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Acanthoscurria gomesiana spider-derived Mygalin in the prelimbic prefrontal cortex modulates neuropathic pain and depression comorbid |
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| Authors: | Ana Carolina Medeiros Priscila Medeiros Rafael Naime Ruggiero Danilo De Gregorio Gabriella Gobbi Pedro Ismael Silva Júnior Wagner Ferreira dos Santos Norberto Cysne Coimbra Renato Leonardo de Freitas |
| Institution: | 1. Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), 2. Multi-User Center of Neuroelectrophysiology, Ribeirão Preto, São Paulo, Brazil
Laboratory of Neuroscience of Pain & Emotions, Department of Surgery and Anatomy, FMRP-USP, Ribeirão Preto, São Paulo, Brazil Department of General and Specialized Nursing, Ribeirão Preto Nursing School of the University of São Paulo (EERP-USP), Ribeirão Preto, Brazil Department of Neuroscience and Behavioral Sciences, FMRP-USP, Ribeirão Preto, São Paulo, Brazil;3. Multi-User Center of Neuroelectrophysiology, Ribeirão Preto, São Paulo, Brazil Laboratory of Neuroscience of Pain & Emotions, Department of Surgery and Anatomy, FMRP-USP, Ribeirão Preto, São Paulo, Brazil Department of General and Specialized Nursing, Ribeirão Preto Nursing School of the University of São Paulo (EERP-USP), Ribeirão Preto, Brazil Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, FMRP-USP, Ribeirão Preto, São Paulo, Brazil Interdisciplinary Center for Pain Care, Federal University of São Carlos (UFSCar), São Carlos, São Paulo, Brazil;4. Department of Neuroscience and Behavioral Sciences, FMRP-USP, Ribeirão Preto, São Paulo, Brazil Epilepsy Research Laboratory, Department of Neuroscience and Behavioural Sciences, FMRP-USP, Ribeirão Preto, São Paulo, Brazil;5. Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital, Milan, Italy Department of Psychiatry, Neurobiological Psychiatry Unit, 6. Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada;7. Department of Psychiatry, Neurobiological Psychiatry Unit, 8. Laboratory for Applied Toxinology (LETA) - Center of Toxins, Immune-Response and Cell Signaling – CeTICS/CEPID, Butantan Institute, Sao Paulo, Brazil;9. Neurobiology and Venoms Laboratory, Department of Biology, Ribeirão Preto School of Philosophy, Sciences and Literature of the University of São Paulo (FFCLRP-USP), Ribeirão Preto, São Paulo, Brazil;10. Laboratory of Neuroscience of Pain & Emotions, Department of Surgery and Anatomy, FMRP-USP, Ribeirão Preto, São Paulo, Brazil Department of Neuroscience and Behavioral Sciences, FMRP-USP, Ribeirão Preto, São Paulo, Brazil Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, FMRP-USP, Ribeirão Preto, São Paulo, Brazil Behavioural Neurosciences Institute (INeC), Ribeirão Preto, São Paulo, Brazil;11. Multi-User Center of Neuroelectrophysiology, Ribeirão Preto, São Paulo, Brazil |
| Abstract: | 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. |
| Keywords: | acylpoliamine analgesia chronic neuropathic pain depression glutamatergic system Mygalin prelimbic prefrontal cortex |