New findings confirm that many features of neuropathic pain syndromes, including spontaneous pain, mechanical allodynia (pain evoked from stimulation of Abeta low threshold mechanoreceptor (LTM) afferents), and cold hyperalgesia, are found also after experimental intradermal injections of capsaicin, an active ingredient in chili pepper. AbetaLTM- mediated allodynia was supported by differential tourniquet cuff blocks in 4 patients; allodynia and touch sensations were abolished concurrently. In 2 patients we observed spread of spontaneous pain and mechano-allodynia from the site of injury at a lower extremity to include both the contralateral extremity and upper extremities. These symptoms were attenuated or abolished by elevation of the affected extremity for a period of 30-40 minutes, suggesting a central mechanism maintained by a peripheral generator in the affected extremity that is sensitive to changes in local perfusion. Large doses, up to 1000 g, resulted in a long period of 30 min to several hours in which mechano-allodynia was present in the absence of spontaneous pain, suggesting that in the initiation phase the altered central processing responsible for mechano- allodynia can exist autonomously, i.e. in the absence of ongoing peripheral input. This autonomous processing has not been observed in patients. During this autonomous period, interventions such as partial or complete occlusion of circulation produced an intense, widespread spontaneous pain which was not increased by stimulation of sympathetic activity. This pain also was found if the limb was exsanguinated before the cuff block, and it was attenuated if the nociceptive drive was blocked by infiltration of local anesthetic at the injection site, or after a regional block of the arm at the elbow. These results support the hypothesis that a peripheral injury initiates central processes resulting in spontaneous pain and evoked abnormalities such as mechano-allodynia and cold hyperalgesia. At the time of injury, these proceses may exist independently of peripheral input, although putative sources of further input (e.g. tourniquet cuff) can exacerbate symptoms, such as rekindling spontaneous pain. In the maintenance phase after injury (as observed in patients), the central process may expand to include body sites distant from the injury, however this expanded altered processing appears to be maintained dynamically by input from the injury focus.
