| First Author | Shukla M | Year | 2013 |
| Journal | Neuroscience | Volume | 250 |
| Pages | 92-101 | PubMed ID | 23850592 |
| Mgi Jnum | J:207047 | Mgi Id | MGI:5554338 |
| Doi | 10.1016/j.neuroscience.2013.06.064 | Citation | Shukla M, et al. (2013) Reduced expression of pain mediators and pain sensitivity in amyloid precursor protein over-expressing CRND8 transgenic mice. Neuroscience 250:92-101 |
| abstractText | beta-Amyloid (Abeta) peptides are derived from the sequential cleavage of the amyloid precursor protein (APP). They are enriched in plaques present in Alzheimer's brains and thus play important roles in the pathogenesis of this disease. APP is also known to be expressed in the neurons of dorsal root ganglion (DRG) and contributes to neuronal survival and axonal growth during development. However, whether APP and Abeta peptides are involved in nociception and pathological pain states is mostly unknown. In the present study, we have used behavioral, biochemical and morphological approaches to address this issue in both adult rats and APP over-expressing CRND8 transgenic mice. We observed that the Abeta peptide (17-24) was predominantly expressed in small-sized DRG neurons of rats. Following intraplantar (i.pl.) injection of complete Freud's adjuvant (CFA), the levels of APP and Abeta peptides were significantly reduced in the ipsilateral lumbar 4-6 rat DRG. In 3-, 12- and 24-month-old CRND8 mice, pain sensitivity in response to heat and mechanical stimulation was significantly dampened compared to their age-matched wild-type littermates. In parallel with reduced pain sensitivity, the expression of pain mediators such as substance P, calcitonin gene-related peptide and transient receptor potential vanilloid-1 was significantly reduced in L4-6 DRG of CRND8 mice. Although i.pl. injection of CFA induced a rather similar pattern of inflammatory pain in 3-month-old CRND8 mice and their wild-type littermates, recovery from inflammatory pain seemed faster in 12-month-old CRND8 mice than wild-type mice. These findings suggest that APP and Abeta peptides suppress both nociception and inflammatory pain and are likely involved in blunt pain perception of Alzheimer's patients in clinical settings. |
