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Full hair regrowth (benoxaprofen and sulfasalazine arthritis drugs)


#1

This is a new thread to discuss 3 cases in which it seems rheumatroid arthritis drugs restored hair.

What is interesting about these 3 cases is that:

  1. growth of hairs was over an area of scalp that he
    previously been devoid of visible hair

  2. and the new density of new hair growth on the
    scalp was equal to that on the areas of his scalp that were not subject to
    balding.

  3. They were male pattern baldness sufferers

this is something that sounds like a complete cure. The ultimate goal we are after. And its been done 3 times on humans. Noone else acheived anything even margnaly close to this.

First two cases are on benoxaprofen.

Third is recent report of hlh user who reported that he regrew 3cm of slick bald frontal hairline loss to full density and teen like coverage while he was taking sulfasalazine.

The timeline for these incidents were 5-9 months of continuous oral drug intake to see the regrowth. The dosages of sulfasalazine was 3000mg a day.

I already posted 2 related threads where more information can be found:

benoxaprofen: http://www.hairsite.com/hair-loss/forum_entry-id-32535-page-0-category-1-order-last_answer.html

sulfasalazine and benoxaprofen: http://www.hairsite.com/hair-loss/board_entry-id-84934.html

Bellow here is a summary of my findings so far:

Both benoxaprofen an sulfasalazine have few things in common.

One is for almost sure. The drugs alone wont grow hair. I concluded this from the fact that plenty of ppl take the drugs, so if hair growth was common side effect, they would have noticed. The ultimate goal of this thread would be to find out what is the missing part that together with these drugs gave the users the pleasant side effect.

They have similar side effects (photosensitivity for example). Both are anti inflamatory drugs used to treat rheumatoic arthritis and similar diseases.

Theres also a study that says that misture of iron ions together with 5-aminolevulinic-acid 5ala (active component in sulfasalazine) grows hair in mice

And patent that shows growth in humans (although its not sure if these were male pattern baldness cases at all):

http://www.google.com/patents?hl=cs&lr=&vid=USPATAPP11568322&id=oE2iAAAAEBAJ&oi=fnd&dq=5-aminolevulinic+acid+"male+pattern"&printsec=abstract#v=onepage&q=5-aminolevulinic%20acid%20"male%20pattern"&f=false

The regrowth in the patent is unusualy fast (4-7 weeks).

There is some minor evidence that arthritis has to do with some lack of some bone progenitor cells (and we know that hairloss has to do with lack of hair follicle progenitor cells as well)

http://scholar.google.com/scholar?q=progenitor+arthritis

Sulfasalazine is also used to reverse fibrosis.

http://www.gastrojournal.org/article/S0016-5085(04)01847-5/abstract?referrer=http://scholar.google.cz/scholar?q=sulfasalazine+fibrosis&hl=cs&btnG=Hledat

We also speculated that it could be sunburn (the photosensitivity damage) + the drug that stimulates the new growth.

This is very weak hypothesis. To support it we only have a gefinitib guy case which somehow shows regrowth on areas exposed to sun (if he got sunburn from back to front). All in all, i consider this to be just speculation.

http://www.hairsite.com/hair-loss/forum_entry-id-33436.html

Although it should also be stated that the patent also suggests that opposite can be acheived (if too much of 5-ala together with photo stimulation is used, follicles can be damaged).

If we were to try topical mixture of 5-ala and iron ions or mixture based on the patents, we should probably first test it on areas where possible hairloss wont bother us (very back of our neck for example) to find out if its safe. Also both users of anti androgens and users who do not use antiandrogens at all should try to test this, because atm we dont know if that can interfere with the treatment.

Im sick of this disease. Lets try to crack this down.

Everyone who can contribute please do so. Everyone who knows anyone who is scientificaly interested or knows any hair loss site user who is especialy bright in science of hairloss, please notify them of this thread.


#2

acne is another androgen triggered disease.

5-ala together with phototherapy is used to treat this disease:
http://www.google.com/books?hl=cs&lr=&id=sCDBBoVhrPQC&oi=fnd&pg=PA31&ots=oOQQmG8xWD&sig=gQ8fufnFrNaN-XPmiJmevm64gLQ#v=onepage&q&f=false

One interesting idea would be to use hair growing lasers together with 5-ala as photosensitiser.

