and diseases of sense organs)
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caused by stimulation of a nociceptor => Ad
fibers
and C fibers => contralateral spinothalamic tract
=> posterior nucleus of thalamus => primary
somatosensory area
leads to an increase in levels of the natural painkillers enkephalins,
and such tolerance effects may help men to maintain their stamina in fights,
when testosterone levels are high. Testosterone implants to male sparrows
allowed the birds to tolerate discomfort caused by dangling one of their
legs in a beaker of water at 52°C for longer periods. A drug that blocks
the effect of testosterone causes the birds became more than twice as sensitive
to water at 48 ºC, a temperature at which they normally showed little
discomfortref.
There could be a case for administering replacement testosterone to men
with chronic pain. These men often take drugs that lower normal testosterone
levels, interfering with the natural alleviation of their suffering.
and anti-androgens as treatment to become women, 30% reported developing
pains, primarily chronic headaches, during their treatment. In another
study of women taking testosterone to become men, > 50% found their aches
and pains improved. They seemed to feel better generally. The results back
up previous research on sex differences in pain. Although no one knows
exactly how sex hormones affect pain tolerance, researchers think testosterone
dulls pain by muting the excitatory pain pathways in the central nervous
system, while oestrogen heightens pain by blocking the inhibitory mechanisms
that damp pain sensing. The evidence for this is piling up. But the story
about oestrogen is more confusing than it first seemed. On the one hand,
pain typically arises during the menstrual cycle when oestrogen is at its
lowest ebb, as during menstruation. On the other, girls report more pain
than boys from the onset of puberty when oestrogen starts to surge. It
seems to be sudden changes in hormone levels that are the problem, rather
than the levels themselves. It is the withdrawal or fluctuation of
oestradiol that is associated with pain. To check this theory, LeResche
is starting to study women who choose to take the contraceptive pill all
the way through their cycle, so that they never menstruate. LeResche will
investigate whether keeping their oestrogen levels up affects their experience
of pain. Clinicians should measure levels of sex hormones in patients.
An imbalance could be exacerbating their problems. And hormone replacement
therapy could be used in some chronic-pain patients : one trial has been
started that bolsters testosterone in male patients with low levels of
the hormone. This idea could also be applied to women, although she adds
that giving testosterone to women is more complicated than giving it to
men.
,
characterized by numerous membrane-bound granules with dense cores, some
desmosomes, cytoplasmic microfilaments, intranuclear filaments bundled
in parallel to form rodlets, and spikelike processes that interdigitate
with keratinocytes. They are believed to act as touch receptors by association
with meniscus tactus / tactile disk or meniscus (one of the small,
cup-shaped, tactile nerve endings within the skin; many of them are formed
by branches of a single nerve fiber, and each one is in contact with a
single, modified epithelial cell (Merkel cell); they are found in the deep
epidermis, in hair follicles, and in the hard palate, and function as touch
receptors);
however, the mechanical sensations of touch and hearing remain without
a clear understanding of their molecular basis. Recently, the relevant
force-transducing molecules—the mechanosensitive ion channels—have been
identified. Such channel proteins purified from bacteria sense forces from
the lipid bilayer in the absence of other proteins. Recent evidence has
shown that lipids are also intimately involved in opening and closing the
mechanosensitive channels of fungal, plant and animal speciesref.
,
physiology
of tongue,
and diseases of tongue)
,
physiology
of nose,
and diseases
of nose)ref,
the G protein through which odorant receptors signalref,
suggesting that they might express another class of chemosensory receptor.
In addition, small peptides that bind major histocompatibility complex
(MHC) proteins can stimulate some OSNsref,
suggesting that those OSNs might express a class of receptor that detects
peptides rather than small volatile odorants. Finally, although many pheromones
are detected in the vomeronasal organ—an olfactory structure with receptors
that differ from odorant receptorsref1,
ref2—responses
to some mouse pheromones involve the olfactory epitheliumref1,
ref2,
ref3,
raising the possibility that the olfactory epithelium also contains a dedicated
class of pheromone receptors. Certain chemicals in mouse urine can alter
the social or sexual behaviour of other mice. These chemicals work partly
by binding to receptors in a particular structure in the mouse nose, known
as the vomeronasal organ. In humans, however, this organ is thought to
be defunct and the role of pheromones is hotly debated. Finding such receptors
in the lining of the nose, rather the vomeronasal organ, is a more direct
parallel with humansref.
A second family of receptors in the mouse olfactory epithelium was discovered
in 2006. Like odorant receptors, individual mouse trace
amine-associated receptors (TAARs)
are expressed in unique subsets of neurons dispersed in the epithelium.
It is highly unlikely that TAARs are coexpressed with odorant receptors.
In mutant mice that express the odorant receptor MOR28 (Olfr1507) in 50–90%
of OSNsref,
only 0.8% (2 in 250), rather than 50–90%, of neurons that hybridized to
Taar6 or Taar7f probes were co-labelled by a MOR28 probe. It is difficult
to completely exclude coexpression of odorant receptors and TAARs in non-transgenic
olfactory epithelium, because each odorant receptor gene is typically expressed
in only 1 in 1,000 OSNs, or 1 in 250 in the odorant receptor's expression
zoneref1,
ref2.
