Future basic science directions into mechanisms of neuropathic pain.
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abstract
The aim of this article is to outline mechanisms underlying generation and maintenance of pain arising from trauma to peripheral nerve fibers and to present an overview of our recent studies of animal models of peripheral neuropathic pain and pain of temporomandibular disorders (TMD). The former model was induced by placing a polyethylene cuff around the sciatic nerve of the Sprague-Dawley rat and the TMD model was induced by injection of complete Freund's adjuvant into the rat's temporomandibular joint. In cuff-implanted rats, ongoing activity of dorsal horn neurons was greater than in controls, the cutaneous receptive field size of the neurons was greater, and both noxious and innocuous mechanical stimuli to the receptive field elicited an excitatory response during stimulation but also a marked afterdischarge that lasted up to 30 minutes; this afterdischarge was never observed in control rats in response to innocuous stimulation. The model of TMD was characterized by joint space narrowing, bone remodeling, infiltration of immune cells, loss in the range of jaw opening, and signs of nociception. Alterations in the neural substrate of nociception in animal models, and therefore also possibly in humans, appear to include changes in peripheral as well as central neurons. In the periphery, changes include alterations in the phenotype and central projections of large-diameter sensory nerve fibers. At the level of the trigeminal brainstem and spinal cord, there appear to be several types of change. One type is an increased efficacy of synaptic transmission onto second-order neurons. Another type of change is a reduction in inhibitory mechanisms, including a shift of gamma-amino butyric acid (GABAA) receptor activation to excitation. There is a need for further studies to focus on mechanisms for either the generation or the maintenance, or both, of neuropathic pain.
