Spinothalamic Tract Neurons Research Articles

Presynaptic Enhancement of Transmission from Nociceptors Expressing Nav1.8 onto Lamina-I Spinothalamic Tract Neurons by Spared Nerve Injury in Mice.

Alteration of synaptic function in the dorsal horn (DH) has been implicated as a cellular substrate for the development of neuropathic pain, but certain details remain unclear. In particular, the lack of information on the types of synapses that undergo functional changes hinders the understanding of disease pathogenesis from a synaptic plasticity perspective. Here, we addressed this issue by using optogenetic and retrograde tracing ex vivo to selectively stimulate first-order nociceptors expressing Nav1.8 (NRsNav1.8) and record the responses of spinothalamic tract neurons in spinal lamina I (L1-STTNs). We found that spared nerve injury (SNI) increased excitatory postsynaptic currents (EPSCs) in L1-STTNs evoked by photostimulation of NRsNav1.8 (referred to as Nav1.8-STTN EPSCs). This effect was accompanied by a significant change in the failure rate and paired-pulse ratio of synaptic transmission from NRsNav1.8 to L1-STTN and in the frequency (not amplitude) of spontaneous EPSCs recorded in L1-STTNs. However, no change was observed in the ratio of AMPA to NMDA receptor-mediated components of Nav1.8-STTN EPSCs or in the amplitude of unitary EPSCs constituting Nav1.8-STTN EPSCs recorded with extracellular Ca2+ replaced by Sr2+ In addition, there was a small increase (approximately 10%) in the number of L1-STTNs showing immunoreactivity for phosphorylated extracellular signal-regulated kinases in mice after SNI compared with sham. Similarly, only a small percentage of L1-STTNs showed a lower action potential threshold after SNI. In conclusion, our results show that SNI induces presynaptic modulation at NRNav1.8 (consisting of both peptidergic and nonpeptidergic nociceptors) synapses on L1-STTNs forming the lateral spinothalamic tract.

The Role of Mediodorsal Thalamic Projections to Prelimbic Medial Prefrontal Cortex in Affective Pain Processing and Pain Tolerance

Both human and rodent studies demonstrate that the mediodorsal (MD) thalamus, a target of spinothalamic tract neurons, is involved in processing the affective component of pain. The specific role of MD nuclei and their projections in pain remains incompletely understood. MD projects to several cortical regions, one of which is the prelimbic region of the prefrontal cortex (PL), an area thought to play a role in pain processing and modulation. The purpose of this study was to elucidate the role of MD neurons that project to the PL in affective pain processing and pain tolerance. We utilized viral vectors and the Cre-lox system to specifically express designer receptors exclusively activated by designer drugs (DREADDs) in MD pyramidal neurons that project to the PL to activate or deactivate the circuit with CNO. Mice received chronic constriction injuries (CCI) contralateral to viral injections. This was followed by conditioned place aversion (CPA) or preference tests and the operant plantar thermal assay (OPTA). Activating the unilateral MD-PL circuit using excitatory DREADDs in naïve mice did not produce a conditioned place aversion. It did, however, produce place aversion in mice with CCI. Unilaterally inhibiting the MD-PL circuit in mice with CCI did not produce a place preference. There was no difference in the time spent tolerating a noxious temperature to receive a sucrose reward when this circuit was either activated or inhibited in mice with CCI. The MD-PL circuit is involved in the enhancement of aversion in mice with chronic pain. This circuit, however, is not sufficient to produce aversion in pain-free mice. This circuit may not be necessary for the affective component of pain, as unilaterally inhibiting it did not result in preference in mice with CCI. Finally, this circuit may not be involved with the modulation of pain tolerance in mice with CCI. Grant support from R01 NS107356.

Impaired Autophagy of GABAergic Interneurons in Neuropathic Pain.

