Norepinephrine Rekindles Mechanical Allodynia in Sympathectomized Neuropathic Rat

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Abstract
Background: Sympathectomy is believed to be the most effective means to relieve pain in sympathetically maintained pain (SMP). This suggests that there is an abnormal interaction between the somatosensory and sympathetic nervous systems, which plays an important role in the generation of pain in SMP. However, it is not clear where the interaction between the two systems occurs. Purpose: The purpose of this study was to examine a possible interaction between sensory receptor terminals and the adrenergic system in SMP using a rat neuropathic pain model. Methods: Under halothane anesthesia, neuropathic injury was produced by tightly ligating the left L5/L6 spinal nerves of rats. These animals displayed well-developed behavioral signs of mechanical allodynia that were abolished by a bilateral lumbar sympathectomy performed 1 week later. Then small doses of norepinephrine (NE) were injected subcutaneously into the previously allodynic area of the paw. Results: Subcutaneous injection of NE rekindled signs of mechanical allodynia lasting up to 35 min in a dose-related manner. The increased sensitivity to mechanical stimulation was limited to the area of injected NE spread as determined by dye injection. Conclusions: The data suggest that the sympathetic nervous system interacts with the somatosensory system at the sensory receptor level and this interaction is a part of underlying mechanisms for the generation of allodynia in SMP.

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