Again, users who would be willing to test this should be cautious and first try it on areas where opposite effect (hair depilation) wont bother them.


#3

#4

» http://en.wikipedia.org/wiki/Levulan

Strange Stuff, benefit of the doubt :slight_smile:


#5

Didn’t have time to read everything, but the “all but one patient had photosensitivity, and all hair growth was on areas exposed to the sun” quote caught my eye.

Perhaps skin disruption via sunburn is the common denominator. This sounds like the same phenomenon that the gefitinib patients experienced.

Perhaps this is another possible avenue for Follica’s wounding/disruption method?


#6

» This is a new thread to discuss 3 cases in which it seems rheumatroid
» arthritis drugs restored hair.
»
» What is interesting about these 3 cases is that:
»
» 1) growth of hairs was over an area of scalp that he
» previously been devoid of visible hair

»
» 2) and the new density of new hair growth on the
» scalp was equal to that on the areas of his scalp that were not subject to
» balding.

»
» 3) They were male pattern baldness sufferers
»
» this is something that sounds like a complete cure. The ultimate goal we
» are after. And its been done 3 times on humans. Noone else acheived
» anything even margnaly close to this.
»
» First two cases are on benoxaprofen.
»
» Third is recent report of hlh user who reported that he regrew 3cm of slick
» bald frontal hairline loss to full density and teen like coverage while he
» was taking sulfasalazine.
»
» The timeline for these incidents were 5-9 months of continuous oral drug
» intake to see the regrowth. The dosages of sulfasalazine was 3000mg a day.
»
» I already posted 2 related threads where more information can be found:
»
» benoxaprofen:
» http://www.hairsite.com/hair-loss/forum_entry-id-32535-page-0-category-1-order-last_answer.html
»
» sulfasalazine and benoxaprofen:
» http://www.hairsite.com/hair-loss/board_entry-id-84934.html
»
» Bellow here is a summary of my findings so far:
»
» Both benoxaprofen an sulfasalazine have few things in common.
»
» One is for almost sure. The drugs alone wont grow hair. I concluded this
» from the fact that plenty of ppl take the drugs, so if hair growth was
» common side effect, they would have noticed. The ultimate goal of this
» thread would be to find out what is the missing part that together with
» these drugs gave the users the pleasant side effect.
»
» They have similar side effects (photosensitivity for example). Both are
» anti inflamatory drugs used to treat rheumatoic arthritis and similar
» diseases.
»
» Theres also a study that says that misture of iron ions together with
» 5-aminolevulinic-acid 5ala (active component in sulfasalazine) grows hair
» in mice
»
» http://inhumanexperiment.blogspot.com/2008/12/mixture-of-5-aminolevulinic-acid-and.html
»
»
» And patent that shows growth in humans (although its not sure if these were
» male pattern baldness cases at all):
»
» http://www.google.com/patents?hl=cs&lr=&vid=USPATAPP11568322&id=oE2iAAAAEBAJ&oi=fnd&dq=5-aminolevulinic+acid+"male+pattern"&printsec=abstract#v=onepage&q=5-aminolevulinic%20acid%20"male%20pattern"&f=false
»
» The regrowth in the patent is unusualy fast (4-7 weeks).
»
» There is some minor evidence that arthritis has to do with some lack of
» some bone progenitor cells (and we know that hairloss has to do with lack
» of hair follicle progenitor cells as well)
»
» http://scholar.google.com/scholar?q=progenitor+arthritis
»
» Sulfasalazine is also used to reverse fibrosis.
»
» http://www.gastrojournal.org/article/S0016-5085(04)01847-5/abstract?referrer=http://scholar.google.cz/scholar?q=sulfasalazine+fibrosis&hl=cs&btnG=Hledat
»
» We also speculated that it could be sunburn (the photosensitivity damage) +
» the drug that stimulates the new growth.
»
» This is very weak hypothesis. To support it we only have a gefinitib guy
» case which somehow shows regrowth on areas exposed to sun (if he got
» sunburn from back to front). All in all, i consider this to be just
» speculation.
»
» http://www.hairsite.com/hair-loss/forum_entry-id-33436.html
»
» Although it should also be stated that the patent also suggests that
» opposite can be acheived (if too much of 5-ala together with photo
» stimulation is used, follicles can be damaged).
»
» If we were to try topical mixture of 5-ala and iron ions or mixture based
» on the patents, we should probably first test it on areas where possible
» hairloss wont bother us (very back of our neck for example) to find out if
» its safe. Also both users of anti androgens and users who do not use
» antiandrogens at all should try to test this, because atm we dont know if
» that can interfere with the treatment.
»
» Im sick of this disease. Lets try to crack this down.
»
» Everyone who can contribute please do so. Everyone who knows anyone who is
» scientificaly interested or knows any hair loss site user who is especialy
» bright in science of hairloss, please notify them of this thread.

