Relationship between electrophysiological signature and defined sensory modality of trigeminal ganglion neurons in vivo

2013 ◽  
Vol 109 (3) ◽  
pp. 749-757 ◽  
Author(s):  
M. Danilo Boada
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Sensory Modality ◽  
High Threshold ◽  
Sensory Afferents ◽  
Receptor Field ◽  
Nociceptive Neurons ◽  
Mechanical Threshold ◽  
Ganglion Neurons

The trigeminal ganglia (TG) innervate a heterogeneous set of highly sensitive and exposed tissues. Weak, innocuous stimuli can evoke pain as a normal response in some areas such as the cornea. This observation implies, however, the capability of low-threshold mechanoreceptors, inducing pain in the normal condition. To clarify this matter, the present study correlates the electrical signature (both fiber conduction velocity and somatic electrical properties) with receptor field, mechanical threshold, and temperature responsiveness of sensory afferents innervating tissues with dissimilar sensitivity (skin vs. cornea) in the trigeminal domain. Intracellular recordings were obtained in vivo from 148 neurons of the left TG of 62 mice. In 111 of these neurons, the peripheral receptor field was successfully localized: 96 of them innervated the hairy skin, while the remaining 15 innervated the cornea. The electrical signature was defined and peripheral responses correlated with tissue target. No high threshold neurons were found in the cornea. Moreover, the electrical signature of corneal afferents resembles nociceptive neurons in the skin. TG skin afferents showed similar membrane electrical signature and sensory modality as skin afferents from dorsal root ganglion, although TG afferents exhibited a shorter duration of afterhyperpolarization then those previously described in dorsal root ganglion. These data suggest than new or different ways to classify and study TG sensory neurons may be required.

scholarly journals In vivo characterization of distinct modality-specific subsets of somatosensory neurons using GCaMP

2016 ◽  
Vol 2 (11) ◽  
pp. e1600990 ◽  
Author(s):  
Edward C. Emery ◽  
Ana P. Luiz ◽  
Shafaq Sikandar ◽  
Rán Magnúsdóttir ◽  
Xinzhong Dong ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Transgenic Mice ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Rational Approach ◽  
Prostaglandin E ◽  
Nociceptive Neurons ◽  
Ganglion Neurons

Mechanistic insights into pain pathways are essential for a rational approach to treating this vast and increasing clinical problem. Sensory neurons that respond to tissue damage (nociceptors) may evoke pain sensations and are typically classified on the basis of action potential velocity. Electrophysiological studies have suggested that most of the C-fiber nociceptors are polymodal, responding to a variety of insults. In contrast, gene deletion studies in the sensory neurons of transgenic mice have frequently resulted in modality-specific deficits. We have used an in vivo imaging approach using the genetically encoded fluorescent calcium indicator GCaMP to study the activity of dorsal root ganglion sensory neurons in live animals challenged with painful stimuli. Using this approach, we can visualize spatially distinct neuronal responses and find that >85% of responsive dorsal root ganglion neurons are modality-specific, responding to either noxious mechanical, cold, or heat stimuli. These observations are mirrored in behavioral studies of transgenic mice. For example, deleting sodium channel Nav1.8 silences mechanical- but not heat-sensing sensory neurons, consistent with behavioral deficits. In contrast, primary cultures of axotomized sensory neurons show high levels of polymodality. After intraplantar treatment with prostaglandin E2, neurons in vivo respond more intensely to noxious thermal and mechanical stimuli, and additional neurons (silent nociceptors) are unmasked. Together, these studies define polymodality as an infrequent feature of nociceptive neurons in normal animals.

scholarly journals Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0192760
Author(s):  
Jason A. Bleedorn ◽  
Troy A. Hornberger ◽  
Craig A. Goodman ◽  
Zhengling Hao ◽  
Susannah J. Sample ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Signaling Events ◽  
Bone Loading ◽  
Ganglion Neurons

Interaction of opioids and membrane potential to modulate Ca2+ channels in rat dorsal root ganglion neurons

1995 ◽  
Vol 73 (5) ◽  
pp. 1793-1798 ◽  
Author(s):  
M. D. Womack ◽  
E. W. McCleskey
Keyword(s):  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Action Potentials ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
High Threshold ◽  
Partial Recovery ◽  
Drg Neurons ◽  
Ganglion Neurons ◽  
Ca2 Channels

1. Using patch-clamp methods, we show that brief prepulses to very positive voltages increase (facilitate) the amplitude of current through Ca2+ channels during a subsequent test pulse in some, but not all, dorsal root ganglion (DRG) sensory neurons. The amplitude of this facilitated current generally increases when the Ca2+ channels are inhibited by activation of the mu-opioid receptor. 2. The facilitated current is blocked by omega-conotoxin GVIA, activates in the range of high-threshold Ca2+ channels, and inactivates at relatively negative holding voltages. Thus facilitated current passes through N-type Ca2+ channels, the same channels that are inhibited by opioids and control neurotransmitter release in sensory neurons. 3. Although maximal facilitation occurs only at unphysiologically high membrane potentials (above +100 mV), some facilitation is seen after prepulses to voltages reached during action potentials. After return to the holding potential, facilitation persists for hundreds of milliseconds, considerably longer than in other neurons. Brief trains of pulses designed to mimic action potentials caused small facilitation (19% of maximal) in a fraction (8 of 24) of opioid-inhibited neurons. 4. We conclude that 1) prepulses to extremely positive voltages can cause partial recovery of Ca2+ channels inhibited by opioids; and 2) small, but detectable, facilitation is also seen after physiological stimulation in some DRG neurons. Facilitation, largely considered a biophysical epiphenomenon because of the extreme voltages used to induce it, appears to be physiologically relevant during opioid inhibition of Ca2+ channels in DRG neurons.

