV.pdf?sequence=5

15. Pain Swelling Heat Redness
The body’s immune response to tissue injury

16. Purpose and Events in Acute Inflammation
To prepare the damaged tissues for repair and resolution:
1. Coagulation (blood changes from a liquid to a gel)
2. Dilatation of blood vessels (vasodilation)
3. Exit of white blood cells (diapedes)
4. Release of pro-inflammatory chemical mediators
5 Actions of mediators on their respective receptors
6. Switch to release of pro-resolution chemical mediators (SPM)
7. Removal of dead cells and debris from damaged tissues (phagocytosis)
8. Return to homeostasis

17. Signs and symptoms of Inflammation
▪ Pain
▪ Swelling
▪ Redness
▪ Warmth
▪ Loss of Function
INFLAMMATION
(set on fire)
https://www.uu.se/en/about-uu/history/celsius/
A. Celsius 1710-1744
R. Virchow 1821-1902
A. Celsius
R. Virchow

18. Components of Inflammation
▪ Mast cell
▪ Macrophage
▪ Neutrophil (PMN)
▪ Lymphocyte
▪ Monocyte
▪ Eosinophil
▪ Basophil
▪ Platelet
▪ Plasma
▪ Fibroblast
▪ Endothelium
WBC
https://slideplayer.com/slide/8031830/

19. Role of Inflammatory cells
▪ Release of preformed mediators
▪ Release of enzyme induced mediators
▪ Actions of mediators on receptors
▪ Recruitment of new inflammatory cells
▪ Death of inflammatory cells
▪ Phagocytosis of debris and necrotic tisssue
https://slideplayer.com/slide/8031830/

20. Formation of a Blood Clot
https://www.pinterest.com/pin/335870084686282762/?lp=true https://medlineplus.gov/ency/imagepages/19462.htm

21. Vasodilation in a blood vessel
http://www.naturalhealthcarenutrition.com/blog/archives/03-2016

22. Movement of Leukocyte across blood vessel wall (endothelium):
Diapedesis
http://idamalonemicrojournal.blogspot.com/Source: Anthony L. Mescher: Junqueira’s Basic Histology, 14th Edition

24. Source of chemical mediators in Inflammation
results

25. Actions of inflammatory chemical mediators

26. Time-line showing the inflammatory response and resolution

27. Life span of white blood cells
https://www.slideshare.net/P-Z0-3/white-blood-cells-39413127

29. Time-line showing the inflammatory response and resolution
from pro-inflammatory to specialised pro-resolving lipid mediators

30. Mediators of inflammation and resolution

31. Lipid mediator class-switching from
Pro-inflammatory to Pro-resolving mediators
https://www.ahajournals.org/doi/pdf/10.1161/circresaha.116.307308

32. Origins and Functions of specialised pro-resolving mediators
Adapted from http://thetispharma.com/cms2/technology/lipid-biology/spm-tree/
Functions

33. Summary of Chemical mediators of the inflammatory response
https://www.hindawi.com/journals/iji/2013/985815/fig1/

34. Delayed-onset Muscle soreness and Differential leucocyte count
following calf-raise exercise
Muscle soreness

35. Time course in delayed onset of muscle soreness (DOMS) and WBC
following calf-raise exercise as determined by visual analogue scale (VAS)
NEUTROPHILS SORENESS
soreness
VAS (mm)

36. Chemical mediators that cause vasodilation and increased permeability

37. Chemical mediators that cause pain
▪ Histamine
▪ Bradykinin
▪ Prostglandin E₂
▪ Substance P
▪ Potassium
http://www.slideserve.com/hollis/somatic-sensations-ii-pain-headache-and-thermal-sensations

38. Why NSAIDS are not effective to relieve pain in DOMS?
▪ Can we use anti-inflammatory phytochemicals to block the chemical mediators?
diphenhydramine
Aspirin (NSAIDS)
drug

39. Many phytochemicals are known to have
anti-inflammatory properties

40. What are phytochemicals?
▪ Phytochemicals are bioactive compounds found in
roots, barks, stems, leaves, flowers and fruits of plants.
▪ Phytochemicals are secondary metabolites of plants.
▪ Phytochemical are beneficial for health.
▪ Phytochemicals are not vitamins.
▪ Phytochemicals may exert antimicrobial, antioxidant,
anti-inflammatory and anticancer actions

41. Broad Classification of Phytochemicals
https://www.semanticscholar.org/paper/Phytochemical-composition-of-nuts-CY-Chen-
Blumberg/a38cc62ab5ed594787638cc4613e22c23d690417