Neuropathic pain (NP) is caused by lesions of the peripheral fibers and central neurons in the somatosensory nervous system and affects 7–10% of the general population. Although the distinct cause of neuropathic pain has been investigated in primary afferent neurons over the years, pain modulation by central sensitization remains controversial. NP is believed to be driven by cell type-specific spinal synaptic plasticity in the dorsal horn. Upon intense afferent stimulation, spinothalamic tract neurons are potentiated, whereas GABAergic interneurons are inhibited leading to long-term depression. Growing evidences suggest that the inhibition of GABAergic neurons plays pivotal roles in the manifestation of neuropathic and inflammatory pain states. Downregulation of GABA transmission and impairment of GABAergic interneurons in the dorsal horn are critical consequences after spinal cord and peripheral nerve injuries. These impairments in GABAergic interneurons may be associated with dysfunctional autophagy, resulting in neuropathic pain. Here, we review an emerging number of investigations that suggest a pivotal role of impaired autophagy of GABAergic interneurons in NP. We discuss relevant research spurring the development of new targets and therapeutic agents of NP and emphasize the need for a multidisciplinary approach to manage NP in the future.

Reactive oxygen species affect spinal cell type-specific synaptic plasticity in a model of neuropathic pain.

Spinal synaptic plasticity is believed to drive central sensitization that underlies the persistent nature of neuropathic pain. Our recent data showed that synaptic plasticity in the dorsal horn is cell type specific: intense afferent stimulation produced long-term potentiation (LTP) in excitatory spinothalamic tract neurons (STTn), whereas it produced long-term depression (LTD) in inhibitory GABAergic interneurons (GABAn). In addition, reactive oxygen species (ROS) were shown to be involved in LTP in STTn (STTn-LTP) and in LTD in GABAn (GABAn-LTD). This study examined the roles of 2 biologically important ROS--superoxide [·O2] and hydroxyl radicals [·OH]--in neuropathic mechanical hyperalgesia and cell type-specific spinal synaptic plasticity. The [·O2] donor induced stronger mechanical hyperalgesia than the [·OH] donor in naive mice. The [·O2] scavenger showed greater antihyperalgesic effect than [·OH] scavengers in the spinal nerve ligation (SNL) mouse model of neuropathic pain. In addition, the [·O2] donor induced both STTn-LTP and GABAn-LTD, but the [·OH] donor induced only GABAn-LTD. On the other hand, the [·O2] scavenger inhibited STTn-LTP and GABAn-LTD induction in naive mice and alleviated SNL-induced potentiation in STTn and depression in GABAn. The [·OH] scavenger, however, inhibited depression in GABAn but did not interfere with potentiation in STTn. These results indicate that mechanical hyperalgesia in SNL mice is the result of the combination of STTn-LTP and GABAn-LTD. Behavioral outcomes compliment electrophysiological results which suggest that [·O2] mediates both STTn-LTP and GABAn-LTD, whereas [·OH] is involved primarily in GABAn-LTD.

Single high‐concentration capsaicin application prevents c‐Fos expression in spinothalamic and postsynaptic dorsal column neurons after surgical incision

Allodynia and hyperalgesia present after surgical interventions are often a major complain of surgical patients. It is thought that both peripheral and central mechanisms contribute to these symptoms. In this study, the role of peripheral nerve fibres that express transient receptor potential vanilloid 1 (TRPV1) receptors in the activation of spinothalamic tract (STT) and postsynaptic dorsal column (PSDC) neurons was assessed in a model of surgical pain. Spinothalamic tract and PSDC neurons retrogradely labelled from the thalamus and nucleus gracilis were used. Activation of these projection neurons was evaluated after plantar incision as expression of the early gene product, c-Fos protein, in the nuclei of these neurons. There was a robust increase in c-Fos immunopositivity in the STT and PSDC neurons, in the control animals after a plantar incision. This increase in c-Fos expression was significantly attenuated in animals in which a single high-concentration capsaicin injection was made intradermally at the incision site 24h before the surgery. Our results suggest that activation of both STT and PSDC neurons is involved in development of pain states present after surgical incision and that TRPV1-containing peripheral nerve fibres are needed for c-Fos expression in these dorsal horn neurons after plantar incision.