Similar Electrophysiological Changes in Axotomized and Neighboring Intact Dorsal Root Ganglion Neurons

2003 ◽  
Vol 89 (3) ◽  
pp. 1588-1602 ◽  
Author(s):  
Chao Ma ◽  
Yousheng Shu ◽  
Zheng Zheng ◽  
Yong Chen ◽  
Hang Yao ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Receptive Fields ◽  
Input Resistance ◽  
Spinal Nerve ◽  
Dorsal Root Ganglion Neurons ◽  
Drg Neurons ◽  
Ganglion Neurons

We investigated electrophysiological changes in chronically axotomized and neighboring intact dorsal root ganglion (DRG) neurons in rats after either a peripheral axotomy consisting of an L5 spinal nerve ligation (SNL) or a central axotomy produced by an L5 partial rhizotomy (PR). SNL produced lasting hyperalgesia to punctate indentation and tactile allodynia to innocuous stroking of the foot ipsilateral to the injury. PR produced ipsilateral hyperalgesia without allodynia with recovery by day 10. Intracellular recordings were obtained in vivo from the cell bodies (somata) of axotomized and intact DRG neurons, some with functionally identified peripheral receptive fields. PR produced only minor electrophysiological changes in both axotomized and intact somata in L5 DRG. In contrast, extensive changes were observed after SNL in large- and medium-sized, but not small-sized, somata of intact (L4) as well as axotomized (L5) DRG neurons. These changes included (in relation to sham values) higher input resistance, lower current and voltage thresholds, and action potentials with longer durations and slower rising and falling rates. The incidence of spontaneous activity, recorded extracellularly from dorsal root fibers in vitro, was significantly higher (in relation to sham) after SNL but not after PR, and occurred in myelinated but not unmyelinated fibers from both L4 (9.1%) and L5 (16.7%) DRGs. We hypothesize that the changes in the electrophysiological properties of axotomized and intact DRG neurons after SNL are produced by a mechanism associated with Wallerian degeneration and that the hyperexcitability of intact neurons may contribute to SNL-induced hyperalgesia and allodynia.

scholarly journals Intra-articular AAV-PHP.S mediated chemogenetic targeting of knee-innervating dorsal root ganglion neurons alleviates inflammatory pain in mice

2020 ◽  
Author(s):  
Sampurna Chakrabarti ◽  
Luke A. Pattison ◽  
Balint Doleschall ◽  
Rebecca H. Rickman ◽  
Helen Blake ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Knee Joint ◽  
Joint Pain ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Drg Neurons ◽  
Neuron Excitability ◽  
Ganglion Neurons

AbstractObjectiveJoint pain is the major clinical symptom of arthritis that affects millions of people. Controlling the excitability of knee-innervating dorsal root ganglion (DRG) neurons (knee neurons) could potentially provide pain relief. Therefore, our objective was to evaluate whether the newly engineered adeno-associated virus (AAV) serotype, AAV-PHP.S, can deliver functional artificial receptors to control knee neuron excitability following intra-articular knee injection.MethodsAAV-PHP.S virus packaged with dTomato fluorescent protein and either excitatory (Gq) or inhibitory (Gi) designer receptors activated by designer drugs (DREADDs) was injected into the knee joint of adult mice. Labelling of DRG neurons by AAV-PHP.S from the knee was evaluated using immunohistochemistry. Functionality of Gq- and Gi-DREADDs was evaluated using whole-cell patch clamp electrophysiology on acutely cultured DRG neurons. Pain behavior in mice was assessed using a digging assay, dynamic weight bearing and rotarod, before and after intra-peritoneal administration of the DREADD activator, Compound 21.ResultsWe show that AAV-PHP.S can deliver functional genes into the DRG neurons when injected into the knee joint in a similar manner to the well-established retrograde tracer, fast blue. Short-term activation of AAV-PHP.S delivered Gq-DREADD increases excitability of knee neurons in vitro, without inducing overt pain in mice when activated in vivo. By contrast, in vivo Gi-DREADD activation alleviated complete Freund’s adjuvant mediated knee inflammation-induced deficits in digging behavior, with a concomitant decrease in knee neuron excitability observed in vitro.ConclusionsWe describe an AAV-mediated chemogenetic approach to specifically control joint pain, which may be utilized in translational arthritic pain research.

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