None of these guys tried anything topical right? They did nothing more than take their daily dose of sulfasalazine or benoxaprofen, correct?


#7

where would you go about finding 5-ala and iron ions?


#8

» None of these guys tried anything topical right? They did nothing more
» than take their daily dose of sulfasalazine or benoxaprofen, correct?

Thats correct. If they did anything more, then it hasnt been reported.


#9

» » None of these guys tried anything topical right? They did nothing more
» » than take their daily dose of sulfasalazine or benoxaprofen, correct?
»
» Thats correct. If they did anything more, then it hasnt been reported.

This is worse for the FIN and Minox industry i guess


#10

» where would you go about finding 5-ala and iron ions?

Good question, also can someone summarize that study, the english is hard to follow, does anyone really understand what’s going on there?


#11

Is it safe to say that the reason why the patients on Sulfasalazine & Benoxaprofen regrew hair was due to PGE2 levels being increased. Numerous studies have shown that Sulfasalazine doubles PGE2 levels. Benoxaprofen increases photo sensitivity in patients, sunlight (UVB) and sunburn increases PGE2 levels. There is almost no doubt in my mind that these patients regrew hair by huge increases in PGE2. Anyone who is currently on a PGD2 blocker or PGE2 agonist, can you please try to achieve UVB-induced sunburn, possibly using a tanning bed?. I would be interested in seeing the results. Thanks.


#12

» Is it safe to say that the reason why the patients on Sulfasalazine &
» Benoxaprofen regrew hair was due to PGE2 levels being increased. Numerous
» studies have shown that Sulfasalazine doubles PGE2 levels. Benoxaprofen
» increases photo sensitivity in patients, sunlight (UVB) and sunburn
» increases PGE2 levels. There is almost no doubt in my mind that these
» patients regrew hair by huge increases in PGE2. Anyone who is currently on
» a PGD2 blocker or PGE2 agonist, can you please try to achieve UVB-induced
» sunburn, possibly using a tanning bed?. I would be interested in seeing the
» results. Thanks.

Great insight! Very interesting when you consider the Cotsarelis work on wounding.

I’ll be in the Caribbean for 10 days soon and am on OC. Maybe i’ll come back with a full head of hair :slight_smile:


#13

» » Is it safe to say that the reason why the patients on Sulfasalazine &
» » Benoxaprofen regrew hair was due to PGE2 levels being increased.
» Numerous
» » studies have shown that Sulfasalazine doubles PGE2 levels. Benoxaprofen
» » increases photo sensitivity in patients, sunlight (UVB) and sunburn
» » increases PGE2 levels. There is almost no doubt in my mind that these
» » patients regrew hair by huge increases in PGE2. Anyone who is currently
» on
» » a PGD2 blocker or PGE2 agonist, can you please try to achieve
» UVB-induced
» » sunburn, possibly using a tanning bed?. I would be interested in seeing
» the
» » results. Thanks.
»
» Great insight! Very interesting when you consider the Cotsarelis work on
» wounding.
»
» I’ll be in the Caribbean for 10 days soon and am on OC. Maybe i’ll come
» back with a full head of hair :slight_smile:

And if I remember correctly… the patient with cancer that was treated with gefitinib regrew some hair after a sunburn…


#14

Llight and laser therapy and its effects on hair growth,

http://dermatology.cdlib.org/1802/02_rev/03_11-00182/article.html

Another hypothesis,

UV light may induce hypertrichosis through production of PGE2

Medical Hypotheses
Volume 68, Issue 4, 2007, Pages 917-918
M.R. Namazi
Dermatology Department, Shiraz University of Medical Sciences, Shiraz, Iran

Sunlight has been known to have the tendency to induce hypertrichosis – an effect potentiated by some agents such as psoralen and benoxaprofene [1]. The mechanism underlying this effect has not, however, been explained so far. Below, a mechanism is suggested to account for this interesting phenomenon:

UV irradiation is a potent inducer of cyclooxygenase (COX)2 enzyme and produces high levels of PGE2 in the skin [2]. PGE2 is known to stimulate hair growth. Prostaglandins have been reported to stimulate eyelash growth in patients using them in eye preparations for glaucoma and body and scalp hair growth when used topically in various animal models. Interestingly, it has even been proposed that a large part of minoxidil’s therapeutic efficacy against hair loss could be attributed to its activation of prostaglandin H synthase (PGHS)-1 which produces high levels of PGE2 [3].

