A rapid capsaicin-activated current in rat trigeminal ganglion neurons.

Abstract

A subpopulation of pain fibers are activated by capsaicin, the ingredient in red peppers that produces a burning sensation when eaten or placed on skin. Previous studies on dorsal root ganglion neurons indicated that capsaicin activates sensory nerves via a single slowly activating and inactivating inward current. In rat trigeminal neurons, we identified a second capsaicin-activated inward current. This current can be distinguished from the slow one in that it rapidly activates and inactivates, requires Ca2+ for activation, and is insensitive to the potent capsaicin agonist resiniferatoxin. The rapid current, like the slower one, is inhibited by ruthenium red and capsazepine. The two capsaicin-activated inward currents share many similarities with the two inward currents activated by lowering the pH to 6.0. These similarities include kinetics, reversal potentials, responses to Ca2+, and inhibition by ruthenium red and capsazepine. These results suggest that acidic stimuli may be an endogenous activator of capsaicingated currents and therefore may rationalize why pain is produced when the plasma acidity is increased, as occurs during ischemia and inflammation.Capsaicin is eaten daily by over a third of the world's population (1) and produces its pungent taste sensation when it binds to receptors on a subset of nociceptors and warm thermoreceptors (2-8). Upon prolonged application, it blocks nerve fiber conduction and depletes peptides from nerve terminals, which accounts for its clinical use as an analgesic and anti-inflammatory agent (9, 10). Capsaicin is thought to produce these effects by activating a single type of cationselective ion channel present in a subset of nociceptive fibers (3).In the process of investigating the responses of trigeminal ganglion cells to chemical stimuli (11, 12), we found that capsaicin also activates a current with characteristics quite distinct from the one previously described. The two currents activated by capsaicin exhibit many similarities with the two currents activated by acidic stimuli, suggesting that acid may be an endogenous activator of these capsaicin-activated currents. MATERIALS AND METHODSRat trigeminal cells were cultured and whole-cell currents were recorded by conventional culturing (13) Na2HPO4, 5.6 mM D-glucose, and 10 mM Hepes. They were then incubated for 40 min at 37°C in HBSS containing 1 mg of collagenase per ml (type XI-S), triturated with a flamed Pasteur pipette, and finally incubated at 37°C for 6 min with 0

Primary Afferent Stimulation Differentially Potentiates Excitatory and Inhibitory Inputs to Spinal Lamina II Outer and Inner Neurons

“…Therefore the mEPSC amplitude increase by capsaicin is likely caused by activation of VR 1 receptors and TTX-resistant Na ϩ channels present on dorsal root fibers. Additionally, activation of VR 1 receptors produces an inward current carried by nonselective cations with a high permeability for divalent cations such as Ca 2ϩ (Caterina et al 1997;Liu and Simon 1994). It is possible that Ca 2ϩ influx directly through the ionophore of VR 1 receptors may also contribute to the amount of glutamate release from the primary afferents.…”

Differential Activation and Desensitization of Sensory Neurons by Resiniferatoxin

“…Liu and Simon (1994), for example, characterized currents induced in single sensory neurons in response to capsaicin and RTX. At least one subset of currents was inducible by capsaicin but not RTX (at the concentration examined), and furthermore, significant differences were found in the desensitization patterns of the different vanilloid-sensitive currents (Liu and Simon, 1996).…”

Nonselective cation conductance activated by muscarinic and purinergic receptors in rat spiral ganglion neurons

“…Although sharing of the GIRK channel by a large number of neurotransmitters is well known (2,11,40,61,64), activation of a nonselective cation conductance by different ligands on the same cell has been mentioned only in a few reports in neurons (4,22,39,59). The porelike nonselective conductance activated by the marine toxin maitotoxin and P2Z purinergic receptor stimulation by BzATP have also been shown to share a common cytolytic pore in nonneuronal cells (56).…”