Age-dependent decrease in inhibitory drive on the excitatory superficial spinal dorsal horn neurons.

Area of Science:

• Neuroscience
• Pain Research
• Spinal Cord Physiology

Background:

• Superficial laminae I-II of the spinal dorsal horn (SDH) process pain signals.
• Interneuron interactions in the SDH are critical for pain modulation.
• Age-related increases in pain sensitivity suggest altered SDH circuitry.

Purpose of the Study:

• To investigate age-related changes in SDH intrinsic connectivity.
• To determine if altered inhibitory and excitatory interneuron interactions contribute to age-related pain sensitivity.

Main Methods:

• Utilized Vgat;tdTomato transgenic mice to distinguish inhibitory and excitatory interneurons.
• Compared spontaneous inhibitory postsynaptic currents (sIPSCs) in adult and aged mice.
• Analyzed sIPSC amplitude and frequency in tdTomato+ (inhibitory) and tdTomato- (excitatory) interneurons.

Main Results:

• Adult mice showed higher sIPSC amplitude and frequency in excitatory vs. inhibitory interneurons.
• These differences were abolished in aged mice.
• Aged mice exhibited reduced inhibition in excitatory neurons compared to adults, indicating network disinhibition.

Conclusions:

• Aging alters the balance of excitation and inhibition in the SDH.
• Reduced inhibition of excitatory interneurons in aged mice may underlie increased pain perception.
• Findings suggest age-related disinhibition of the SDH network contributes to heightened pain sensitivity.