Identifying the pathways required for coping behaviours associated with sustained pain

Tianwen Huang, Shing-Hong Lin, Nathalie M. Malewicz, Yan Zhang, Ying Zhang, Martyn Goulding, Robert H. LaMotte and Qiufu Ma ()
Additional contact information
Tianwen Huang: Harvard Medical School
Shing-Hong Lin: Harvard Medical School
Nathalie M. Malewicz: Yale University School of Medicine
Yan Zhang: Harvard Medical School
Ying Zhang: Harvard Medical School
Martyn Goulding: The Salk Institute for Biological Studies
Robert H. LaMotte: Yale University School of Medicine
Qiufu Ma: Harvard Medical School

Nature, 2019, vol. 565, issue 7737, 86-90

Abstract: Abstract Animals and humans display two types of response to noxious stimuli. The first includes reflexive defensive responses that prevent or limit injury; a well-known example of these responses is the quick withdrawal of one’s hand upon touching a hot object. When the first-line response fails to prevent tissue damage (for example, a finger is burnt), the resulting pain invokes a second-line coping response—such as licking the injured area to soothe suffering. However, the underlying neural circuits that drive these two strings of behaviour remain poorly understood. Here we show in mice that spinal neurons marked by coexpression of TAC1Cre and LBX1Flpo drive coping responses associated with pain. Ablation of these spinal neurons led to the loss of both persistent licking and conditioned aversion evoked by stimuli (including skin pinching and burn injury) that—in humans—produce sustained pain, without affecting any of the reflexive defensive reactions that we tested. This selective indifference to sustained pain resembles the phenotype seen in humans with lesions of medial thalamic nuclei1–3. Consistently, spinal TAC1-lineage neurons are connected to medial thalamic nuclei by direct projections and via indirect routes through the superior lateral parabrachial nuclei. Furthermore, the anatomical and functional segregation observed at the spinal level also applies to primary sensory neurons. For example, in response to noxious mechanical stimuli, MRGPRD- and TRPV1-positive nociceptors are required to elicit reflexive and coping responses, respectively. Our study therefore reveals a fundamental subdivision within the cutaneous somatosensory system, and challenges the validity of using reflexive defensive responses to measure sustained pain.

Keywords: Sustained Pain; Lateral Parabrachial Nucleus; MrgprD; Skin Pinch; Generalized Labelled Magnitude Scale (GLMS) (search for similar items in EconPapers)
Date: 2019
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DOI: 10.1038/s41586-018-0793-8

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