Relationship between the plasma testosterone level and pain reaction times in male rats
Male prepubertal (about 4 weeks old) Wistar rats were used to estimate the pain reaction times using the tail-flick and hot-plate models; the testosterone concentration in all the animals before the tests in the blood plasma was measured. The same sets of animals were kept for the next 4 weeks under...
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| Дата: | 2009 |
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Інститут фізіології ім. О.О. Богомольця НАН України
2009
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| Цитувати: | Relationship between the plasma testosterone level and pain reaction times in male rats / O.A. Oyekunle, G. Fibironke, S.F. Ige, U.S. Udoh, A.K. Okojie // Нейрофизиология. — 2009. — Т. 41, № 3. — С. 231-234. — Бібліогр.: 22 назв. — англ. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1860243726530510848 |
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| author | Oyekunle, O.A. Fibironke, G. Ige, S.F. Udoh, U.S. Okojie, A.K. |
| author_facet | Oyekunle, O.A. Fibironke, G. Ige, S.F. Udoh, U.S. Okojie, A.K. |
| citation_txt | Relationship between the plasma testosterone level and pain reaction times in male rats / O.A. Oyekunle, G. Fibironke, S.F. Ige, U.S. Udoh, A.K. Okojie // Нейрофизиология. — 2009. — Т. 41, № 3. — С. 231-234. — Бібліогр.: 22 назв. — англ. |
| collection | DSpace DC |
| container_title | Нейрофизиология |
| description | Male prepubertal (about 4 weeks old) Wistar rats were used to estimate the pain reaction times using the tail-flick and hot-plate models; the testosterone concentration in all the animals before the tests in the blood plasma was measured. The same sets of animals were kept for the next 4 weeks under standard conditions; the experiment was repeated, and pain reaction times were also evaluated in the 8-week-old rats with blood samples collected to determine the plasma testosterone level. The results showed significant (P < 0.01) increases in the pain reaction times in both pain models in pubertal animals observed in a parallel manner with a corresponding significant (P < 0.01) increase in the plasma testosterone level. Therefore, age and sex are important factors in the choice of animals in pain experiments.
У щурів-самців препубертатного віку (чотири тижні) вимірювали латентні періоди больових реакцій в умовах тестів «відсмикування хвоста» та «гарячої пластинки»; у всіх тварин перед тестами вимірювалася концентрація тестостерону в плазмі крові. Ці ж самі групи тварин утримувалися протягом чотирьох тижнів у стандартних умовах, після чого експеримент повторювали на восьмитижневих щурах (вимірювали час больових реакцій та рівень тестостерону). Для тварин, що досягли віку статевої зрілості, було характерне істотне (P < 0.01) збільшення латентних періодів больових реакцій в обох використаних моделях, що відбувалося паралельно з відповідним вірогідним (P < 0.01) збільшенням рівня тестостерону в плазмі. Отже, вік і стать є найважливішими факторами при відборі тварин для проведення експериментів з больовою стимуляцією.
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НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2009.—T. 41, № 3 231
UDC 577.17+612.884
O. A. OYEKUNLE1, G. FIBIRONKE2, S. F. IGE1, U. S. UDOH1, AND A. K. OKOJIE1
RELATIONSHIP BETWEEN THE PLASMA TESTOSTERONE LEVEL
AND PAIN REACTION TIMES IN MALE RATS
Received 10.01.09
Male prepubertal (about 4 weeks old) Wistar rats were used to estimate the pain reaction times
using the tail-flick and hot-plate models; the testosterone concentration in all the animals
before the tests in the blood plasma was measured. The same sets of animals were kept for
the next 4 weeks under standard conditions; the experiment was repeated, and pain reaction
times were also evaluated in the 8-week-old rats with blood samples collected to determine
the plasma testosterone level. The results showed significant (P < 0.01) increases in the pain
reaction times in both pain models in pubertal animals observed in a parallel manner with a
corresponding significant (P < 0.01) increase in the plasma testosterone level. Therefore, age
and sex are important factors in the choice of animals in pain experiments.
Keywords: tail flick, hot plate, testosterone, pain reaction time.
1 Faculty of Basic Medical Sciences, Ladoke Akintola University of
Technology, Ogbomoso, Nigeria.
2 Faculty of Basic Medical Sciences, University of Ibadan, Ibadan. Nigeria.
Correspondence should be addressed to A. K. Okojie
(e-mail: pintos4live@yahoo.com).
