Peripheral Sensory Neurons Expressing Melanopsin Respond to Light

Front Neural Circuits. 2016 Aug 10;10:60. doi: 10.3389/fncir.2016.00060. eCollection 2016.

Abstract

The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior.

Keywords: choroid; cornea; ipRGC; migraine; optic nerve injury; sensory ganglion.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Disease Models, Animal
  • Female
  • Humans
  • Light*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Migraine Disorders / metabolism
  • Migraine Disorders / physiopathology*
  • Optic Nerve Injuries / metabolism
  • Optic Nerve Injuries / physiopathology*
  • Retinal Ganglion Cells / physiology*
  • Rod Opsins / metabolism
  • Rod Opsins / physiology*
  • Trigeminal Ganglion / metabolism
  • Trigeminal Ganglion / physiology*

Substances

  • Rod Opsins
  • melanopsin