Induction of long-term potentiation and long-term depression is cell-type specific in the spinal cord.

The underlying mechanism of chronic pain is believed to be changes in excitability in spinal dorsal horn (DH) neurons that respond abnormally to peripheral input. Increased excitability in pain transmission neurons, and depression of inhibitory neurons, are widely recognized in the spinal cord of animal models of chronic pain. The possible occurrence of 2 parallel but opposing forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD) was tested in 2 types of identified DH neurons using whole-cell patch-clamp recordings in mouse spinal cord slices. The test stimulus was applied to the sensory fibers to evoke excitatory postsynaptic currents in identified spinothalamic tract neurons (STTn) and GABAergic neurons (GABAn). Afferent conditioning stimulation (ACS) applied to primary afferent fibers with various stimulation parameters induced LTP in STTn but LTD in GABAn, regardless of stimulation parameters. These opposite responses were further confirmed by simultaneous dual patch-clamp recordings of STTn and GABAn from a single spinal cord slice. Both the LTP in STTn and the LTD in GABAn were blocked by an NMDA receptor antagonist, AP5, or an intracellular Ca chelator, BAPTA. Both the pattern and magnitude of intracellular Ca after ACS were almost identical between STTn and GABAn based on live-cell calcium imaging. The results suggest that the intense sensory input induces an NMDA receptor-dependent intracellular Ca increase in both STTn and GABAn, but produces opposing synaptic plasticity. This study shows that there is cell type-specific synaptic plasticity in the spinal DH.

Chronic at-level thermal hyperalgesia following rat cervical contusion spinal cord injury is accompanied by neuronal and astrocyte activation and loss of the astrocyte glutamate transporter, GLT1, in superficial dorsal horn

Neuropathic pain is a form of pathological nociception that occurs in a significant portion of traumatic spinal cord injury (SCI) patients, resulting in debilitating and often long-term physical and psychological burdens. While many peripheral and central mechanisms have been implicated in neuropathic pain, central sensitization of dorsal horn spinothalamic tract (STT) neurons is a major underlying substrate. Furthermore, dysregulation of extracellular glutamate homeostasis and chronic astrocyte activation play important underlying roles in persistent hyperexcitability of these superficial dorsal horn neurons. To date, central sensitization and astrocyte changes have not been characterized in cervical SCI-induced neuropathic pain models, despite the fact that a major portion of SCI patients suffer contusion trauma to cervical spinal cord. In this study, we have characterized 2 rat models of unilateral cervical contusion SCI that behaviorally result in chronic persistence of thermal hyperalgesia in the ipsilateral forepaw. In addition, we find that STT neurons are chronically activated in both models when compared to laminectomy-only uninjured rats. Finally, persistent astrocyte activation and significantly reduced expression of the major CNS glutamate transporter, GLT1, in superficial dorsal horn astrocytes are associated with both excitability changes in STT neurons and the neuropathic pain behavioral phenotype. In conclusion, we have characterized clinically-relevant rodent models of cervical contusion-induced neuropathic pain that result in chronic activation of both STT neurons and astrocytes, as well as compromise in astrocyte glutamate transporter expression. These models can be used as important tools to further study mechanisms underlying neuropathic pain post-SCI and to test potential therapeutic interventions.

