Highlights
- •Spinal PAR1 plays an important role in the genesis of chronic pain in MRL/lpr mice.
- •Activation of PAR1 and suppression of AMPK activity in MRL/lpr mice with chronic pain.
- •Blockade of PAR1 or AMPK activation attenuated chronic pain in MRL/lpr mice.
- •Targeting the PAR1 and AMPK pathways may be a potent approach for treating chronic pain caused by SLE.
Abstract
Systemic lupus erythematosus (SLE) is an unpredictable autoimmune disease where the
body's immune system mistakenly attacks healthy tissues in many parts of the body.
Chronic pain is one of the most frequently reported symptoms among SLE patients. We
previously reported that MRL lupus prone (MRL/lpr) mice develop hypersensitivity to
mechanical and heat stimulation. In the present study, we found that the spinal protease-activated
receptor-1(PAR1) plays an important role in the genesis of chronic pain in MRL/lpr
mice. Female MRL/lpr mice with chronic pain had activation of astrocytes, over-expression
of thrombin and PAR1, enhanced glutamatergic synaptic activity, as well as suppressed
activity of adenosine monophosphate-activated protein kinase (AMPK) and glial glutamate
transport function in the spinal cord. Intrathecal injection of either the PAR1 antagonist,
or AMPK activator attenuated heat hyperalgesia and mechanical allodynia in MRL/lpr
mice. Furthermore, we also identified that the enhanced glutamatergic synaptic activity
and suppressed activity of glial glutamate transporters in the spinal dorsal horn
of MRL/lpr mice are caused by activation of the PAR1 and suppression of AMPK signaling
pathways. These findings suggest that targeting the PAR1and AMPK signaling pathways
in the spinal cord may be a useful approach for treating chronic pain caused by SLE.
Key Words
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Article info
Publication history
Accepted:
January 3,
2023
Received in revised form:
December 25,
2022
Received:
August 13,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc.