How PGE2 induces hair growth? PGE2 is known to increase intracellular cAMP levels [4]. Glucose-6-phosphate dehydrogenase (G6PD) activity is then stimulated by cAMP, which increases during the anagen cycle [5]. It should be noted that the inhibitory effect of dehydrotestosterone and dehydroepiandrosterone on hair growth has been attributed to their inhibitory effects on adenyl cylase and G6PD, respectively [5].

Therefore, given that UV irradiation produces PGE2 as the result of its activation of (COX)2, and that PGE2 stimulates hair growth, it could be reasoned that UV light may produce hypertrichosis through production of PGE2.

References

[1] R.P.R. Dawber, D. de Beker and F. Wojnarowska, Disorders of hair (6th ed.). In: R.H. Champion, J.L. Burton and F.J.G. Ebling, Editors, Rook’s textbook of dermatology vol. 3, Blackwell Scientific Publications, Oxford (1998), p. 2894.

[2] I.F. Orengo, J. Gerguis, R. Philips, A. Guevava, A.T. Lewis and H.S. Black, Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV-induced skin cancer, Arch Dermatol 138 (2002), pp. 751–755. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (55)

[3] R. Wolf, H. Matz, M. Zalish, A. Pollack and E. Orion, Prostaglandin analogs for hair growth: great expectations, Dermatol Online J 9 (2003) (3), p. 7. View Record in Scopus | Cited By in Scopus (6)

[4] M.R. Namazi, The beneficial and detrimental effects of linoleic acid on autoimmune disorders, Autoimmunity 37 (2004) (1), pp. 73–75. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (2)

[5] W.F. Bergfeld, Androgenetic alopecia:next term an autosomal dominant disorder, Am J Med 98 (1995) (Suppl. 1A), pp. 95S–98S.


#15

» Llight and laser therapy and its effects on hair growth,
»
» http://dermatology.cdlib.org/1802/02_rev/03_11-00182/article.html
»
» Another hypothesis,
»
» UV light may induce hypertrichosis through production of PGE2
»
» Medical Hypotheses
» Volume 68, Issue 4, 2007, Pages 917-918
» M.R. Namazi
» Dermatology Department, Shiraz University of Medical Sciences, Shiraz,
» Iran
»
» Sunlight has been known to have the tendency to induce hypertrichosis – an
» effect potentiated by some agents such as psoralen and benoxaprofene [1].
» The mechanism underlying this effect has not, however, been explained so
» far. Below, a mechanism is suggested to account for this interesting
» phenomenon:
»
» UV irradiation is a potent inducer of cyclooxygenase (COX)2 enzyme and
» produces high levels of PGE2 in the skin [2]. PGE2 is known to stimulate
» hair growth. Prostaglandins have been reported to stimulate eyelash growth
» in patients using them in eye preparations for glaucoma and body and scalp
» hair growth when used topically in various animal models. Interestingly, it
» has even been proposed that a large part of minoxidil’s therapeutic
» efficacy against hair loss could be attributed to its activation of
» prostaglandin H synthase (PGHS)-1 which produces high levels of PGE2 [3].
»
» How PGE2 induces hair growth? PGE2 is known to increase intracellular cAMP
» levels [4]. Glucose-6-phosphate dehydrogenase (G6PD) activity is then
» stimulated by cAMP, which increases during the anagen cycle [5]. It should
» be noted that the inhibitory effect of dehydrotestosterone and
» dehydroepiandrosterone on hair growth has been attributed to their
» inhibitory effects on adenyl cylase and G6PD, respectively [5].
»
» Therefore, given that UV irradiation produces PGE2 as the result of its
» activation of (COX)2, and that PGE2 stimulates hair growth, it could be
» reasoned that UV light may produce hypertrichosis through production of
» PGE2.
»
»
» References
»
» [1] R.P.R. Dawber, D. de Beker and F. Wojnarowska, Disorders of hair (6th
» ed.). In: R.H. Champion, J.L. Burton and F.J.G. Ebling, Editors, Rook’s
» textbook of dermatology vol. 3, Blackwell Scientific Publications, Oxford
» (1998), p. 2894.
»
» [2] I.F. Orengo, J. Gerguis, R. Philips, A. Guevava, A.T. Lewis and H.S.
» Black, Celecoxib, a cyclooxygenase 2 inhibitor as a potential
» chemopreventive to UV-induced skin cancer, Arch Dermatol 138 (2002), pp.
» 751–755. Full Text via CrossRef | View Record in Scopus | Cited By in
» Scopus (55)
»
» [3] R. Wolf, H. Matz, M. Zalish, A. Pollack and E. Orion, Prostaglandin
» analogs for hair growth: great expectations, Dermatol Online J 9 (2003)
» (3), p. 7. View Record in Scopus | Cited By in Scopus (6)
»
» [4] M.R. Namazi, The beneficial and detrimental effects of linoleic acid on
» autoimmune disorders, Autoimmunity 37 (2004) (1), pp. 73–75. Full Text via
» CrossRef | View Record in Scopus | Cited By in Scopus (2)
»
» [5] W.F. Bergfeld, Androgenetic alopecia:next term an autosomal dominant
» disorder, Am J Med 98 (1995) (Suppl. 1A), pp. 95S–98S.