Enhancing K–Cl co-transport restores normal spinothalamic sensory coding in a neuropathic pain model

Neuropathic pain is a widespread and highly debilitating condition commonly resulting from injury to the nervous system, one main sequela of which is tactile allodynia, a pain induced by innocuous mechanical stimulation of the skin. Yet, the cellular mechanisms and neuronal substrates underlying this pathology have remained elusive. We studied this by quantifying and manipulating behavioural and neuronal nociceptive thresholds in normal and pathological pain conditions. We found that, in both control rats and those with pain hypersensitivity induced by nerve injury, the nociceptive paw withdrawal threshold matches the response threshold of nociceptive-specific deep spinothalamic tract neurons. In contrast, wide dynamic range or multimodal spinothalamic tract neurons showed no such correlation nor any change in properties after nerve injury. Disrupting Cl(-) homeostasis by blocking K(+)-Cl(-) co-transporter 2 replicated the decrease in threshold of nociceptive-specific spinothalamic tract neurons without affecting wide dynamic range spinothalamic tract cells. Accordingly, only combined blockade of both GABAA- and glycine-gated Cl(-) channels replicated the effects of nerve injury or K(+)-Cl(-) co-transporter 2 blockade to their full extent. Conversely, rescuing K(+)-Cl(-) co-transporter 2 function restored the threshold of nociceptive-specific spinothalamic tract neurons to normal values in animals with nerve injury. Thus, we unveil a tight association between tactile allodynia and abnormal sensory coding within the normally nociceptive-specific spinothalamic tract. Thus allodynia appears to result from a switch in modality specificity within normally nociceptive-specific spinal relay neurons rather than a change in gain within a multimodal ascending tract. Our findings identify a neuronal substrate and a novel cellular mechanism as targets for the treatment of pathological pain.

Long-Term Potentiation of Excitatory Synaptic Strength in Spinothalamic Tract Neurons of the Rat Spinal Cord

Spinal dorsal horn nociceptive neurons have been shown to undergo long-term synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). Here, we focused on the spinothalamic tract (STT) neurons that are the main nociceptive neurons projecting from the spinal cord to the thalamus. Optical technique using fluorescent dye has made it possible to identify the STT neurons in the spinal cord. Evoked fast mono-synaptic, excitatory postsynaptic currents (eEPSCs) were measured in the STT neurons. Time-based tetanic stimulation (TBS) was employed to induce long-term potentiation (LTP) in the STT neurons. Coincident stimulation of both pre- and postsynaptic neurons using TBS showed immediate and persistent increase in AMPA receptor-mediated EPSCs. LTP can also be induced by postsynaptic spiking together with pharmacological stimulation using chemical NMDA. TBS-induced LTP observed in STT neurons was blocked by internal BAPTA, or Ni2+, a T-type VOCC blocker. However, LTP was intact in the presence of L-type VOCC blocker. These results suggest that long-term plastic change of STT neurons requires NMDA receptor activation and postsynaptic calcium but is differentially sensitive to T-type VOCCs.

Updated Neurophysiology of Itch

The unique physiological features of histamine-sensitive C-fibers and spinothalamic tract neurons support the hypothesis of itch specific pathway, whereas subsequent studies on cowhage-induced itch have provided evidence against it, suggesting the presence of multiple neural pathways for itch. Not only peripheral pruritogens but also spinal neural receptors are involved in the control of itch, and will be the target of treatment. Itch sensitization in chronic pruritus is another crucial factor that needs to be considered in the treatment. Neuropathic itch is the type of itch that occurs when nerve fibers are damaged or injured and spontaneous firing of nerves takes place, and plays a major role in itch accompanying some pathological conditions such as herpes zoster. The complexity of itch is due to the broad range of mediators involved and the large variety of neural mechanisms behind.

