Neuropathic pain - from mechanisms to mechanism-based treatment

Clinical characteristics of neuropathic pain, i.e. pain after nervous system lesions, are burning spontaneous pain, shooting pain attacks and evoked pains. Partly interacting pathophysiological mechanisms at the peripheral and central nervous system may be responsible far initiation and mantainance of chronic neuropathic pain. (1) Peripheral nociceptive fibers can be abnormally sensitized. (2) Central nociceptive second order neurons in the spinal cord dorsal horn can also be sensitized, 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 central nociceptive neurons and may subsequently induce synaptic reorganization in the dorsal horn. By this mechanism activity in mechanosensitive neurons may be perceived as painful. (4) Peripheral nerve injury may induce a pathological interaction of the nociceptive system and the efferent sympathetic system. The different mechanisms can operate in concert in a single disease entity (e.g., postherpetic neuralgia) and also in one single patient. Distinct pathophysiological mechanisms lead to specific sensory symptoms (e.g., dynamic mechanical allodynia, cold hyperalgesia). Therefore, a thorough analysis of sensory symptoms may reveal the underlying mechanisms that are mainly active in a particular patient. In the next step novel drugs will be developed that address specifically the relevant mechanism combination. Drug therapies that are available today include NSAIDS, opioids, tricyclic antidepressants, anticonvulsives (carbamazepine, gabapentin), GABA-agonists, Capsaicin and NMDA-antagonists.