A spinal neural circuitry for converting touch to itch sensation

Area of Science:

• Neuroscience
• Spinal Cord Research
• Sensory Biology

Background:

• Touch and itch are vital sensations influencing defensive and emotional behaviors.
• Light touch can paradoxically lead to itch (mechanical itch or alloknesis).
• The spinal cord circuitry for converting touch to itch is not well understood.

Purpose of the Study:

• To elucidate the neural substrates responsible for converting innocuous touch into itch sensations in the spinal cord.
• To identify specific interneurons involved in the touch-to-itch pathway.

Main Methods:

• Utilized genetic targeting of Tachykinin 2-Cre (Tac2^Cre) interneurons in mice.
• Investigated neural connections using Aβ low threshold mechanoreceptor (LTMR) input and GRPR neurons.
• Employed ablation and chemogenetic inhibition techniques to assess functional roles.
• Examined responses to mechanical itch, chemical itch, and noxious touch stimuli.

Main Results:

• Tac2^Cre interneurons receive direct LTMR input and connect to GRPR neurons.
• Ablation or inhibition of Tac2^Cre neurons significantly reduced mechanical itch.
• These manipulations did not affect acute chemical itch or noxious touch.
• GRPR neuron ablation also abolished mechanical itch, indicating convergence.
• Tac2^Cre neuron inhibition impaired chronic dry skin itch, a chemical itch model.

Conclusions:

• Innocuous touch and chemical itch signals converge on GRPR neurons in the spinal cord.
• A specific spinal circuitry involving Tac2^Cre interneurons is crucial for converting touch to itch.
• This circuitry provides a mechanism for the sensation of mechanical itch.