0000000000011931
AUTHOR
Wolfgang Greffrath
Inactivation and tachyphylaxis of heat-evoked inward currents in nociceptive primary sensory neurones of rats.
In contrast to other sensory modalities, pain does not decrease when a noxious stimulus is applied at constant intensity (Greene & Hardy, 1962). From this lack of adaptation on the perceptive level it has traditionally been implied that primary nociceptive afferents also do not adapt upon constant stimulation. This is in contrast to the results of recordings from these afferents, which exhibit pronounced adaptation for physical as well as chemical stimuli (Meyer et al. 1994). Peripheral adaptation of nociceptive nerve endings is compensated by central summation (Mendell & Wall, 1965; Price et al. 1977); this slow summation process of small fibre input to the dorsal horn of the spinal cord i…
Changes in cytosolic calcium in response to noxious heat and their relationship to vanilloid receptors in rat dorsal root ganglion neurons.
Heat transduction mechanisms in primary nociceptive afferents have been suggested to involve a vanilloid receptor channel with high calcium permeability. To characterize the changes in free cytosolic calcium evoked by noxious heat stimuli (< or =51 degrees C, 10s), we performed microfluorometric measurements in acutely dissociated small dorsal root ganglion neurons (< or =32.5 microm) of adult rats using the dye FURA-2. Only neurons that responded with a reversible increase in intracellular calcium to high potassium were evaluated. Heat-induced calcium transients (exceeding mean + 3S.D. of the temperature dependence of the dye) were found in 66 of 105 neurons. These transients increased non…
Neural correlates of antinociception in borderline personality disorder.
Context A characteristic feature of borderline personality disorder (BPD) is self-injurious behavior in conjunction with stress-induced reduction of pain perception. Reduced pain sensitivity has been experimentally confirmed in patients with BPD, but the neural correlates of antinociceptive mechanisms in BPD are unknown. We predicted that heat stimuli in patients with BPD would activate brain areas concerned with cognitive and emotional evaluation of pain. Objective To assess the psychophysical properties and neural correlates of altered pain processing in patients with BPD. Design Case-control study. Setting A university hospital. Participants Twelve women with BPD and self-injurious behav…
Co-expression of heat sensitive vanilloid receptor subtypes in rat dorsal root ganglion neurons
Expression of the heat sensitive cation channels TRPV1 and TRPV2 was investigated by immunofluorescence in rat dorsal root ganglion (DRG) neurons. TRPV1-positive neurons were more frequent and had smaller diameters than TRPV2-positive neurons (35.7% vs 7.3%; 22.3 microm vs 27.6 microm), but size distributions overlapped and significant co-expression was seen in 20.7% of TRPV2-positive neurons (1.7% of all). Expression patterns did not differ between tissue sections typically used in immunocytochemistry and dissociated DRG neurons typically used in electrophysiology. Rectangular temperature pulses revealed two patterns of heat-evoked inward currents in small DRG neurons: low-threshold rapidl…
Inward currents in primary nociceptive neurons of the rat and pain sensations in humans elicited by infrared diode laser pulses
Radiant heat is often used to study nociception in vivo. We now used infrared radiation generated by a diode laser stimulator (wavelength 980 nm) to investigate transduction mechanisms for noxious heat stimuli in acutely dissociated dorsal root ganglion (DRG) neurons of rats in vitro. The laser stimulator offered the unique opportunity to test whether the same stimuli also elicit pain sensations in humans. A specific heat-induced current (I(heat)) was elicited in six of 13 small DRG neurons (diameteror =30 microm) tested in the whole-cell configuration of the patch-clamp mode. Current responses in the seven heat-insensitive neurons were within the range explainable by the temperature depend…
Subthreshold oscillation of the membrane potential in magnocellular neurones of the rat supraoptic nucleus
The hypothalamic supraoptic nucleus (SON) contains two major populations of magnocellular neurosecretory neurones, producing and secreting vasopressin and oxytocin, respectively (for review see Poulain & Wakerley 1982). Neurones of a subpopulation of supraoptic neurosecretory cells share the capability of generating phasic bursts of action potentials. In these neurones, action potentials are succeeded by a depolarizing afterpotential (DAP; Andrew, 1987; Armstrong et al. 1994; Li et al. 1995). Depending on the discharge frequency, DAPs summate, eventually resulting in the generation of a plateau potential that gives rise to the discharge of a long-lasting train of action potentials. Thus, DA…
Heat-induced action potential discharges in nociceptive primary sensory neurons of rats.
