Contribution of μ opioid receptor-expressing dorsal horn interneurons to neuropathic pain-like behavior in mice

Anesthesiology, 2023 · DOI: 10.1097/ALN.0000000000004735 · Published: December 1, 2023

Anesthesiology Neurology Pain Management

Simple Explanation

This study investigates the role of specific spinal cord interneurons that express the mu opioid receptor (MOR) in neuropathic pain in mice. The researchers used genetic tools to identify and manipulate these MOR-expressing interneurons (Oprm1-INs) to observe their impact on pain behaviors after nerve injury. The findings suggest that these interneurons become sensitized after nerve injury and contribute to the development of mechanical and cold hypersensitivity, common symptoms of neuropathic pain.

Study Duration

Not specified

Participants

Mice

Evidence Level

Not specified

Key Findings

1
Spared nerve injury (SNI) reduces Oprm1 gene expression and the responsiveness of Oprm1-INs to DAMGO, a selective μ agonist.
2
SNI sensitizes Oprm1-INs, increasing their intrinsic excitability, spontaneous synaptic activity, and touch-evoked Fos expression.
3
Chemogenetic activation of spinal Oprm1-INs induces mechanical hypersensitivity in uninjured mice, while inhibition reduces neuropathic pain behaviors.

Research Summary

The study characterized the neurochemical and electrophysiological phenotype of Oprm1-INs in the murine dorsal horn, revealing their contribution to neuropathic pain-like behavior. Peripheral nerve injury reduced Oprm1 gene expression and the responsiveness of Oprm1-INs to a selective μ agonist, consistent with the lack of clinical efficacy of opioid analgesics for the treatment of neuropathic pain. Chemogenetic activation of Oprm1-INs produced mechanical allodynia, while chemogenetic inhibition reduced behavioral signs of neuropathic pain, suggesting that Oprm1-INs contribute to mechanical and cold allodynia after nerve injury.

Practical Implications

Novel Therapeutic Targets

Non-opioid strategies to inhibit Oprm1-INs might yield new treatments for neuropathic pain, addressing the limitations of opioid analgesics in neuropathic pain conditions.

Understanding Pain Mechanisms

The study provides insights into the specific neuronal subpopulations and circuits within the dorsal horn that contribute to the processing and transmission of neuropathic pain.

Personalized Pain Management

Future research could focus on differentiating the functions of excitatory vs inhibitory Oprm1-IN subpopulations to develop targeted therapies for different types of neuropathic pain.

Study Limitations

1
The study is limited to a mouse model of spared nerve injury, and findings may not directly translate to human neuropathic pain conditions.
2
The chemogenetic manipulations may have off-target effects or influence other neuronal populations, which could confound the interpretation of results.
3
The study does not fully elucidate the molecular mechanisms underlying the sensitization of Oprm1-INs after nerve injury.

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