Biology Reference
In-Depth Information
contributes the greatest morbidity and mortality and severely
impairs the quality of life, (
3, 4
). Early disorders of nerve function
include slowing in nerve conduction velocity (NCV) followed by
axonal degeneration, paranodal demyelination, and loss of myeli-
nated fibers (
5
). DPN are painful in more than 15% of patients, a
substantial proportion of who complain of chronic pain and poor
response to conventional analgesics (
6, 7
). Patients often develop
a compromised ability to perceive tactile sensation, exaggerated
sensitivity to nociceptive stimuli (hyperalgesia or hypoalgesia) or
may perceive normal stimuli as painful (allodynia) (
8-11
).
Small-diameter nerve fibers innervating the skin subserve thermal
sensation and nociception. Skin nerve fibers firing can be triggered
by epidermal cells which may have a role in the pathogenesis of
neuropathic pain (
12
). Small-diameter nerve fibers can be affected
early in peripheral neuropathies, although their injury may not be
detectable by routine neurophysiologic tests (
13
). On the contrary,
skin biopsy has proved to be a reliable tool to examine unmyeli-
nated nerve fibers, as assessed by the quantification of intra-epidermal
nerve fiber (IENF) density and to estimate their degeneration over
time in human neuropathies (
14
). IENFs are unmyelinated axons
with exclusively somatic function, as demonstrated by their degen-
eration after axotomy or gangliotomy and their sparing after rhizo-
tomy or sympathectomy (
15
). Their density can be quantified in
experimental models. Studies have focused on cutaneous innerva-
tion in mouse, but data are scanty on control and disease bearing
rats (
16-18
).
1.2 Small-Fiber
Neuropathy
1.3 Streptozotocin-
Diabetic Rat Model
The chemically induced diabetes such as the STZ model, however,
has several advantages (
19
). It shares a number of features with
human diabetic neuropathy at the functional and biochemical levels
(
20
). Decreased NCV, together with reductions in Na
+
, K
+
-ATPase
activity, is the hallmark of diabetic neuropathy, but these rats pres-
ent various types of early neurological dysfunction (
21
), including
altered pain sensation suggesting early involvement of small noci-
ceptive sensory neurons (
14, 22
).
EPO is a cytokine originally used for its effect on erythropoiesis,
since it supports the survival, proliferation and differentiation of
erythroid progenitor cells. However, in the past few years it has
become clear that EPO is a multifunctional trophic factor, with
potent neurotrophic activity on a variety of neural cells in the central
and peripheral nervous systems (
23-25
). EPO confers protection by
preventing the development of or treating peripheral neuropathies
associated with HIV (
26
), cisplatin (
27, 28
), and taxane (
29
).
EPO acts by binding with its receptors (EPOR), which belong
to the cytokine receptor type I superfamily (
30, 31
). EPO and
EPOR are expressed in cerebral and spinal cord neurons, dorsal root
1.4 Erythropoietin
and Neuroprotection
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