Neuropathic Pain Causes Pyramidal Neuronal Hyperactivity in the Anterior Cingulate Cortex

Area of Science:

• Neuroscience
• Pain Research
• Somatosensory System

Background:

• The anterior cingulate cortex (ACC) plays a role in acute and chronic pain processing.
• Understanding ACC neuronal activity during chronic pain states, particularly after nerve injury, remains incomplete.
• Investigating sensory processing in the ACC under neuropathic pain conditions is crucial.

Purpose of the Study:

• To investigate the response of ACC neurons to sensory stimulation in the context of neuropathic pain.
• To characterize the activity patterns of layer 5 (L5) pyramidal neurons in the dorsal ACC.
• To determine the bilateral involvement of the ACC in response to peripheral noxious stimuli and neuropathic pain.

Main Methods:

• Utilized in vivo two-photon calcium imaging in awake, head-restrained mice.
• Monitored somatic activity of individual L5 pyramidal neurons in the dorsal ACC.
• Applied peripheral noxious stimuli to hind paws to assess neuronal responses.

Main Results:

• Dorsal ACC L5 pyramidal neurons exhibited robust activity in response to noxious stimuli, correlating with stimulus intensity.
• Noxious stimulation of either hind paw evoked bilateral activation of ACC neurons.
• Following nerve injury-induced neuropathic pain, L5 pyramidal neurons in both ACC sides showed heightened activity, irrespective of direct pain stimuli.

Conclusions:

• Layer 5 pyramidal neurons in the bilateral ACC are hyperactive during the development of neuropathic pain.
• The ACC demonstrates significant bilateral involvement in processing pain information, even in chronic pain states.
• These findings provide insights into the neural mechanisms underlying chronic pain perception in the ACC.