Neuropathic Pain: Symptoms, Models, And Mechanisms
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
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