The critical role of amygdala subnuclei in nociceptive and depressive-like behaviors in peripheral neuropathy

Author(s)

Seno, Midia D. J. ^[1] ; Assis, Danielle V. ^[1] ; Gouveia, Flavia ^[1] ; Antunes, Geiza F. ^[1] ; Kuroki, Mayra ^[1] ; Oliveira, Caroline C. ^[1] ; Santos, Lennon C. T. ^[1] ; Pagano, Rosana L. ^[1] ; Martinez, Raquel C. R. ^[1]

Affiliation

^[1] Hosp Sirio Libanes, Lab Neurosci, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, SEP 11 2018.
• Web of Science Citations: 6

Abstract

The amygdala is an important component of the limbic system that participates in the control of the pain response and modulates the affective-motivational aspect of pain. Neuropathic pain is a serious public health problem and has a strong affective-motivational component that makes it difficult to treat. The central (CeA), basolateral (BLA) and lateral (LA) nuclei of the amygdala are involved in the processing and regulation of chronic pain. However, the roles of these nuclei in the maintenance of neuropathic pain, anxiety and depression remain unclear. Thus, the main objective of this study was to investigate the role of amygdala subnuclei in the modulation of neuropathic pain, including the affective-motivational axis, in an experimental model of peripheral neuropathy. The specific goals were as follows: (1) To evaluate the nociceptive responses and the patterns of activation of the CeA, BLA and LA in neuropathic rats; and (2) To evaluate the effect of inactivating the amygdala nuclei on the nociceptive response, anxiety and depressive behaviors, motor activity, and plasma stress hormones in animals with neuropathic pain. Thus, mechanical hyperalgesia and allodynia, and the pattern of c-Fos staining in the amygdala subnuclei were evaluated in rats with chronic constriction of the sciatic nerve, as well as sham-operated and naive rats. Once the amygdala subnuclei involved in neuropathic pain response were defined, those subnuclei were pharmacological inactivated. The effect of muscimol inactivation on the nociceptive response (hyperalgesia and allodynia), anxiety (elevated plus-maze), depressive-like behavior (forced swim test), motor activity (open field), and plasma stress hormone levels (corticosterone and adrenocorticotropic hormone) were evaluated in sham-operated and neuropathic animals. The results showed that the anterior and posterior portions of the BLA and the central portion of the CeA are involved in controlling neuropathic pain. The inactivation of these nuclei reversed hyperalgesia, allodynia and depressive-like behavior in animals with peripheral neuropathy. Taken together, our findings improve our understanding of the neurocircuitry involved in persistent pain and the roles of specific amygdala subnuclei in the modulation of neuropathic pain, including the neurocircuitry that processes the affective-motivational component of pain. (AU)

• FAPESP's process: 15/26079-8 - Participation of descending serotonergic analgesia pathway and changes in inflammatory and neurodegenerative response in the treatment of neuropathic pain by transcranial direct-current stimulation
• Grantee: Rosana de Lima Pagano
• Support type: Regular Research Grants
• FAPESP's process: 11/08575-7 - The role of dopaminergic modulation in the lateral nucleus of amygdala during active avoidance response
• Grantee: Raquel Chacon Ruiz Martinez
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 13/20602-5 - Prospective analyses of the functional results of philanthropist bilateral amygdalectomy in patients with refractory aggression
• Grantee: Flavia Venetucci Gouveia
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/12999-5 - Lineage factor evaluation of aversive learning test anxiety levels in good and bad performance animals: Wistar versus Sprague Dawley
• Grantee: Lennon Tosati Cardoso Dos Santos
• Support type: Scholarships in Brazil - Scientific Initiation