Altered intrinsic and synaptic properties of lumbosacral dorsal horn neurons in a mouse model of colitis

Neuroscience. 2017 Oct 24:362:152-167. doi: 10.1016/j.neuroscience.2017.08.029. Epub 2017 Aug 23.

Abstract

Visceral pain in inflammatory and functional gastrointestinal conditions is a major clinical problem. The exact mechanisms underlying the development of pain, during and after visceral inflammation are unknown. However, clinical and pre-clinical evidence suggests plasticity within the spinal cord dorsal horn is a contributing factor. Here we use an in vivo preparation and patch-clamp electrophysiology to test whether the synaptic and intrinsic properties of superficial dorsal horn (SDH) neurons are altered 5days after the induction of mild colitis in adult male mice (i.e. during acute inflammation of the colon). Whole-cell recordings were made from lumbosacral (L6-S1) superficial dorsal horn neurons (SDH), in animals under isoflurane anesthesia. Noxious colorectal distension (CRD) was used to identify SDH neurons with colonic inputs, while stimulation of the hind paw and tail was employed to assess convergent cutaneous input. Following inflammation, a significantly increased proportion of SDH neurons received both colonic and cutaneous inputs, compared to neurons in naïve animals. In addition, the nature and magnitude of responses to CRD and cutaneous stimulation differed in inflamed animals, as was spontaneous excitatory synaptic drive. Conversely, several measures of intrinsic excitability were altered in a manner that would decrease SDH network excitability following colitis. We propose that during inflammation, sensitization of colonic afferents results in increased signaling to the SDH. This is accompanied by plasticity in SDH neurons whereby their intrinsic properties are changed to compensate for altered afferent activity.

Keywords: in vivo; spinal cord; visceral inflammation.

MeSH terms

  • Action Potentials
  • Acute Disease
  • Animals
  • Colitis / pathology
  • Colitis / physiopathology*
  • Colon / physiopathology
  • Disease Models, Animal
  • Excitatory Postsynaptic Potentials
  • Lumbar Vertebrae
  • Male
  • Mice, Inbred C57BL
  • Patch-Clamp Techniques
  • Physical Stimulation
  • Posterior Horn Cells / physiology*
  • Rectum / physiopathology
  • Sacrum
  • Skin / physiopathology
  • Trinitrobenzenesulfonic Acid
  • Visceral Pain / physiopathology

Substances

  • Trinitrobenzenesulfonic Acid