Basolateral amygdala astrocytes modulate of diabetic neuropathic pain
and may be a potential therapeutic target for koumine
Background and Purpose: New remedies are required for the treatment of
diabetic neuropathic pain (DNP) due to insufficient efficacy of
available therapies. Here, we used chemogenetic approaches combined with
in vivo pharmacology to elucidate the role of BLA astrocytes in DNP
pathogenesis and provide new insights into DNP therapeutic strategies.
Experimental Approach: A streptozotocin-induced DNP model was
established. Designer receptors exclusively activated by designer drugs
(DREADDs) were used to regulate the activity of astrocytes. Mechanical
hyperalgesia was assessed using the electronic von Frey test.
Anxiety-like behaviors were detected by open field and elevated plus
maze tests. Astrocytic activity was detected by immunofluorescence, and
cytokine content was determined by ELISA. Key Results: BLA astrocytes
were regulated by DREADDs, and inhibition of BLA astrocytes attenuated
mechanical allodynia and anxiety-like behavior in DNP rats.
Contrastively, temporary activation of BLA astrocytes induced allodynia
without anxious behavior in naive rats. In addition, we found that
koumine alleviates mechanical allodynia and anxiety-like behavior in DNP
rats, inhibits the activation of BLA astrocytes and suppresses the
inflammatory response. Furthermore, persistent activation of BLA
astrocytes by chemogenetic mimics chronic pain, and koumine can
alleviate its pain hypersensitivity and anxiety-like behavior.
Conclusion and Implications: DREADDs bidirectionally regulate the
activity of BLA astrocytes, which proves for the first time the role of
BLA astrocytes activation in the pathogenesis of DNP and represents a
novel therapeutic strategy for DNP. Koumine ameliorated DNP, perhaps by
inhibiting the activation of BLA astrocytes and reveal KM as a potential
candidate for treating DNP.