INTRODUCTION
Expanding literature indicates that gender is an
important factor influencing the experience of pain.
Clinical and laboratory observations [1-4] led to a
general conclusion that females and males noticeably
differ from each other in their perception and experience
of pain; females typically showed a greater sensitivity
to and less tolerance for experimentally induced
noxious stimulation than males did. Experimental
and clinical data demonstrated that gonadal hormones
significantly affect pain-induced responses [4-6].
There could be a number of reasons for the differences
recorded in the pain reactivity between males and
females, from dissimilar genes to hormonal and
cultural (in humans) influences. Gonadal hormones
possess the respective receptors present in many brain
areas, including some involved in pain transmission
and modulation. Testosterone as a major gonadal
hormone in mature males has been known to play a
protective role manifested, e.g., in adjuvant-induced
arthritis [7] and in chronic pain stimulation [8].
Male rats with a physiological level of testosterone
recovered better than gonadectomized males with very
low testosterone levels.
Exogenous testosterone (testosterone propionate)
injections in male and female rats were found to
modulate behavioral responses differently in both
sexes when evaluated with a chronic model of pain.
This intervention was reported to influence all the
organization of behavior, decreasing the behavior
entropy, which is connected with a precipitation of
the process of inhibition of the exploratory activity
and emotional reactivity, simultaneously changing the
dynamics of the behavioral entropy [9].
In this study, we examined the relationship between
the testosterone concentration in the blood plasma and
pain reaction times using two pain behavioral tests
(hot plate and tail flick) in immature and pubertal
male rats.
METHODS
Two groups, including 8 prepubertal male rats (4 weeks
old) each, were used in the study. Animals were housed
under standard vivarium conditions at about 25 ±
± 1°C with an alternating 12 h/12 h light-dark cycle.
Food and water were made available ad libitum; all
experimental manipulations were carried out between
9.00 and 12.00. The same groups of the animals were
examined 4 weeks later, i.e., when the animals reached
the pubertal age.
Hot Plate. Rats were placed on a hot plate maintained
at 55.5 ± 0.5°C according to the described procedure
НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2009.—T. 41, № 3232
[10]. The reaction time was measured from the moment
of placing until either jumping off the plate or licking
of the hind paw(s). The cut-off imposed for heating
was 60 sec, to avoid tissue damage [11]. Each rat was
tested twice, with a 20-min-long interval, and the
reaction times were averaged.
Tail Flick. The tail-flick reaction was evoked by a
source of radiant heat focused on the dorsal surface
of the tail according to the procedure described by
D’Amour and Smith [12] and modified by Dewey et
al. [13]. Each rat was tested twice (with a sufficient
interval), and the reaction times were also averaged
to obtain a baseline. The cut-off time of 10 sec for
heating was imposed to prevent tissue damage.
Measuring of the Testosterone Level. Blood samples were
collected from the middle vein of the ear and centrifuged
at 3000 rev. min for 3 to 5 min. The testosterone level in
the blood plasma was measured using standard enzyme-
linked immunosorbent assay (Microwell Method, Dialab,
Austria) with parallel measurements in the respective
calibrators attached to the kit.
RESULTS
In the group of 4-week-old rats subjected to the hot-
plate tests, the level of testosterone in the blood plasma
was 9.50 ± 0.65 nM, on average. On the 8th week, this
index increased more than twofold and reached 19.70
± 1.40 nM (P < 0.01). The mean delay in the reaction
to noxious thermostimulation in 4-week-old animals
subjected to the above test was 37.73 ± 1.80 sec. In
rats reaching the age of pubertation (8 weeks), the
mean reaction time in this test was 186.90 ± 8.90 sec,
i.e., it was nearly five times longer than in the first
measurement (P < 0.01).
The observation made in the tail-flick group
were quite comparable. The results of testosterone
measurements were qualitatively the same but
somewhat differed from the quantitative aspect. In
the tail-flick group, the mean testosterone level in
4-week-old animals was 11.20 ± 0.56 nM, i.e., it was
nearly the same as in the hot-plate group. At 8 weeks,
this index increased to 39.10 ± 1.90 nM, i.e. an increase
was noticeably greater than in the former group (more
than threefold; P < 0.01). Yet, such a difference was
not unexpected because there was no pre-experimental
standardization of the animals according to their
secretion capabilities, and individual variability
influencing the intergroup mean was quite natural. In
the tail-flick test, the average reaction time of 4-week-
old animals was 37.75 ± 0.65 sec. In 8-week rats, this
time increased twofold (74.62 ± 1.25 sec; P < 0.01).