Pruriceptive spinothalamic tract neurons: physiological properties and projection targets in the primate

Itch of peripheral origin requires information transfer from the spinal cord to the brain for perception. Here, primate spinothalamic tract (STT) neurons from lumbar spinal cord were functionally characterized by in vivo electrophysiology to determine the role of these cells in the transmission of pruriceptive information. One hundred eleven STT neurons were identified by antidromic stimulation and then recorded while histamine and cowhage (a nonhistaminergic pruritogen) were sequentially applied to the cutaneous receptive field of each cell. Twenty percent of STT neurons responded to histamine, 13% responded to cowhage, and 2% responded to both. All pruriceptive STT neurons were mechanically sensitive and additionally responded to heat, intradermal capsaicin, or both. STT neurons located in the superficial dorsal horn responded with greater discharge and longer duration to pruritogens than STT neurons located in the deep dorsal horn. Pruriceptive STT neurons discharged in a bursting pattern in response to the activating pruritogen and to capsaicin. Microantidromic mapping was used to determine the zone of termination for pruriceptive STT axons within the thalamus. Axons from histamine-responsive and cowhage-responsive STT neurons terminated in several thalamic nuclei including the ventral posterior lateral, ventral posterior inferior, and posterior nuclei. Axons from cowhage-responsive neurons were additionally found to terminate in the suprageniculate and medial geniculate nuclei. Histamine-responsive STT neurons were sensitized to gentle stroking of the receptive field after the response to histamine, suggesting a spinal mechanism for alloknesis. The results show that pruriceptive information is encoded by polymodal STT neurons in histaminergic or nonhistaminergic pathways and transmitted to the ventrobasal complex and posterior thalamus in primates.

An Itch To Be Scratched

The description of itch (formally known as pruritus) as an "unpleasant sensation that elicits the desire or reflex to scratch" (Ikoma et al., 2006) is immediately familiar. Research in the field of pruritoception has added to our understanding of this area of sensory neurobiology as it pertains to both normal and pathological conditions. In particular, much progress has been made on the mechanisms and circuits of itch, which we review here.

Sensory Disturbances in Complex Regional Pain Syndrome: Clinical Observations, Autonomic Interactions, and Possible Mechanisms

To review mechanisms that might contribute to sensory disturbances and sympathetically-maintained pain in complex regional pain syndrome (CRPS). CRPS is associated with a range of sensory and autonomic abnormalities. In a subpopulation of patients, sympathetic nervous system arousal and intradermal injection of adrenergic agonists intensify pain. Mechanisms responsible for sensory abnormalities in CRPS include sensitization of primary afferent nociceptors and spinothalamic tract neurons, disinhibition of central nociceptive neurons, and reorganization of thalamo-cortical somatosensory maps. Proposed mechanisms of sympathetically-maintained pain include adrenergic excitation of sensitized nociceptors in the CRPS-affected limb, and interaction between processes within the central nervous system that modulate nociception and emotional responses. Central mechanisms could involve adrenergic facilitation of nociceptive transmission in the dorsal horn or thalamus, and/or depletion of bulbo-spinal opioids or tolerance to their effects. Sympathetic neural activity might contribute to pain and sensory disturbances in CRPS by feeding into nociceptive circuits at the site of injury or elsewhere in the CRPS-affected limb, within the dorsal horn, or via thalamo-cortical projections.

Quantitative analysis of spinothalamic tract neurons in adult and developing mouse

Understanding the development of nociceptive circuits is important for the proper treatment of pain and administration of anesthesia to prenatal, newborn, and infant organisms. The spinothalamic tract (STT) is an integral pathway in the transmission of nociceptive information to the brain, yet the stage of development when axons from cells in the spinal cord reach the thalamus is unknown. Therefore, the retrograde tracer Fluoro-Gold was used to characterize the STT at several stages of development in the mouse, a species in which the STT was previously unexamined. One-week-old, 2-day-old and embryonic-day-18 mice did not differ from adults in the number or distribution of retrogradely labeled STT neurons. Approximately 3,500 neurons were retrogradely labeled from one side of the thalamus in each age group. Eighty percent of the labeled cells were located on the side of the spinal cord contralateral to the injection site. Sixty-three percent of all labeled cells were located within the cervical cord, 18% in thoracic cord, and 19% in the lumbosacral spinal cord. Retrogradely labeled cells significantly increased in diameter over the first postnatal week. Arborizations and boutons within the ventrobasal complex of the thalamus were observed after the anterograde tracer biotinylated dextran amine was injected into the neonatal spinal cord. These data indicate that, whereas neurons of the STT continue to increase in size during the postnatal period, their axons reach the thalamus before birth and possess some of the morphological features required for functionality.

