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 other symptoms of peripheral neuropathy. Evaluation of mechanisms causing these symptoms is complicated because of the overlap between the systemic effects of hyperglycemia and its toxic effects within the peripheral nervous system. To address this problem we developed a technique for chronic local in vivo perfusion of rat lumbar dorsal root ganglion (DRG) with a hyperglycemic solution. Osmotic pumps were filled with 30 mM glucose in physiological buffer and implanted in normal adult rats. The output of the catheter attached to the pump was positioned in a hole drilled through the right transverse process of the L(5) vertebrae to perfuse the corresponding DRG. Repetitive tests of foot withdrawal to mechanical stimuli have shown that chronic hyperglycemia localized to the L(5) DRG causes hyperalgesia in the hind limb innervated by perfused ganglion but not in the contralateral limb. Control experiments (DRG perfusion with 5 mM glucose or 5 mM glucose+25 mM mannitol solution) have shown that hyperglycemia-induced hyperalgesia can not be attributed to surgery-related injury or hyperosmolality of the ganglion-perfusing solution. These data demonstrate direct functional toxicity of hyperglycemia in the peripheral nervous system. This technique provides a new approach for in vivo study of chronic effects of physiologically active factors on DRG neuron function.
Dobretsov
M
M
Department of Pharmacology and Toxicology, Slot 611, University of Arkansas for Medical Sciences, 4301 West Markham St., Little Rock, AR 72205-7101, USA. dobretsovmaxim@uams.edu
Hastings
S L
SL
Stimers
J R
JR
Zhang
J M
JM
D000818:Animals; D002908:Chronic Disease; D003929:Diabetic Neuropathies / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000503:physiopathology*; D005947:Glucose / Q000633:toxicity*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology*; D006943:Hyperglycemia / Q000139:chemically induced* / Q000503:physiopathology*; D007260:Infusion Pumps / Q000592:standards; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009994:Osmolar Concentration; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010477:Perfusion / Q000295:instrumentation / Q000379:methods*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley
D005947:Glucose