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Optogenetic and chemogenetic strategies for sustained inhibition of pain

Shrivats M Iyer1, Sam Vesuna1, Charu Ramakrishnan1

  • 1Bioengineering, Stanford University, Stanford, CA 94305, USA.

Scientific Reports
|August 4, 2016
PubMed

Insights

New optogenetic and chemogenetic methods offer sustained pain inhibition. These strategies reduce light exposure and enable non-invasive pain assessment, transforming pain management.

Area of Science:

  • Neuroscience
  • Pain Management
  • Optogenetics
  • Chemogenetics

Background:

  • Sustained inhibition of nociceptors is crucial for pain management.
  • Previous optogenetic methods required constant illumination, limiting clinical application.
  • Peripheral chemogenetic approaches have not demonstrated pain inhibition.

Purpose of the Study:

  • To develop novel strategies for sustained, spatially targeted, and genetically-specific inhibition of nociceptors.
  • To overcome limitations of existing optogenetic and chemogenetic pain control methods.
  • To establish a platform for non-invasive pain sensitivity assessment.

Main Methods:

  • Utilized the step-function inhibitory channelrhodopsin, SwiChR, for sustained optogenetic inhibition.
  • Employed infrequent, transdermally delivered light pulses to reduce light exposure.
  • Demonstrated chemogenetic inhibition using viral expression of the hM4D receptor in nociceptors.
  • Developed optoPAIN, an optogenetic platform for non-invasive pain assessment.

Main Results:

  • SwiChR enabled persistent pain inhibition with >98% reduction in light exposure.
  • Chemogenetic inhibition of mechanical and thermal nociception thresholds was achieved.
  • OptoPAIN successfully assessed pharmacological and chemogenetic inhibition of pain.

Conclusions:

  • Infrequent light stimulation with SwiChR offers a practical approach for long-term optogenetic pain inhibition.
  • Chemogenetics provides a viable method for inhibiting nociception in primary afferent neurons.
  • The optoPAIN platform facilitates non-invasive evaluation of pain modulation strategies.

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