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Kappa Opioid Receptor Distribution and Function in Primary Afferents
Lindsey M Snyder1, Michael C Chiang1, Emanuel Loeza-Alcocer1
1Department of Neurobiology and the Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Neuron
|September 22, 2018
Summary
Kappa opioid receptor (KOR) is expressed in sensory neurons, inhibiting pain signaling. Peripherally acting KOR agonists effectively reduce pain and itch, offering a new therapeutic approach.
Area of Science:
- Neuroscience
- Pain Research
- Pharmacology
Background:
- Kappa opioid receptor (KOR) signaling is known to inhibit primary afferents.
- The specific somatosensory neuron populations expressing KOR have not been fully elucidated.
Purpose of the Study:
- To identify the specific somatosensory neuron types expressing KOR.
- To investigate the functional roles of KOR in both central and peripheral pain pathways.
- To evaluate the therapeutic potential of peripherally restricted KOR agonists.
Main Methods:
- Utilized a novel KOR-cre knockin mouse model.
- Employed viral tracing, single-cell RT-PCR, and ex vivo electrophysiological recordings.
- Assessed behavioral responses to pain and itch in preclinical models.
Main Results:
- KOR expression was confirmed in peptidergic sensory neurons and low-threshold mechanoreceptors.
- Central KOR signaling inhibits neurotransmission from KOR-expressing afferents.
- Peripheral KOR activation suppresses neurogenic inflammation and nociceptor sensitization.
- Peripherally restricted KOR agonists reduced pain, itch, and hypersensitivity in a surgical incision model.
Conclusions:
- KOR is expressed in key somatosensory neuron populations involved in pain transmission.
- KOR signaling modulates pain perception both centrally and peripherally.
- Peripherally restricted KOR agonists represent a promising therapeutic strategy for managing pain and itch.
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