Wonder if LLLT accomplishes the same?


#16

I may have some information to add to this, firstly do we know what type of arthritis the 3 lucky guys had that were treated with these drugs?

Gilberts syndrome, apparently protects people from developing rheumatoid arthritis with a 98% confidence interval,

The guy in the UK that started the gilberts syndrome website claims on his sight, that he has noticed a high prevalence of male pattern baldness in people with gilberts syndrome.

He also claims that after taking propecia for a few months the drug dramatically reduced his hyperunconjugated bilirubinemia (high blood bilirubin) which is what gilberts syndrome is, in a nut shell.

I also remember reading that a doctor told a famous singer song writer peter Gabriel I think? That he could make his hair grow back by controlling the rate his red blood cells live for, which from knowledge I know either meant increasing or decreasing blood bilirubin levels. The way they do this is probably heating the blood to induce “heat shock protein 1” which will induce I think heme oxygenase, producing bilirubin as by product which will then competitively inhibit the conjugation of all endogenous & exogenous UGT substrates, which one important one is oestrogen.

Funny that those drugs cause skin sensitivity too don’t you think? Vitamin d connection here and calcium which connects with oestrogen, which connects with bone formation which connects with the need for the medication in the first place, which is arthritis.

The opposite of skin sensitivity to sunlight is a tan and the peptides that produce a tan are known to darken hair colour alfa msh (melanocyte stimulating hormone) melanotan peptides, and msh is also known to repair tooth enamel formation from decay, which is known to require calcium phosphate, and last but not least calcium phosphate binds with bilirubin to make an insoluble complex in the gut. I wonder if people with gilberts syndrome have bad teeth as a result?

oh yeah and wouldnt breaking down red blood cells increase free iron?


#17

Let me start off by saying that EGFR inhibitors have serious side effects and should always be used with extreme caution.

What’s the relationship between Sulfasalazine, benoxprofen, and EGFR inhibitors?

Links showing these drugs increase hair growth in some users,

http://dermatology-s10.cdlib.org/1503/case_reports/egfr/alexandrescu.html

http://community.macmillan.org.uk/cancer_types/bowel-colon-rectum-cancer/f/26/p/51239/520577.aspx

http://www.cancercompass.com/message-board/message/all,42682,0.htm

https://docs.google.com/viewer?a=v&q=cache:qX1GU2NNIu4J:jco.ascopubs.org/content/29/18/e532.full.pdf+cetuximab+facial+hair&hl=en&gl=us&pid=bl&srcid=ADGEESgkAWe9Rrba4ox8o6k_xL73qXRLis8I71YetQvoV9Xw9s8Q9ctEqny3AGCum9ww-YLDcjYOGi1E0YNbnUhCKIzuwrY5rRuMupT-WRwOp6Yel5qGpa3bs6WIJd8Wvg7HB1UwAQB5&sig=AHIEtbQ4U8Kzv3hi90wJ1WGMpdD61u31Pg

These drugs all cause photosensitivity . EGFR is found in the skin and follicles.