Although several transducer molecules for noxious stimuli have been identified, little is known about the transformation of the resulting generator currents into action potentials (APs). Therefore we investigated the transformation process for stepped noxious heat stimuli (42-47 degrees C, 3-s duration) into membrane potential changes and subsequent AP discharges using the somata of acutely dissociated small dorsal root ganglion (DRG) neurons (diameteror=32.5 microm) of adult rats as a model for their own peripheral terminals. Three types of heat-induced membrane potential changes were differentiated: type 1, heat-induced AP discharges (approximately 37% of the neurons); type 2, heat-induce…
Capsaicin differentially modulates voltage-activated calcium channel currents in dorsal root ganglion neurones of rats
It is discussed whether capsaicin, an agonist of the pain mediating TRPV1 receptor, decreases or increases voltage-activated calcium channel (VACC) currents (ICa(V)). ICa(V) were isolated in cultured dorsal root ganglion (DRG) neurones of rats using the whole cell patch clamp method and Ba 2+ as charge carrier. In large diameter neurones (>35Am), a concentration of 50AM was needed to reduce ICa(V) (activated by depolarizations to 0 mV) by 80%, while in small diameter neurones (30Am), the IC50 was 0.36 AM. This effect was concentration dependent with a threshold below 0.025 AM and maximal blockade (>80%) at 5AM. The current–voltage relation was shifted to the hyperpolarized direction with an…
Components of after-hyperpolarization in magnocellular neurones of the rat supraoptic nucleusin vitro
1. The pharmacological sensitivity of hyperpolarizing components of spike train after-potentials was examined in sixty-one magnocellular neurones of the rat supraoptic nucleus using intracellular recording techniques in a brain slice preparation. 2. In 26 % of all neurones a slow after-hyperpolarization (AHP) was observed in addition to a fast AHP. In 31 % of all neurones a depolarizing after-potential (DAP) was observed. 3. The fast AHP was blocked by apamin whereas the slow AHP was blocked by charybdotoxin (ChTX). The DAP was enhanced by ChTX or a DAP was unmasked if not present during the control period. 4. Low concentrations of TEA (0.15-1.5 mM) induced effects on the slow AHP and the D…
Phosphorylation of extracellular signal-related protein kinase is required for rapid facilitation of heat-induced currents in rat dorsal root ganglion neurons
A subgroup of dorsal root ganglion (DRG) neurons responds to noxious heat with an influx of cations carried by specific ion channels such as the transient receptor potential channel of the vanilloid receptor type, subtype 1 (TRPV1). Application of capsaicin induces a reversible facilitation of these currents. This facilitation could be an interaction of two agonists at their common receptor or be caused by an influx of calcium ions into the cell. Calcium influx into the cell can activate protein kinases such as the extracellular signal-related protein kinase (ERK) pathway. This study explored the kinetics, calcium-dependency and intracellular signals following application of capsaicin and l…
Differential nociceptive deficits in patients with borderline personality disorder and self-injurious behavior: laser-evoked potentials, spatial discrimination of noxious stimuli, and pain ratings.
Approximately 70-80% of women meeting criteria for borderline personality disorder (BPD) report attenuated pain perception or analgesia during non-suicidal, intentional self-mutilation. The aim of this study was to use laser-evoked potentials (LEPs) and psychophysical methods to differentiate the factors that may underlie this analgesic state. Ten unmedicated female patients with BPD (according to DSM-IV) and 14 healthy female control subjects were investigated using brief radiant heat pulses generated by a thulium laser and five-channel LEP recording. Heat pulses were applied as part of a spatial discrimination task (two levels of difficulty) and during a mental arithmetic task. BPD patien…
Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the cannabinoid receptor CB1 in rat dorsal root ganglion neurons.
