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Papers of the Week

Papers: 1 Apr 2023 - 7 Apr 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology

Neuropathic Pain

2023 Apr 04

Mol Pain


Genetic evidence of the function of Phox2a-expressing anterolateral system neurons in the transmission of chronic pain.


Zhang X, Millecamps M, Kania A


The development of the chronic neuropathic pain state often originates at the level of peripheral sensory neurons, whose abnormal function elicits central sensitization and maladaptive plasticity in the nociceptive circuits of the spinal dorsal horn. These changes eventually reach supraspinal areas bringing about cognitive and affective co-morbidities of chronic pain such as anxiety and depression. This transmission presumably relies on the function of spinal projection neurons at the origin of the anterolateral system (AS). However, the identity of these neurons and the extent of their functional contribution remain unknown. Here, we asked these questions in the context of the mouse AS neurons that require the developmental expression of the transcription factor Phox2a for their normal function. Previously, we found that a spinal cord-specific loss of Phox2a (Phox2acKO) in mice disrupts AS neuron connectivity to their supraspinal targets thus attenuating the transmission of acute nociceptive information from the spinal cord to the brain. Here, we examined the effects of a spinal cord-specific loss of Phox2a on the development of central sensitization evoked by the spared nerve injury (SNI) model of chronic pain. We found that Phox2acKO mice with SNI developed normal reflexive spinal responses such as mechanical allodynia evidenced by a decreased withdrawal threshold to von Frey filament stimulation and dynamic brush. On the other hand, Phox2acKO attenuated the development of cold but not mechanical hyperalgesia, in behavioral paradigms that require the relay of nociceptive information to the brain. Furthermore, Phox2acKO attenuated anxio-depressive-like behaviors evoked by SNI, measured by performance in the open field test and tail suspension test. Thus, Phox2a AS neurons play a critical role in the generation and maintenance of chronic neuropathic pain.