Mechanical hyperalgesia in rats with chronic perfusion of lumbar dorsal root ganglion with hyperglycemic solution

In diabetes, chronic systemic hyperglycemia is associated with pain and oth er symptoms of peripheral neuropathy. Evaluation of mechanisms causing thes e symptoms is complicated because of the overlap between the systemic effec ts of hyperglycemia and its toxic effects within the peripheral nervous sys tem. To address this problem we developed a technique for chronic local in vivo perfusion of rat lumbar dorsal root ganglion (DRG) with a hyperglycemi c solution. Osmotic pumps were filled with 30 mM glucose in physiological b uffer and implanted in normal adult rats. The output of the catheter attach ed to the pump was positioned in a hole drilled through the right transvers e process of the L-5 vertebrae to perfuse the corresponding DRG. Repetitive tests of foot withdrawal to mechanical stimuli have shown that chronic hyp erglycemia localized to the L5 DRG causes hyperalgesia in the hind limb inn ervated by perfused ganglion but not in the contralateral limb. Control exp eriments (DRG perfusion with 5 mM glucose or 5 mM glucose + 25 mM mannitol solution) have shown that hyperglycemia-induced hyperalgesia can not be att ributed to surgery-related injury or hyperosmolality of the ganglion-perfus ing solution. These data demonstrate direct functional toxicity of hypergly cemia in the peripheral nervous system. This technique provides a new appro ach for in vivo study of chronic effects of physiologically active factors on DRG neuron function. (C) 2001 Elsevier Science B.V. All rights reserved.