Capsaicin-induced neurotoxicity in cultured dorsal root ganglion neurons: involvement of calcium-activated proteases

Neuroscience. 1995 Apr;65(4):1099-108. doi: 10.1016/0306-4522(94)00548-j.


We examined the mechanism by which capsaicin produces its toxic effects on cultures of rat sensory neurons. Capsaicin caused a robust increase in [Ca2+]i in a subpopulation of cultured rat dorsal root ganglion neurons. Similarly, a brief exposure to capsaicin resulted in delayed degeneration of a subpopulation of the cells. This subpopulation (about 35% of the cells present) was characterized by a capsaicin-induced uptake of Co2+, which could be detected cytochemically. Both capsaicin-induced Co2+ uptake and capsaicin-induced cell death were blocked by the capsaicin antagonist Ruthenium Red. Cell death was also prevented by removal of external calcium or by inhibiting calcium-activated proteases such as calpain. Evidence that calpain activity was increased was provided by examining the amount of degradation of the preferred calpain substrate alpha-spectrin. Capsaicin treatment produced a significant increase in the levels of the 150,000 molecular weight spectrin breakdown product. Furthermore, applying the protease inhibitors E64 or MDL 28,170 reduced capsaicin-mediated cell death. It is concluded that capsaicin kills a subpopulation of sensory neurons by activating a receptor-operated channel. The consequent Ca2+ ion influx causes large increases in [Ca2+]i and subsequent activation of Ca(2+)-sensitive proteases. This model provides support for the role of [Ca2+]i as the orchestrator of delayed neuronal degeneration.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Calcium / physiology*
  • Calpain / physiology*
  • Capsaicin / toxicity*
  • Cell Death / drug effects
  • Cells, Cultured
  • Cytophotometry
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Fura-2
  • Ganglia, Spinal / cytology*
  • Ganglia, Spinal / drug effects
  • Histocytochemistry
  • Neurons / drug effects*
  • Neurotoxins / toxicity*
  • Patch-Clamp Techniques
  • Rats


  • Neurotoxins
  • Calpain
  • Capsaicin
  • Calcium
  • Fura-2