FWD:RSD World News-Neuropathic Pain

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From: byrd45 (Original Message) Sent: 3/27/2007 5:05 PM
UroToday.com- Simon Beggs and Michael Salter of the University of
Toronto Centre for the Study of Pain have written an interesting
research overview that will help to bring BPS/IC clinicians and
researchers "up to speed" on this fascinating topic that certainly
impacts many patients with this syndrome. In it, they outline the
pathophysiological mechanisms known to underlie neuropathic pain,
outline the experimental models that are used for these investigations,
and give an overview of the changes that occur within the peripheral and
central nervous systems following nerve injury.

The International Association for the Study of Pain (IASP) defines
neuropathic pain states as disorders that are characterized by lesions
or dysfunction of the neural system(s) that under normal conditions
transmit noxious information to the central nervous system. Peripheral
neuropathic pain is a consequence of nerve injury applied to a syndrome
of varying pathologies. What unifies these pathologies is that the pain
derives from an initial injury, lesion, damage, or metabolic disruption
to a primary sensory neuron. The abnormal nature of neuropathic pain
means that the pain is often removed from any area of tissue damage or
injury, and the degree of pain may not correlate with the apparent
extent of peripheral tissue damage.

Evoked pain from nerve damage can be 1) allodynic: pain due to a
stimulus that does not normally provoke pain or 2) hyperalgesic: an
increased response to a stimulus that is normally painful. The reader
can appreciate that BPS/IC would have elements of both of these
problems, presenting as an exaggeration of the normal desire to void
that can be allodynic as the bladder starts to fill and hyperalgesic at
filling reaches the point where even unaffected individuals would look
for a bathroom.

Neuropathic pain engenders a wide range of CNS disturbances, including
sleep dysfunction, depression and anxiety. The authors point out that
neuropathic pain is not a passive symptom, but a de facto disorder that
should be considered a disease entity in its own right. Neuropathic pain
can be peripheral or central dependent upon the location of the lesion
or source of the initiating lesion.

Sensory nerve fibers are not simple conduits, but rather the axon is a
complex, specialized biological structure, maintaining electrical and
biochemical communication between peripheral target tissues, the cell
body housed in the dorsal root ganglion and the central terminals within
the spinal cord. It is not clear whether normal primary afferent
activity, amplified by pathological central mechanisms, or abnormal
primary afferent activity, is the principal initiator of ongoing
neuropathic pain. Both mechanisms may have a role in neuropathic pain
behaviors.

The authors discuss central sensitization, a well-known form of
plasticity in the dorsal horn which is a state of heightened sensitivity
of dorsal horn neurons resulting in reduced thresholds of activation and
an increased responsiveness to synaptic input. In effect, it serves to
increase the gain of the dorsal horn nociceptive processing system. It
requires ongoing afferent activity in Aδ and C fibers as a result of
a noxious stimulus. These changes outlast by minutes or hours the
initiating peripheral afferent barrage that triggered the central
response from "wind-up", which is also an activity-dependent enhancement
of nociceptive responsiveness but that reverses in less than seconds
after the end of stimulation. Central sensitization and wind-up differ
not only in time-course but also mechanistically.

The authors of this fascinating review conclude that research suggests
that the key molecular mechanisms are not restricted to neurons but also
involve glial cells and glial-neuronal signaling in the spinal cord,
with the preponderance of the evidence implicating microglia. By
studying these supporting structures, neuropathic pain pharmacologic
targets may in the future include more that the neurons themselves.

Simon Beggs, Michael W. Salter
Drug Development Research, 67(4) :289-301, 2006

Reviewed by UroToday.com Contributing Editor Philip M Hanno, MD, MPH