Ventrolateral periaqueductal gray matter integrative system of defense and antinociception

Priscila Medeiros,Gustavo Henrique De Mello Rosa,Yara Bezerra De Paiva,Juliana Almeida Da Silva,Luiz Guilherme S Branco,Alexandre Pinto Corrado,Farhad Ullah,Audrey Franceschi Biagioni,Norberto Cysne Coimbra

doi:10.1007/s00424-022-02672-0

Abstract

Defensive responses are neurophysiological processes crucial for survival during threatening situations. Defensive immobility is a common adaptive response, in rodents, elaborated by ventrolateral periaqueductal gray matter (vlPAG) when threat is unavoidable. It is associated with somatosensory and autonomic reactions such as alteration in the sensation of pain and rate of respiration. In this study, defensive immobility was assessed by chemical stimulation of vlPAG with different doses of NMDA (0.1, 0.3, and 0.6 nmol). After elicitation of defensive immobility, antinociceptive and respiratory response tests were also performed. Results revealed that defensive immobility was followed by a decrease in the nociceptive perception. Furthermore, the lowest dose of NMDA induced antinociceptive response without eliciting defensive immobility. During defensive immobility, respiratory responses were also disturbed. Interestingly, respiratory rate was increased and interspersed with prolonged expiratory phase of breathing. These findings suggest that vlPAG integrates three different defensive behavioral responses, contributing to the most effective defensive strategies during threatening situations.

Highlights

Threatening situations are known to influence defensive behavioral reaction patterns, causing motor and autonomic response expressions to enhance the survival probabilities [14, 20]
Despite the well-reported pre-escape and afterescape defensive immobility elaborated by the periaqueductal gray matter (PAG), the associative somatosensory and autonomic reactions such as pain sensation and respiratory rate organized by ventrolateral periaqueductal gray matter (vlPAG) are not well known yet
Midbrain tegmentum chemical stimulation performed with N-methyl-D-aspartic acid (NMDA) microinjection in vlPAG induced the defensive behavioral response of defensive immobility, alteration in the nociceptive threshold, and pulmonary ventilation

Summary

Introduction

Threatening situations are known to influence defensive behavioral reaction patterns, causing motor and autonomic response expressions to enhance the survival probabilities [14, 20]. The defensive state has been reported to be organized by the ventrolateral periaqueductal gray matter (vlPAG) column [4, 51]. Defensive immobility organized by the vlPAG neurons have been described during several conditions such as contextual fear conditioning [8, 45], prey versus predator paradigm [10], and midbrain tectum electrical and chemical stimulation [47, 48]. Despite the well-reported pre-escape and afterescape defensive immobility elaborated by the periaqueductal gray matter (PAG), the associative somatosensory and autonomic reactions such as pain sensation and respiratory rate organized by vlPAG are not well known yet

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Discussion

Conclusion