(289) Divergent roles of periaqueductal gray GABAergic and glutamatergic neurons in modulation of nociceptive information

Abstract

The periaqueductal gray (PAG), a well-conserved neurosubstrate, is thought to regulate several complex behaviors including pain perception. A role for the PAG in pain processing is supported by multiple lines of investigation, including the finding that gross electrical activation of PAG can produce analgesia. However, the PAG contains numerous molecularly undefined neuronal populations that receive various neural inputs, and thus the distinct neuronal populations within the PAG that selectively mediate specific aspects of analgesia remain poorly understood. Therefore, we sought to study the effects of modulating the activity of subsets of neurons in the PAG on pain processing using cell type-specific chemogenetic manipulations. We found that gross chemogenetic inhibition (Gi) of PAG neurons resulted in development of thermal and mechanical hypersensitivity, whereas chemogenetic activation (Gq) of PAG neurons resulted in increased paw withdrawal latencies and paw withdrawal thresholds to thermal and mechanical stimuli. Cell type specific chemogenetic inhibition (Gi) of PAG GABAergic neurons resulted in increased paw withdrawal latencies and paw withdrawal thresholds to thermal and mechanical stimuli. We also found that chemogenetic activation (Gq) of PAG glutamatergic neurons also resulted in increased paw withdrawal latencies and paw withdrawal thresholds to thermal and mechanical stimuli. These studies give unique insight into the precise role of PAG GABAergic and glutamatergic neurons in nociceptive processing. The periaqueductal gray (PAG), a well-conserved neurosubstrate, is thought to regulate several complex behaviors including pain perception. A role for the PAG in pain processing is supported by multiple lines of investigation, including the finding that gross electrical activation of PAG can produce analgesia. However, the PAG contains numerous molecularly undefined neuronal populations that receive various neural inputs, and thus the distinct neuronal populations within the PAG that selectively mediate specific aspects of analgesia remain poorly understood. Therefore, we sought to study the effects of modulating the activity of subsets of neurons in the PAG on pain processing using cell type-specific chemogenetic manipulations. We found that gross chemogenetic inhibition (Gi) of PAG neurons resulted in development of thermal and mechanical hypersensitivity, whereas chemogenetic activation (Gq) of PAG neurons resulted in increased paw withdrawal latencies and paw withdrawal thresholds to thermal and mechanical stimuli. Cell type specific chemogenetic inhibition (Gi) of PAG GABAergic neurons resulted in increased paw withdrawal latencies and paw withdrawal thresholds to thermal and mechanical stimuli. We also found that chemogenetic activation (Gq) of PAG glutamatergic neurons also resulted in increased paw withdrawal latencies and paw withdrawal thresholds to thermal and mechanical stimuli. These studies give unique insight into the precise role of PAG GABAergic and glutamatergic neurons in nociceptive processing.