Notably, at least three murine TAARs detect compounds found in mouse urine,
an important source of social cuesref1,
ref2.
One detects a chemical (b-phenylethylamine)
that is elevated in urine in response to stress, whereas two others detect
chemicals (isoamylamine and trimethylamine) that are elevated in male versus
female mouse urine. Moreover, one of these compounds (isoamylamine) is
reported to act as a male-derived pheromone that accelerates puberty onset
in female miceref.
In addition, the mouse TAAR that recognizes trimethylamine is activated
by extremely dilute mouse urine from sexually mature males, but not females
or prepubescent males. Together, these findings suggest that at least some
murine TAARs detect social cues that may elicit innate behaviours or physiological
responses. This idea is consistent with observations that the olfactory
epithelium is involved in some pheromone responsesref1,
ref2,
ref3,
ref4,
and that certain pheromone responses may involve dual signals from the
olfactory epithelium and vomeronasal organref.
In this regard, it is interesting that one amine reported to accelerate
puberty (isoamylamine) is detected by a TAAR whereas another (isobutylamine)
is detected by receptors in the vomeronasal organref.
Future studies should provide information on the ligands of additional
TAAR family members and illuminate the functional roles played by individual
TAARs. Researchers have not yet carried out a key test to show that activating
or eliminating the receptors alters a mouse's behaviour. But they might
be pheromone receptors. So far, most evidence for human pheromones has
come from behavioural research. Women's menstrual cycles changed in length
after they sniffed the sweat on pads previously worn in the armpits of
another womanref.
Newborn babies move towards a pad carrying the smell of their mother's
breast rather than a clean padref.
Human behaviour is influenced by so many conscious and unconscious factors
that it's hard to measure the subtle changes in behaviour caused by a putative
pheromone. Work on human pheromones seems always to capture both public
interest and scientific scepticism. If the receptors discovered in mice
are indeed pheromone receptors, this could allow researchers to ask concrete
questions about human pheromones. Scientists could, for instance, study
people with mutant versions of the receptors to see if they behave differently
when exposed to candidate pheromones. he latest study makes it harder for
the sceptics. Hopefully, this will catalyse a lot of research by high-powered
scientists. Neuroscientists already know that genes in neurons in the lining
of the nose make > 1,000 different olfactory receptors for identifying
chemical odours. The discovery of this gene family won Buck and Richard
Axel the 2004 Nobel Prize in Physiology or Medicine. To look for other
classes of receptor, Liberles and Buck isolated neurons from mouse noses
and searched for genes that were active only in those cells and were similar
to olfactory receptors. There are 6 genes that code for TAARs in humans.
The researchers next searched through a set of other chemicals to find
those that activated the TAAR receptors. 3 of the chemicals they found
are present in mouse urine, which is known to affect the animals' social
behaviour. One in particular earns the label of a pheromone because it
is produced in the urine of male mice and accelerates the onset of puberty
in females. There may be other as yet undiscovered sensory receptors involved
in detecting mammalian pheromones, perhaps including human ones. A paper
in 2000 showed that a gene for one mouse pheromone receptor in the vomeronasal
organ is also active in the human noseref.
There might be other unidentified ones out there. Liberles and Buck are
now testing whether there are molecules in human urine, sweat and vaginal
fluid that can trigger the receptors and that mig ht be human pheromones.
They also want to examine whether the neurons manufacturing the newfound
receptors are wired up in the brain in a different way from regular, smell-detecting
neurons. If so, they might connect to centres that control our behaviour
or emotions
and geometric optics)
are located
and suppression of this endogenous VEGF-A trap by neutralizing antibodies,
RNA interference or Cre-lox-mediated gene disruption abolishes corneal
avascularity in mice. The spontaneously vascularized corneas of corn1 and
Pax6+/- mice and Pax6+/- patients with aniridia are
deficient in sflt-1, and recombinant sflt-1 administration restores corneal
avascularity in corn1 and Pax6+/- mice. Manatees, the only known
creatures uniformly to have vascularized corneas, do not express sflt-1,
whereas the avascular corneas of dugongs, also members of the order Sirenia,
elephants, the closest extant terrestrial phylogenetic relatives of manatees,
and other marine mammals (dolphins and whales) contain sflt-1, indicating
that it has a crucial, evolutionarily conserved role. The recognition that
sflt-1 is essential for preserving the avascular ambit of the cornea can
rationally guide its use as a platform for angiogenic modulators, supports
its use in treating neovascular diseases, and might provide insight into
the immunological privilege of the cornearef
)
: as all sensitive ways, even optic ways is completely crossed. Refractive
media of the eye allow crossing on temporal retinas (that then will have
direct ways) but not on nasal retinas (that then will cross in optic chiasm).
)
