Layer-specific pain relief pathways originating from primary motor cortex

A new study in mice has helped illuminate how the brain’s primary motor cortex (M1) – a brain region most commonly associated with control of motor functions – helps suppress dimensions of neuropathic pain.

The findings suggest a causal link between this brain region and pain control and could inform new neurostimulation therapies for chronic pain management. Area M1 has been extensively studied with respect to neuronal circuitry that initiates bodily movements.

Unexpectedly, this brain region is known to undergo neural change when humans perceive pain; the interactions between pain and motor functions have been used in exercise therapies for pain management. Despite this, very little is known about the neurobiological basis for the role of M1 in modulating pain perception.

To better understand this link, the researchers used a suite of approaches, including viral mapping, in vivo imaging, electrophysiology, and layer- and cell type-specific optogenetic and chemogenetic manipulations to investigate the neuronal circuits and mechanisms involved in the modulation of sensory and emotional components of neuropathic pain in mice.

The authors found that distinct layer-specific neuronal circuits in M1 alter both the sensory functions and emotional states associated with chronic pain. According to the findings, activation of a pathway connecting layer 5 M1 neurons to specific populations of cells in the brain’s zona incerta and periaqueductal grey suppressed sensory hypersensitivity to pain in the mice.

In addition, activation of another circuit, this one connecting layer 6 M1 neurons to the nucleus accumbens, reduced the negative emotional and behavioral components of neuropathic pain.

These insights, say the authors, will help provide insights for developing and improving neurostimulation therapies for optimal pain control.