Feedback mechanisms in the regulation of intracellular calcium ([Ca2+]i) in the peripheral nociceptive system: Role of TRPV-1 and pain related receptors

T. Hagenacker, D. Ledwig, D. Büsselberg

Research output: Contribution to journalReview article

23 Citations (Scopus)


Multimodal stimuli like heat, cold, bacterial or mechanical events are able to elicit pain, which is necessary to guarantee survival. However, the control of pain is of major clinical importance. The perception and transduction of pain is differentially modulated in the peripheral and central nervous system (CNS): while peripheral structures modulate these signals, the perception of pain occurs in the CNS. In recent years major advances have been made in the understanding of the processes which are involved in pain sensation. For the peripheral pain reception, the importance of specific pain receptors of the transition receptor pore (TRP)-family (e.g. the TRPV-1 receptor) has been analyzed. These receptors/channels are localized at the cell membrane of nociceptive neurones as well as in membranes of intracellular calcium stores like the endoplasmic reticulum. While the associated channel conducts different ions, a major proportion is calcium. Therefore, this review focuses on (1) the modulations of intracellular calcium ([Ca2+]i) initiated by the activation of pain receptors and (2) the consequences of [Ca2+]i changes for the processing of pain signals at the peripheral side. The possible interference of TRPV-1 induced [Ca2+]i modulations to the function of other membrane receptors and channels, like voltage gated calcium, sodium or potassium channels, or co-expressed CB1-receptors will be discussed. The latter interactions are of specific interest since the analgetic properties of endo- and exo-cannabinoids are mediated by CB1 receptors and their activation significantly modulates the calcium induced release of pain related transmitters. Furthermore, multiple cross links between different pain modulating intracellular pathways and their dependence on [Ca2+]i modulations will be illuminated. Overall, this review will summarize new insights resulting in the understanding of the prominent influence of [Ca2+]i for processes which are involved in pain sensation.

Original languageEnglish
Pages (from-to)215-227
Number of pages13
JournalCell calcium
Issue number3
Publication statusPublished - Mar 2008



  • Bradykinin receptors
  • Calcium stores
  • Cannabinoid-receptors
  • Intracellular calcium
  • Nociception
  • Opioid-receptors
  • Pain
  • TRPV-receptors

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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