Na(v) 1.8-null mice show stimulus-dependent deficits in spinal neuronal activity

Area of Science:

• Neuroscience
• Pain Research
• Ion Channel Physiology

Background:

• The voltage-gated sodium channel Na(v) 1.8 is primarily expressed in nociceptive sensory neurons.
• Na(v) 1.8-null mice exhibit altered pain behaviors, including increased mechanical pain thresholds and deficits in inflammatory and visceral pain.

Purpose of the Study:

• To investigate the functional role of Na(v) 1.8 in pain transmission by recording from dorsal horn neurons in Na(v) 1.8-null mice.
• To understand how Na(v) 1.8 influences the coding of sensory information from the periphery to the spinal cord.

Main Methods:

• In vivo electrophysiology recordings in intact, anesthetized Na(v) 1.8-null mice and littermate controls.
• Stimulation of dorsal horn neurons using a wide range of sensory modalities (mechanical, thermal, electrical).

Main Results:

• Na(v) 1.8-null mice displayed significant deficits in dorsal horn neuronal responses to mechanical stimuli across non-noxious and noxious ranges.
• Responses to other stimuli, such as pinch and brush, were also reduced in Na(v) 1.8-null mice.
• A significant reduction in spontaneous neuronal activity was observed in mice lacking Na(v) 1.8.

Conclusions:

• Deletion of Na(v) 1.8 leads to stimulus-dependent deficits in dorsal horn neuronal coding, particularly for mechanical stimuli.
• These findings suggest Na(v) 1.8 is crucial for, or associated with proteins involved in, mechanosensation.