What question did this study set out to answer?

To synthesize current evidence on shared neurochemical mechanisms, primarily neurotransmitter and neuropeptide dysregulation, that drive the bidirectional relationship between chronic pain and depression.

October 3, 2025Frontiers in Molecular NeuroscienceOpen Access

Neurochemical crossroads: exploring the neurotransmitter network in chronic pain and depression comorbidity

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Authors

MMM MaShanxi Agricultural University YZYue ZhangFudan University KTKunming TaoSecond Military Medical University

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Implication

Narrative review reveals shared neurochemical dysregulation in chronic pain and depression comorbidity, highlighting targeted neurotransmitter pathways for coordinated therapy.

Key Points

To synthesize current evidence on shared neurochemical mechanisms, primarily neurotransmitter and neuropeptide dysregulation, that drive the bidirectional relationship between chronic pain and depression.
Reviewed recent preclinical and clinical findings exploring molecular pathways involved in the comorbidity of chronic pain and depressive disorders.
Analyzed the roles of excitatory and inhibitory neurotransmitters, endogenous opioid signaling, and regulatory neuropeptides across pain and emotional pathways.
Elevated glutamate-mediated excitation combined with diminished GABAergic inhibition promotes central sensitization and maladaptive processing of negative affect.
Receptor dysfunction and expression abnormalities within the endogenous opioid system impair descending pain modulation and limbic circuitry, worsening comorbidity.
Neuropeptides including substance P, corticotropin-releasing factor, and oxytocin dysregulate stress reactivity and reward processing, reinforcing pain-depression interactions.

Cite This Study

Ma et al. (2025) studied this question.

synapsesocial.com/papers/6a9071effdb099d0d8dd86a4 https://doi.org/10.3389/fnmol.2025.1675814

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Implication

Narrative review reveals shared neurochemical dysregulation in chronic pain and depression comorbidity, highlighting targeted neurotransmitter pathways for coordinated therapy.

Neurochemical crossroads: exploring the neurotransmitter network in chronic pain and depression comorbidity

Discussion

Member takes

Implication

Key Points

Cite This Study

Neurochemical crossroads: exploring the neurotransmitter network in chronic pain and depression comorbidity

Discussion

Member takes

Implication

Key Points

Cite This Study

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