Background: Causes of neuropathic pain following nerve injury remain unclear, limiting the development of\r\nmechanism-based therapeutic approaches. Animal models have provided some directions, but little is known\r\nabout the specific sensory neurons that undergo changes in such a way as to induce and maintain activation of\r\nsensory pain pathways. Our previous studies implicated changes in the Ab, normally non-nociceptive neurons in\r\nactivating spinal nociceptive neurons in a cuff-induced animal model of neuropathic pain and the present study\r\nwas directed specifically at determining any change in excitability of these neurons. Thus, the present study aimed\r\nat recording intracellularly from Ab-fiber dorsal root ganglion (DRG) neurons and determining excitability of the\r\nperipheral receptive field, of the cell body and of the dorsal roots.\r\nMethods: A peripheral neuropathy was induced in Sprague Dawley rats by inserting two thin polyethylene cuffs\r\naround the right sciatic nerve. All animals were confirmed to exhibit tactile hypersensitivity to von Frey filaments\r\nthree weeks later, before the acute electrophysiological experiments. Under stable intracellular recording conditions\r\nneurons were classified functionally on the basis of their response to natural activation of their peripheral receptive\r\nfield. In addition, conduction velocity of the dorsal roots, configuration of the action potential and rate of\r\nadaptation to stimulation were also criteria for classification. Excitability was measured as the threshold to\r\nactivation of the peripheral receptive field, the response to intracellular injection of depolarizing current into the\r\nsoma and the response to electrical stimulation of the dorsal roots.\r\nResults: In control animals mechanical thresholds of all neurons were within normal ranges. Ab DRG neurons in\r\nneuropathic rats demonstrated a mean mechanical threshold to receptive field stimulation that were significantly\r\nlower than in control rats, a prolonged discharge following this stimulation, a decreased activation threshold and a\r\ngreater response to depolarizing current injection into the soma, as well as a longer refractory interval and delayed\r\nresponse to paired pulse electrical stimulation of the dorsal roots.\r\nConclusions: The present study has demonstrated changes in functionally classified Ab low threshold and high\r\nthreshold DRG neurons in a nerve intact animal model of peripheral neuropathy that demonstrates nociceptive\r\nresponses to normally innocuous cutaneous stimuli, much the same as is observed in humans with neuropathic\r\npain. We demonstrate further that the peripheral receptive fields of these neurons are more excitable, as are the\r\nsomata. However, the dorsal roots exhibit a decrease in excitability. Thus, if these neurons participate in\r\nneuropathic pain this differential change in excitability may have implications in the peripheral drive that induces\r\ncentral sensitization, at least in animal models of peripheral neuropathic pain, and Ab sensory neurons may thus\r\ncontribute to allodynia and spontaneous pain following peripheral nerve injury in humans.
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