DISCUSSION
Experimental and clinical data have implicated the presence
of a sex-hormone factor in most parameters affected
by painful stimulation [14]. There has been increasing
evidence that the brain not only respond to hormones
produced by the reproductive system, but that the levels
of these hormones, the so-called “female hormone”
estrogen and progestin and the “male” androgen, such as
testosterone, play important roles in the perception of pain
and its modulation [15]. Our investigation focuses on the
differences in the perception of pain (or pain reaction time)
in immature and (relatively) mature stages of ontogenesis
of the same male rats. The initial rather low (nonetheless,
quite noticeable) testosterone concentrations observed in
the blood plasma of prepubertal rats in our study are related
to testosterone produced within this period mostly by some
other sources than the testes, such as the adrenals [16].
The matured male rats well tolerated the stimuli
in both experimental models of evaluation thereby
increasing the delays of pain behavioral reactions
recorded from them [17]. The presence of testosterone
in a much more significant amount should be
considered one of the main crucial factors responsible
for this inhibition (or tolerance) in matured males. The
observation that testosterone has a protective role is
supported by earlier demonstrations that this hormone
can reduce the intensity of nociception by inhibiting
its inflammation-related component [18]. Our results
also agree with the results obtained by Aloisi et al. [19]
and Hau et al. [20] who showed a protective role for
testosterone in their various studies. In our experiments,
we observed a quite obvious and close relationship
between the plasma testosterone concentration and the
pain reaction times, which is in agreement with earlier
studies [20], except that our data were collected in same
animals at different stages of sexual development. Also
testosterone seems to be responsible for a habituation
capacity in intact males during repetitive nociceptive
stimulations, which is lost in castrated males [8]. This
is also in agreement with our results.
Of course, the role of other factors influencing
changes in the pain sensitivity in maturating animals
should not be underestimated. First of all, this is an
increase in the mass of the animals and the respective
increase in the thickness of the skin on the pads and tail
(accompanied by the improvement of thermoisolation
O. A. OYEKUNLE, G. FIBIRONKE, S. F. IGE, at al.
НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2009.—T. 41, № 3 233
properties). It should, however be taken into account
that growth of a maturating animal and changes
in the properties of its skin (to say nothing on the
peculiarities of the composition and density of somatic
receptors of different modalities in these tissues) are
also interlinked hormone-dependent phenomena.
Different environmental factors and seasonal changes
also influence, to a certain extent, the parameters of
pain reactions (both experimental and observed in
clinics). Nonetheless, the state of the system of the
mail sex hormone looks as one of the most important
factors influencing the brain systems of nociception
and antinociception. As is known, there is abundant
distribution of testosterone receptors in the brain.
The roles of endogenous mediators of nociception
in relation to the testosterone concentration and
activation of testosterone receptors may be an urgent
circle of questions for further studies.
Furthermore, it is important to point out that the role
of the hormonal background (in our case, testosterone)
in pain reception has too often been neglected. It was
reported that testosterone can provide the reduction of
some clinical pain in both men [21, 22] and women [5].
Finally, our observations highlight the importance of
taking into account the hormonal status of experimental
animals when evaluating pain perception and/or pain
inhibition. Therefore, the choice of experimental
animals for pain experiments should be based on their
age and sex rather than on their weight. It should
be recognized that just the latter aspect has become
a norm over the years, while the role played by sex
hormones in pain perception was underestimated.
Therefore, in some cases using immature animals in
such experimental studies will be more appropriate.
O. А. Ойєкунле1, Г. Фібіронке2, С. Ф. Іге1, Ю. С. Уго1,
А. К. Окойє1
ЗАЛЕЖНІСТЬ МІЖ РІВНЕМ ТЕСТОСТЕРОНУ В ПЛАЗМІ
КРОВІ ТА ЛАТЕНТНИМИ ПЕРІОДАМИ БОЛЬОВИХ
РЕАКЦИЙ У САМЦІВ ЩУРІВ
1 Факультет медичних наук, Технологічний університет
Ладоке Акінтола, Огбомозо (Нігерія).
2 Факультет медичних наук, Ібаданський університет,
Ібадан (Нігерія).
