Abstract
Background
The mechanism for reduced pain sensitivity associated with Alzheimer's disease (AD) has not been illustrated. We hypothesize that amyloid beta 1-42 (Aβ1-42) in the spinal cord acts as an endogenous analgesic peptide to suppress pain induced by nerve injury.
Methods
We used chronic constriction injury of the sciatic nerve (CCI) to produce neuropathic pain in Sprague-Dawley rats. ELISA and immunohistochemistry were used to determine the level of Aβ1-42, the expression of Wnt3a/5b, and glial activation in the spinal cord. Western blotting was used to determine the expression of interleukins, the phosphorylation of NR2B and ERK1/2, and the nuclear accumulation of transcriptional factors YAP/TAZ. Thermal hyperalgesia and mechanical allodynia were assessed after CCI and pharmacological manipulations through intrathecal administration.
Results
Nerve injury increases spinal level of Aβ1-42, while intrathecal administration of MK-8931 reduces the level of Aβ1-42 and facilitates mechanical allodynia. Intrathecal administration of Aβ1-42 suppresses pain behaviors in the early and late phases of neuropathy. Spinal administration of Aβ1-42 regulates the expression of interleukins, reducing glial activation and phosphorylation of NR2B and ERK1/2 in the spinal cord of CCI rats. Furthermore, intrathecal administration of Aβ1-42 decreases Wnt5b expression and suppresses the nuclear accumulation of YAP and TAZ. Blocking the interaction between Aβ1-42 and Frizzled receptors by cSP5 reverses the analgesic effects of Aβ1-42.
Conclusions
These findings suggest that spinal Aβ1-42 acts as an endogenous analgesic peptide through regulating cytokines and Wnt pathways. This study may provide a potential target for the development of novel analgesic peptides.
from Wiley: European Journal of Pain: Table of Contents https://ift.tt/3Bj60ed
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