Depression has a high rate of
comorbidity with
neuropathic pain. This study aims to investigate the effect of Mygalin, an acylpolyamine synthesized from a natural molecule in the
hemolymph of the Acanthoscurria gomesiana
spider, injected into the prelimbic (PrL) region of the medial
prefrontal cortex on chronic
neuropathic pain and
depression comorbidity in
rats. To investigate that
comorbidity,
neuropathic pain was induced by chronic
constriction injury (CCI) of the
sciatic nerve in
male Wistar rats. The biotinylated biodextran
amine (BDA) bidirectional neural tract tracer was microinjected into the PrL cortex to study
brain connections.
Rodents were further subjected to von Frey (
mechanical allodynia),
acetone (
cold allodynia), and forced swim (depressive-like
behavior) tests. BDA neural tract tracer-labeled perikarya were found in the dorsal columns of the
periaqueductal gray matter (dPAG) and the
dorsal raphe nucleus (DRN). Neuronal activity of DRN
neurons decreased in CCI
rats. However, PrL cortex
treatment with Mygalin increased the number of spikes on DRN
neurons. Mygalin
treatment in the PrL cortex decreased both mechanical and
cold allodynia and immobility
behavior in CCI
rats. PrL cortex
treatment with
N-methyl-D-aspartate (
NMDA) receptor receptors attenuated the
analgesic and antidepressive effects caused by Mygalin. The PrL cortex is connected with the dPAG and DRN, and Mygalin
administration into the PrL increased the activity of DRN
neurons. Mygalin in the PrL cortex produced antinociceptive and antidepressive-like effects, and the
NMDA agonist reversed these effects.