Beneficial actions of neurotrophin treatment on diabetes-induced hypoalgesia in mice.
Studies were carried out in streptozotocin-treated diabetic mice to evaluate their behavioral responses to different noxious stimuli. In opposition to rats, streptozotocin-injected diabetic mice display a persistent hypoalgesia to non-noxious mechanical stimulation (von Frey monofilament). Similarly, nocifensive responses of diabetic mice to formalin injection were significantly reduced in both acute and inflammatory phases. However, no overt differences were detected between nondiabetic and diabetic mice in their sensitivity to noxious heat (radiant heat), cold (acetone), or noxious mechanical (pinprick) stimuli applied to the hind paw. To evaluate whether neurotrophin treatment could normalize the sensory deficits, nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was administered intrathecally to diabetic mice for 3 weeks. Neurotrophin-treated mice were also compared to mice that received insulin for 3 weeks. Both NGF and insulin treatment significantly restored mechanical and chemogenic behavioral responses of diabetic mice. In contrast, GDNF treatment only reversed behavioral responses to chemogenic stimuli during the acute phase of the formalin test. These results demonstrate that diabetic mice develop reduced sensitivity to mechanical and chemical stimuli. Furthermore, these studies show that dorsal root ganglion neurons in diabetic mice are responsive to treatment with either NGF or GDNF; however, these 2 neurotrophins differ in their ability to affect distinct somatosensations.
Christianson
Julie A
JA
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Ryals
Janelle M
JM
McCarson
Kenneth E
KE
Wright
Douglas E
DE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D003080:Cold Temperature; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy; D003929:Diabetic Neuropathies / Q000150:complications / Q000188:drug therapy*; D005557:Formaldehyde; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006358:Hot Temperature; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D010146:Pain / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation
D001786:Blood Glucose; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007004:Hypoglycemic Agents; D007328:Insulin; D009414:Nerve Growth Factors; D005557:Formaldehyde