Neuropathic Pain: Symptoms, Models, And Mechanisms

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Neuropathic Pain: Symptoms, Models, And Mechanisms

http://www.medicalnewstoday.com/medicalnews.php?newsid=65639

Simon Beggs and 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 Aä 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, W. Salter

Drug Development Research, 67(4) :289-301, 2006