Biology Reference
In-Depth Information
symptoms of neuropathic pain. Examples of such conditions
include diffuse limb pain, back pain, and complex regional pain
syndrome ( 8, 9 ).
Studies using a model of localized nerve inflammation, the
neuritis model, suggest that in patients where there is no clinical
evidence of a nerve injury, painful symptoms may in part be gener-
ated from inflamed peripheral nerves ( 10-13 ). In the neuritis
model, a small strip of absorbable sponge (i.e., Gelfoam) saturated
in an immune-stimulant such as complete Freund's adjuvant (killed
bacterial cell wall), is loosely wrapped around the sciatic nerve.
Within hours following induction, a robust local inflammatory
response occurs in the epineurium ( 11, 14 ). Immune cells, which
include activated macrophages, neutrophils, T lymphocytes, and
granulocytes, accumulate outside of the perineurium ( 10, 11,
13, 14 ). The numbers of these cells peak during the first month
following neuritis and persist for at least three months without
entering the endoneurium ( 14 ). The neuritis model contrasts from
inflammatory pain models that are induced by subcutaneous injec-
tion of immune stimulants into the hind paw (e.g., ( 15 )). Whereas
the neuritis model results in a localized mid-axonal inflammatory
lesion, injection of immune stimulants causes chronic inflammation
and observable edema of the hind paw that predominantly affects
the peripheral terminals of primary sensory neurons. The neuritis
model is therefore more likely to resemble the pathology in those
patients with neuropathic pain who do not show signs of apparent
tissue injury.
The most notable histological feature of the neuritis model is
the lack of axonal degeneration and demyelination compared to
other pain models ( 10, 12, 13 ). Despite this lack of gross nerve
pathology, animals develop signs of mechanical and cold allodynia
as well as heat and mechanical hyperalgesia ( 10, 13, 16 ). These
behavioral changes occur early. Mechanical allodynia for example
develops from 3 h and peaks on days 3-4 following surgery. Such
behavioral changes show signs of recovery by 7 days.
Electrophysiological studies on the neuritis model have shown
that uninjured primary sensory neurons exhibit signs of hyperex-
citability. Intact unmyelinated C- as well as myelinated A
-
nociceptive axons develop ongoing activity, which peaks within a
week of neuritis induction ( 10, 12, 17-19 ). Ongoing activity in
nociceptor neurons may correspond to the symptoms of spontane-
ous pain that are often reported by patients. Ongoing activity is
also considered to play a role in the development of central neuro-
pathic symptoms such as allodynia ( 20-22 ).
The immune mechanisms that underlie pain behavior and
ongoing activity in the neuritis model are only starting to be
explored. The immune cells that congregate at the neuritis site
δ
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