Potassium channels contribute to basic neuronal excitability and modulation. Here, we examined expression patterns of the voltage-gated potassium channel Kv1.4, the nociceptive transduction channels TRPV1 and TRPV2 as well as the putative anti-nociceptive cannabinoid receptor CB1 by immunofluorescence double-labelings in sections of rat dorsal root ganglia (DRGs). Kv1.4, TRPV1 and CB1 were each detected in about one third of neurons (35.7+/-0.5%, 29.4+/-1.1% and 36.4+/-0.5%, respectively, mean diameter 19.1+/-0.3 microm). TRPV2 was present in 4.4+/-0.4% of all neurons that were significantly larger in diameter (27.4+/-0.7 microm; P < 0.001). Antibody double-labeling revealed that the majori…
Acetylsalicylic acid reduces heat responses in rat nociceptive primary sensory neurons – evidence for a new mechanism of action
Acetylsalicylic acid (ASA) is thought to exert its peripheral analgesic effects via inhibition of cyclooxygenase. We now studied the effects of ASA on heat responses in primary nociceptive neurons by whole-cell patch-clamp and calcium microfluorimetry experiments. Heat-evoked inward currents in acutely dissociated rat dorsal root ganglion neurons were significantly reduced by ASA in a dose-dependent and reversible manner (IC(50) 375 nM, Hill slope -2.2, maximum effect 55%). Heat-evoked calcium transients (measured with FURA-2) were reversibly reduced by 53+/-14% (P0.05) by co-application of 1 microM ASA. The low IC(50) value, the rapid occurrence, and the reversibility of the observed effec…
'TRPing' synaptic ribbon function in the rat pineal gland: neuroendocrine regulation involves the capsaicin receptor TRPV1.
Synaptic ribbons (SRs) are presynaptic structures thought to regulate and facilitate multivesicular release. In the pineal gland, they display a circadian rhythm with higher levels at night paralleling melatonin synthesis. To gain more insight into the processes involved and the possible functions of these structures, a series of experiments were conducted in rodents. We studied the regional distribution of a molecular marker of pineal SRs, the kinesin motor KIF3A in the gland. Respective immunoreactivity was abundant in central regions of the gland where sympathetic fibers were less dense, and vice versa, revealing that intercellular communication between adjacent pinealocytes is enhanced …
Inhibition of rapid heat responses in nociceptive primary sensory neurons of rats by vanilloid receptor antagonists.
Recent studies demonstrated that heat-sensitive nociceptive primary sensory neurons respond to the vanilloid receptor (VR) agonist capsaicin, and the first cloned VR is a heat-sensitive ion channel. Therefore we studied to what extent heat-evoked currents in nociceptive dorsal root ganglion (DRG) neurons can be attributed to the activation of native vanilloid receptors. Heat-evoked currents were investigated in 89 neurons acutely dissociated from adult rat DRGs as models for their own terminals using the whole cell patch-clamp technique. Locally applied heated extracellular solution (effective temperature ∼53°C) rapidly activated reversible and reproducible inward currents in 80% (62/80) o…
Effects of Anandamide and Noxious Heat on Intracellular Calcium Concentration in Nociceptive DRG Neurons of Rats
As an endogenous agonist at the cannabinoid receptor CB1 and the capsaicin-receptor TRPV1, anandamide may exert both anti- and pronociceptive actions. Therefore we studied the effects of anandamide and other activators of both receptors on changes in free cytosolic calcium ([Ca2+]i) in acutely dissociated small dorsal root ganglion neurons (diameter: ≤30 μm). Anandamide (10 μM) increased [Ca2+]iin 76% of the neurons. The EC50was 7.41 μM, the Hill slope was 2.15 ± 0.43 (mean ± SE). This increase was blocked by the competitive TRPV1-antagonist capsazepine (10 μM) and in Ca2+-free extracellular solution. Neither exclusion of voltage-gated sodium channels nor additional blockade of voltage-gate…