42. Functions of Phytochemicals
Plants
▪ Protections from microbes
and parasites.
▪ Color of plant products
▪ Anti-oxidant actions
▪ Hormonal actions
Human
▪ Ant-inflammatory
▪ Anti-oxidant
▪ Anti-cancer
▪ Anti-aging
▪ Anti-microbial

43. Rationale of Use of Topical Phytochemicals for DOMS
▪ Most phytochemicals are metabolized in the gastro-intestinal tract and liver.
▪ Most phytochemicals are soluble in oil.
▪ Olive oil and massage oils contain fatty acids (oleic acid, linoleic acid,
linolenic acid) which are easily absorbed through the skin..
▪ Phytochemicals in olive and massage oils are absorbed through skin
bypassing the portal circulation to optimize their pharmacological effects.
▪ Phytochemicals act on multiple targets and they act in synergy.

44. Common massage oils
▪ Sweet almond oil
▪ Grape seed oil
▪ Sunflower oil
▪ Olive oil
▪ Canola oil
▪ Flaxseed oil
▪ Wheatgerm oil
▪ Jojoba oil

45. Common massage oils & their composition:
oleic acid, linoleic acid, α-linolenic acid
▪ Sweet almond oil
▪ Grape seed oil
▪ Sunflower oil
▪ Olive oil
▪ Canola oil
▪ Flaxseed oil
▪ Wheatgerm oil
▪ Jojoba oil

46. Skin absorption rating of carrier oils
https://www.beneficialbotanicals.com/facts-figures/absorption-ratings.html
1: fastest
5: slowest

47. Functions of massage oils
▪ Act as carrier for phytochemicals.
▪ Reduce friction between hand of
the therapist and skin of the patient

48. Experimental methods
▪ Search for anti-inflammatory phytochemicals in food,
spices, herbs in PubMed
▪ Search for phytochemicals that block inflammatory
mediators: HMGB1, iL-1, iL-6, TNF-α, NF-kB, COX-2, 5-LOX,
iNOs, PGs, LTs, TXA₂, PAF, NO, histamine, serotonin, bradykinin,
substance P in spices and herbs
▪ Tabulation of chemical mediators against spices and herbs
▪ Extraction of bioactive compounds with different solvents and
massage oils
▪ Open clinical trials on patients
▪ Randomized controlled trials

49. Examples of anti-inflammatory phytochemicals
in food, spices and herbs
Product Variety Active ingredient
Fruit Grape Resveratrol
Apple Quercetin
Chili pepper Capsaicin
Leaf Green tea EGCG
Aloe Salicylic acid, emodin
Bark White willow Salicylic acid
Magnolia Honokiol
Root Ginseng Ginsenosides
Galagal Galagin
Tumeric Curcumin

50. Phytochemical Molecular Targets
Ginger
Aloe
Cayenne
Green tea
Lemon grass

51. Preparation of extracts of phytochemicals with
alcohol and olive oil
Botanical materials + extraction solvent
Temperature controlled treatment
Homogenization
Differential centrifugation
Residue removal
Recovery of filtrate

52. Effects of Phytochemicals on Inflammatory Mediators
Synergistic effects of extracts

53. A phytochemical formula L35 made from spices and herbs for
Pain, Itch and Swelling
chemical mediators
Spices
Herbs

54. Effects of L35 Formula on Pain & Swelling in Contusion, Strain and Sprain:
L35= blend of 5 spices and herbs in massage oil
10
5
2
1 1
10
8
5
3
2
0
2
4
6
8
10
12
onset 15 min 30 min 60 min 120 min
Scale
Time
pain swelling

55. Effects of Phytochemical extracts on DOMS

56. Conclusions
▪ Delayed onset of muscle soreness (DOMS) is the result of acute inflammation.
▪ Inflammation involves the release of chemical mediators from white blood cells,
plasma, blood vessel endothelium, and nerve endings.
▪ The chemical mediators acting on their receptors cause pain, swelling, redness and
warmth which are the cardinal signs of inflammation.
▪ Inflammation is normally followed by resolution which is orchestrated by switching
pro-inflammatory mediators to pro-resolving mediators.
▪ Phytochemical extracts in massage oils reduce pain and swelling by targeting
multiple inflammatory mediators.
▪ Evidence in this study shows that anti-inflammatory phytochemicals from spices and
herbs are effective in relieving pain and soreness in DOMS

57. ANY QUESTION?
Please contact
Kevin KF Ng, MD, PhD
Email: kevinng68@gmail.com