Similarities and Differences between the Responses of Rat Sensory Neurons to Noxious Heat and Capsaicin

We have compared the membrane response of rat primary sensory neurons to capsaicin and noxious heat, using electrophysiological and ion flux measurements. Our aim was to determine whether, as recently proposed, the same molecular entity accounts for excitation by both types of stimulus. The properties of the ion channels activated by heat and capsaicin show many similarities but also important differences. The calcium permeability of heat-activated channels is lower than that of capsaicin-activated channels. Distinct single channels respond to heat or capsaicin, and only a few show dual sensitivity. At the whole-cell level, individual cells invariably show dual sensitivity, but the amplitudes of the responses show little correlation. We conclude that distinct molecular entities, which are both likely to be derived from the VR1 gene product, account for the membrane responses to heat and capsaicin.

[1]  R. Orkand,et al.  Temperature coefficient of membrane currents induced by noxious heat in sensory neurones in the rat , 1999, The Journal of physiology.

[2]  D. Julius,et al.  A capsaicin-receptor homologue with a high threshold for noxious heat , 1999, Nature.

[3]  G. Michael,et al.  Differential Expression of the mRNA for the Vanilloid Receptor Subtype 1 in Cells of the Adult Rat Dorsal Root and Nodose Ganglia and Its Downregulation by Axotomy , 1999, The Journal of Neuroscience.

[4]  I. Nagy,et al.  Noxious heat activates all capsaicin-sensitive and also a sub-population of capsaicin-insensitive dorsal root ganglion neurons , 1999, Neuroscience.

[5]  A. Basbaum,et al.  The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli , 1998, Neuron.

[6]  D. Julius,et al.  The capsaicin receptor: a heat-activated ion channel in the pain pathway , 1997, Nature.

[7]  R. Treede,et al.  Coexpression of heat-evoked and capsaicin-evoked inward currents in acutely dissociated rat dorsal root ganglion neurons , 1997, Neuroscience Letters.

[8]  J. Levine,et al.  Heat transduction in rat sensory neurons by calcium-dependent activation of a cation channel. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[9]  D. A. Brown,et al.  A swelling‐activated chloride current in rat sympathetic neurones , 1997, The Journal of physiology.

[10]  P. Cesare,et al.  A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[11]  S. Chunga,et al.  Changes in the kinetics and conductance of N-methyl-d-aspartate (NMDA)receptor activated single channels with temperature , 1995, Neuroscience Letters.

[12]  S. Bevan,et al.  A comparison of capsazepine and ruthenium red as capsaicin antagonists in the rat isolated urinary bladder and vas deferens , 1993, British journal of pharmacology.

[13]  H P Rang,et al.  Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin , 1992, British journal of pharmacology.

[14]  S. Bevan,et al.  Sensory neuron-specific actions of capsaicin: mechanisms and applications. , 1990, Trends in pharmacological sciences.

[15]  Peter M. Blumberg,et al.  Specific binding of resiniferatoxin, an ultrapotent capsaicin analog, by dorsal root anglion membranes , 1990, Brain Research.

[16]  A. Dray,et al.  Ruthenium red blocks the capsaicin-induced increase in intracellular calcium and activation of membrane currents in sensory neurones as well as the activation of peripheral nociceptors in vitro , 1990, Neuroscience Letters.

[17]  S. Bevan,et al.  Capsaicin-induced ion fluxes in dorsal root ganglion cells in culture , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  R. Lindsay,et al.  Nerve growth factors (NGF, BDNF) enhance axonal regeneration but are not required for survival of adult sensory neurons , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  H. Handwerker,et al.  Selective excitation by capsaicin of mechano-heat sensitive nociceptors in rat skin , 1988, Brain Research.

[20]  Fred J. Sigworth,et al.  Fitting and Statistical Analysis of Single-Channel Records , 1983 .

[21]  C A Lewis,et al.  Ion‐concentration dependence of the reversal potential and the single channel conductance of ion channels at the frog neuromuscular junction. , 1979, The Journal of physiology.

[22]  R. Keynes The ionic channels in excitable membranes. , 1975, Ciba Foundation symposium.