What question did this study set out to answer?

To investigate how the medial orbitofrontal cortex (mOFC) is involved in the relationship between chronic pain and emotional disturbances.

March 21, 2026The Journal of Headache and Pain1 citationsOpen Access

The medial orbitofrontal cortex mediates neuropathic pain and anxiodepressive-like behaviors via two distinct pathways

ZLZhixiao Li TSTianen Si LGLiangliang Gao

Key Points

To investigate how the medial orbitofrontal cortex (mOFC) is involved in the relationship between chronic pain and emotional disturbances.
Inhibition of mOFC glutamatergic neurons was applied following nerve injury.
Assessment of pain hypersensitivity and anxiodepressive-like behaviors was conducted post-intervention.
Pathways involving mOFCCaMKIIα-MD and mOFCCaMKIIα-BLA were examined for their distinct roles.
Inhibition of mOFC glutamatergic neurons reduced pain hypersensitivity.
Anxiodepressive-like behaviors were also mitigated after the inhibition of mOFC neurons.
The mOFCCaMKIIα-MD and mOFCCaMKIIα-BLA pathways independently influenced pain and emotional responses.

Abstract

The present study has revealed that the critical involvement of mOFC glutamatergic neurons in the comorbidity of chronic pain and affective disturbances. Inhibition of mOFC glutamatergic neurons attenuates both pain hypersensitivity and anxiodepressive-like behaviors after nerve injury. The discrete mOFCCaMKIIα-MD and mOFCCaMKIIα-BLA pathway independently control the sensory and affective components of neuropathic pain.

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