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Identifying the pathways required for coping behaviours associated with sustained pain.

Tianwen Huang1,2, Shing-Hong Lin1,2, Nathalie M Malewicz3

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Researchers identified specific spinal neurons that control pain coping behaviors, like licking wounds, in mice. This discovery sheds light on the neural basis of sustained pain responses and challenges how we measure pain.

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Area of Science:

  • Neuroscience
  • Pain Research
  • Somatosensory System

Background:

  • Noxious stimuli elicit distinct reflexive and coping responses in animals and humans.
  • The neural circuits underlying these dual pain responses are not fully understood.
  • Understanding these circuits is crucial for pain management and research.

Purpose of the Study:

  • To identify the specific spinal neural circuits responsible for pain coping behaviors.
  • To investigate the role of TAC1-expressing spinal neurons in mediating responses to sustained pain.
  • To explore the relationship between spinal circuits and medial thalamic nuclei in pain processing.

Main Methods:

  • Utilized genetic tools (TAC1Cre and LBX1Flpo) to target and ablate specific spinal neurons in mice.
  • Assessed behavioral responses to noxious stimuli, including licking, aversion, and reflexive withdrawal.
  • Investigated neural projections from spinal cord to medial thalamic and parabrachial nuclei.
  • Examined the roles of specific primary sensory neurons (MRGPRD and TRPV1) in distinct pain responses.

Main Results:

  • Ablation of spinal neurons co-expressing TAC1 and LBX1 abolished persistent licking and conditioned aversion to sustained pain stimuli.
  • These specific spinal neurons project to the medial thalamic nuclei, directly and indirectly.
  • Reflexive defensive responses remained intact after ablation, indicating a selective role in coping.
  • Primary sensory neurons (MRGPRD and TRPV1) show functional segregation for reflexive versus coping pain behaviors.

Conclusions:

  • Spinal neurons co-expressing TAC1 and LBX1 are critical drivers of pain coping behaviors.
  • A distinct neural pathway involving spinal TAC1-lineage neurons and medial thalamus mediates sustained pain responses.
  • The findings reveal a fundamental subdivision in the somatosensory system for different pain behaviors.
  • Current methods relying solely on reflexive responses may not fully capture the experience of sustained pain.