#18

» I may have some information to add to this, firstly do we know what type of
» arthritis the 3 lucky guys had that were treated with these drugs?
»
» Gilberts syndrome, apparently protects people from developing rheumatoid
» arthritis with a 98% confidence interval,
»
» The guy in the UK that started the gilberts syndrome website claims on his
» sight, that he has noticed a high prevalence of male pattern baldness in
» people with gilberts syndrome.
»
» He also claims that after taking propecia for a few months the drug
» dramatically reduced his hyperunconjugated bilirubinemia (high blood
» bilirubin) which is what gilberts syndrome is, in a nut shell.
»
» I also remember reading that a doctor told a famous singer song writer
» peter Gabriel I think? That he could make his hair grow back by controlling
» the rate his red blood cells live for, which from knowledge I know either
» meant increasing or decreasing blood bilirubin levels. The way they do this
» is probably heating the blood to induce “heat shock protein 1” which will
» induce I think heme oxygenase, producing bilirubin as by product which will
» then competitively inhibit the conjugation of all endogenous & exogenous
» UGT substrates, which one important one is oestrogen.
»
» Funny that those drugs cause skin sensitivity too don’t you think? Vitamin
» d connection here and calcium which connects with oestrogen, which connects
» with bone formation which connects with the need for the medication in the
» first place, which is arthritis.
»
» The opposite of skin sensitivity to sunlight is a tan and the peptides that
» produce a tan are known to darken hair colour alfa msh (melanocyte
» stimulating hormone) melanotan peptides, and msh is also known to repair
» tooth enamel formation from decay, which is known to require calcium
» phosphate, and last but not least calcium phosphate binds with bilirubin to
» make an insoluble complex in the gut. I wonder if people with gilberts
» syndrome have bad teeth as a result?
»
» oh yeah and wouldnt breaking down red blood cells increase free iron?

You are correct about heme oxagenase. An essential oil, Thuja Orientalis increases heme oxagenase which also has other hair growth properties (I posted on the other hairloss site help)
Turns out that Thuja induces 5-aminolevolic acid synthase, 5-ALA was reported to grow hair in one or two patients. 5-ALA is the main ingredient in sulfasalazine.


#19

Benoxaprofen inhibits 5-lox pathway.

http://books.google.com/books?id=CCsFcFBhzDsC&pg=PT481&lpg=PT481&ots=violS7bgWy&dq=benoxaprofen+inhibits+5lox&output=html_text


#20

I hate to keep bumping this thread but please bear with me. We all know scalp wounding grows new hair according to the studies by Cots and others. All of these drugs increase photosensitivity which means the damage induced by the suns rays must have elevated PGE2 and pro-inflammatory cytokines to very high levels. Can we possibly create a hair growth recipe consisting of a PGD2 blocker, PGE2 agonist, Photosensitivity promoter, and UVA/UVB Lighting. I am a bit concerned that the dosage of pge2 being used by some people isnt high enough or isn’t properly being absorbed topically.

In the laboratory, anagen can be induced under controlled conditions by taking advantage of the fact that hair growth is initiated by trauma/wounding Trauma/wounding may mean hair plucking, vigorous shaving, or chemical exposure (e.g., caustic materials, depilatory agents). In this respect, we do not know what “trauma/wounding” actually means, although we do know that clipping the hair shaft without injury to the skin surface and follicle epithelium does not initiate growth. That trauma may have effects (cell necrosis, inflammation) besides the induction of growth has been documented . We assume trauma/wounding causes the release of proinflammatory cytokines that directly initiate anagen. Although we doubt that this form of initiation accurately reflects the spontaneous event, we assume that at least some aspects of the pathway(s) activated are common to the two situations.

It has been found that the traumatic stimulus has a certain threshold below which synchronized growth will not occur. Chase and Eaton found that at least 1,000 hair shafts have to be plucked to initiate hair growth; plucking a single hair in the mouse does not initiate anagen activity in that follicle . This observation suggests that the pathway requires a quantifiably minimal threshold stimulus. It is also notable that the traumatic signal does not appear to spread beyond the area of wounding.