Р е з ю м е
У щурів-самців препубертатного віку (чотири тижні)
вимірювали латентні періоди больових реакцій в умовах
тестів «відсмикування хвоста» та «гарячої пластинки»;
у всіх тварин перед тестами вимірювалася концентрація
тестостерону в плазмі крові. Ці ж самі групи тварин
утримувалися протягом чотирьох тижнів у стандартних
умовах, після чого експеримент повторювали на
восьмитижневих щурах (вимірювали час больових реакцій
та рівень тестостерону). Для тварин, що досягли віку статевої
зрілості, було характерне істотне (P < 0.01) збільшення
латентних періодів больових реакцій в обох використаних
моделях, що відбувалося паралельно з відповідним
вірогідним (P < 0.01) збільшенням рівня тестостерону в
плазмі. Отже, вік і стать є найважливішими факторами при
відборі тварин для проведення експериментів з больовою
стимуляцією.
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RELATIONSHIP BETWEEN THE PLASMA TESTOSTERONE LEVEL AND PAIN REACTION
НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2009.—T. 41, № 3234
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O. A. Oyekunle, G. Fibironke, S. F. Ige, at al.
|
| id | nasplib_isofts_kiev_ua-123456789-68294 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 0028-2561 |
| language | English |
| last_indexed | 2025-12-07T18:33:19Z |
| publishDate | 2009 |
| publisher | Інститут фізіології ім. О.О. Богомольця НАН України |
| record_format | dspace |
| spelling | Oyekunle, O.A. Fibironke, G. Ige, S.F. Udoh, U.S. Okojie, A.K. 2014-09-20T15:06:27Z 2014-09-20T15:06:27Z 2009 Relationship between the plasma testosterone level and pain reaction times in male rats / O.A. Oyekunle, G. Fibironke, S.F. Ige, U.S. Udoh, A.K. Okojie // Нейрофизиология. — 2009. — Т. 41, № 3. — С. 231-234. — Бібліогр.: 22 назв. — англ. 0028-2561 https://nasplib.isofts.kiev.ua/handle/123456789/68294 577.17+612.884 Male prepubertal (about 4 weeks old) Wistar rats were used to estimate the pain reaction times using the tail-flick and hot-plate models; the testosterone concentration in all the animals before the tests in the blood plasma was measured. The same sets of animals were kept for the next 4 weeks under standard conditions; the experiment was repeated, and pain reaction times were also evaluated in the 8-week-old rats with blood samples collected to determine the plasma testosterone level. The results showed significant (P < 0.01) increases in the pain reaction times in both pain models in pubertal animals observed in a parallel manner with a corresponding significant (P < 0.01) increase in the plasma testosterone level. Therefore, age and sex are important factors in the choice of animals in pain experiments. У щурів-самців препубертатного віку (чотири тижні) вимірювали латентні періоди больових реакцій в умовах тестів «відсмикування хвоста» та «гарячої пластинки»; у всіх тварин перед тестами вимірювалася концентрація тестостерону в плазмі крові. Ці ж самі групи тварин утримувалися протягом чотирьох тижнів у стандартних умовах, після чого експеримент повторювали на восьмитижневих щурах (вимірювали час больових реакцій та рівень тестостерону). Для тварин, що досягли віку статевої зрілості, було характерне істотне (P < 0.01) збільшення латентних періодів больових реакцій в обох використаних моделях, що відбувалося паралельно з відповідним вірогідним (P < 0.01) збільшенням рівня тестостерону в плазмі. Отже, вік і стать є найважливішими факторами при відборі тварин для проведення експериментів з больовою стимуляцією. en Інститут фізіології ім. О.О. Богомольця НАН України Нейрофизиология Relationship between the plasma testosterone level and pain reaction times in male rats Залежність між рівнем тестостерону в плазмі крові та латентними періодами больових реакций у самців щурів Article published earlier |
| spellingShingle | Relationship between the plasma testosterone level and pain reaction times in male rats Oyekunle, O.A. Fibironke, G. Ige, S.F. Udoh, U.S. Okojie, A.K. |
| title | Relationship between the plasma testosterone level and pain reaction times in male rats |
| title_alt | Залежність між рівнем тестостерону в плазмі крові та латентними періодами больових реакций у самців щурів |
| title_full | Relationship between the plasma testosterone level and pain reaction times in male rats |
| title_fullStr | Relationship between the plasma testosterone level and pain reaction times in male rats |
| title_full_unstemmed | Relationship between the plasma testosterone level and pain reaction times in male rats |
| title_short | Relationship between the plasma testosterone level and pain reaction times in male rats |
| title_sort | relationship between the plasma testosterone level and pain reaction times in male rats |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/68294 |
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