Peripherally driven low-threshold inhibitory inputs to lamina I local-circuit and projection neurones: a new circuit for gating pain responses

J Physiol. 2014 Apr 1;592(7):1519-34. doi: 10.1113/jphysiol.2013.269472. Epub 2014 Jan 13.

Abstract

Spinal lamina I is a key element of the pain processing system which relays primary afferent input to supraspinal areas. However, little is known about how the signal is modulated by its intrinsic network including local-circuit neurones (LCNs) and much less numerous anterolateral tract projection neurones (PNs). Here, we used whole-cell patch clamp recordings in an isolated spinal cord preparation to examine properties of identified LCNs (n = 85) and PNs (n = 73) in their functionally preserved local networks. Forty LCNs showed spontaneous rhythmic firing (2-7 Hz) at zero current injection, which persisted in the presence of blockers of fast synaptic transmission. In the remaining cases, most LCNs and PNs fired tonically in response to depolarizing current injections. We identified LCNs and PNs receiving low-threshold primary afferent-driven inhibitory inputs, which in many cases were disynaptic and temporally preceded classical high-threshold excitatory inputs. This direct inhibitory link between low-threshold afferents and PNs can function as a postsynaptic gate controlling the nociceptive information flow in the spinal cord. The LCNs were found to be integrated into the superficial dorsal horn network by their receipt of monosynaptic and disynaptic inputs from other lamina I and II neurones. One-third of LCNs and two-thirds of PNs tested responded to substance P application. Thus, substance P released by a noxious afferent stimulation may excite PNs in two ways: directly, and via the activation of presynaptic LCN circuitries. In conclusion, we have described important properties of identified lamina I neurones and their roles in a new circuit for gating pain responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials
  • Glycine / metabolism
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials
  • Neural Inhibition* / drug effects
  • Neural Pathways / physiopathology
  • Pain / metabolism
  • Pain / physiopathology*
  • Pain Perception*
  • Periodicity
  • Rats, Wistar
  • Reaction Time
  • Signal Transduction* / drug effects
  • Spinal Cord Dorsal Horn / drug effects
  • Spinal Cord Dorsal Horn / metabolism
  • Spinal Cord Dorsal Horn / physiopathology*
  • Substance P / pharmacology
  • Synaptic Transmission
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Substance P
  • gamma-Aminobutyric Acid
  • Glycine