Neuropathic pain - Pathophysiological concepts, predictors and new therapies

Clinical characteristics of neuropathic pain syndromes, i.e. pain after nervous system lesions, are burning spontaneous pain, shooting pain attacks and evoked pain. Partly interacting pathophysiological mechanisms at the peripheral and central nervous system may be responsible for initiation and maintenance of chronic neuropathic pain. 1, Peripheral nociceptive fibres can become abnormally sensitised. 2. Central nociceptive ''second order'' neurons in the spinal cord dorsal horn can also be sensitised, i.e. they are hyperexcitable and start responding to non-noxious stimuli. 3. Degeneration of nociceptive neurons may trigger anatomical sprouting of low-threshold mechanosensitive terminals to form connections with central nociceptive neurons and may subsequently induce functional synaptic reorganisation in the dorsal horn. By this mechanism activity in mechanosensitive neurons may be perceived as a painful sensation. 4. Neurotrophins released after nerve injury and in particular after tissue inflammation may also lead to peripheral and central sensitisation of the nociceptive system. 5. Peripheral nerve injury may induce a pathological interaction of the nociceptive system and the efferent sympathetic system. Besides therapy with NSAIDS, opioids, tricyclic antidepressants, anticonvulsants, GABA-agonists, TENS and sympathetic blockade, new therapeutic strageties are now being tested, i.e. capsaicin, new anticonvulsive drugs and NMDA antagonists.