Selective changes in nocifensive behavior despite normal cutaneous axon innervation in leptin receptor–null mutant (db/db) mice
| Autor: | Megan S. Johnson, Douglas E. Wright, Susan E. Smittkamp, Janelle M. Ryals, Melinda G. Arnett |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Pain Mice Internal medicine Diabetes mellitus medicine Animals Obesity Axon Pain Measurement Skin Mice Knockout Leptin receptor business.industry General Neuroscience medicine.disease Streptozotocin Axons Mice Mutant Strains Sensory neuron Endocrinology medicine.anatomical_structure Peripheral neuropathy Diabetes Mellitus Type 2 Hyperglycemia Peripheral nervous system Chronic Disease Receptors Leptin Female Neurology (clinical) Cutaneous innervation business medicine.drug |
| Zdroj: | Journal of the Peripheral Nervous System. 12:250-261 |
| ISSN: | 1529-8027 1085-9489 |
| DOI: | 10.1111/j.1529-8027.2007.00144.x |
| Popis: | Much of our understanding of the effects of diabetes on the peripheral nervous system is derived from models induced by streptozotocin in which hyperglycemia is rapidly caused by pancreatic beta-cell destruction. Here, we have quantified sensory impairments over time in leptin receptor (lepr)–null mutant (−/−) mice, a type 2 model of diabetes in which the absence of leptin receptor signaling leads to obesity and chronic hyperglycemia by 4 weeks of age. To assess these mice as a model for peripheral neuropathy, we quantified the responsiveness of lepr (−/−) mice to mechanical, thermal, and chemogenic stimuli, as well as epidermal and dermal innervation of the hind paw. Compared with wild-type (+/+) and heterozygous (+/−) mice, lepr (−/−) mice displayed reduced sensitivity to mechanical stimuli by 6 weeks of age, and however, responses to noxious heat were normal. Lepr (−/−) mice also devoted less activity to their injected paw during the second phase following formalin administration. However, epidermal and dermal innervation of lepr (−/−) mice was not different from that of lepr (+/+) and (+/−) mice even after 10 weeks of hyperglycemia, suggesting that cutaneous innervation is resistant to chronic hyperglycemia in these mice. These results suggest that certain rodent nocifensive behaviors may be linked to the abundance of cutaneous innervation, while others are not. Finally, these results reveal that the lepr (−/−) mice may not be useful to study neuropathy associated with distal axonal degeneration but may be better suited for studies of hyperglycemia-induced sensory neuron dysfunction without distal nerve loss. |
| Databáze: | OpenAIRE |
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