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Sprouting phenomenon, a new model for the role of A-beta fibers in wind up.

Wind up is a progressive frequency-dependent facilitation of the responses of nociceptive neurons observed on the application of repetitive (usually electrical) stimuli of constant intensity. The NMDA and NK1 receptors are essentially involved in wind up. After induction of wind up, stimulation of C-fibers show the characteristics of wind up, but stimulation of Abeta fibers for induction of wind up is controversial. In this study, we have proposed a new model for the role of Abeta fibers in wind up, through sprouting of nerve fibers in the dorsal horn of spinal cord. We named it "sprouting phenomenon". It has been reported that in some clinical hyperalgesic states induced by peripheral injury or inflammation, wind up may aggravate the pain. For example, studies have indicated the presence of wind up in post-surgical states, some neuropathic pains, fibromyalgia syndrome, and post-herpetic neuralgia. According to sprouting phenomenon, it seems that some clinical interventions can be assessed to alleviate post-inflammatory pains: (1) Immediate and complete relief of inflammation by anti-inflammatory agents to prevent repetitive excitation of C-fibers and subsequent morphological changes of dorsal horn laminae; (2) using local anesthetics in order to prevent pain signal transmission; (3) prevention of sprouting by intrathecal injection of some anti-proliferation agents; (4) using NMDA or NK1 receptor antagonists to prevent central mechanism of wind up. Some clinical trials have indicated the effectiveness of these antagonists. It is worth noting that future clinical studies are needed to validate these predictions.