Bidirectional Neuron–Glia Interactions Triggered by Deficiency of Glutamate Uptake at Spinal Sensory Synapses

Bidirectional interactions between neurons and glial cells are crucial to the genesis of pathological pain. The mechanisms regulating these interactions and the role of this process in relaying synaptic input in the spinal dorsal horn remain to be established. We studied the role of glutamate transporters in the regulation of such interactions. On pharmacological blockade of glutamate transporters, slow inward currents (SICs) appeared spontaneously and/or were evoked by peripheral synaptic input in the spinal superficial dorsal horn neurons, including the spinothalamic tract neurons. We showed that the SICs were induced by the release of glutamate from glial cells. On inhibition of glutamate uptake, the stimulation-induced, synaptically released glutamate activated glial cells and caused glial cells to release glutamate. Glial-derived glutamate acted on extrasynaptic N-methyl-d-aspartate (NMDA) receptors mainly composed of NR2B receptors and generated SICs, which led to depolarization and action potential generation in superficial spinal dorsal horn neurons. Thus glutamate transporters regulate glutamatergic neuron-glia interactions at spinal sensory synapses. When glutamate uptake is impaired, glial cells function like excitatory interneurons-they are activated by peripheral synaptic input and release glutamate to activate postsynaptic neurons in spinal pain pathways.

Laminae-specific distribution of alpha-subunits of voltage-gated sodium channels in the adult rat spinal cord

While the voltage-gated sodium channels (VGSCs) are the key molecules for neuronal activities, the precise distribution of them in spinal cord is not clear in previous studies. We examined the expression of mRNAs for α-subunits of VGSC (Navs) in adult rat spinal cord before and 7 days after L5 spinal nerve ligation (SPNL) or complete Freund's adjuvant (CFA)-induced paw inflammation by in situ hybridization histochemistry, reverse transcription-polymerase chain reaction, and immunohistochemistry. Nav1.1 and Nav1.6 mRNAs were present in all laminae, except for lamina II, including the spinothalamic tract neurons in lamina I identified by retrograde tracing of Fluoro-gold. Nav1.2 mRNA was predominantly observed in the superficial layers (laminae I, II), and Nav1.3 mRNA was more restricted to these layers. All these transcripts were expressed by the neurons characterized by immunostaining for neuron-specific nuclear protein. Nav1.7 mRNA was selectively expressed by a half of motoneurons in lamina IX. No signals for Nav1.8 or Nav1.9 mRNAs were detected. Immunohistochemistry for Nav1.1, Nav1.2, Nav1.6, and Nav1.7 proteins verified some of these neuronal distributions. L5 SPNL decreased Nav1.1 and Nav1.6 mRNAs, and increased Nav1.3 and Nav1.7 mRNAs in the axotomized spinal motoneurons, without any changes in other laminae of L4–6 spinal segments. Intradermal injection of CFA did not cause any transcriptional change. Our findings demonstrate that spinal neurons have different compositions of VGSCs according to their location in laminae. Pathophysiological changes of spinal neuronal activity may due to post-transcriptional changes of VGSCs. Comparison with our previous data concerning the subpopulation-specific distribution of Nav transcripts in primary afferent neurons provides potentially specific targets for local analgesics at the peripheral nerve and spinal levels.

Changes of calcium binding protein expression in spinothalamic tract neurons after peripheral inflammation

Specific neuronal populations are known to express calcium binding proteins (CBP) such as calbindin (CB), parvalbumin (PV) and calretinin (CR). These CBP can act as calcium buffers that modify spatiotemporal characteristics of intracellular calcium transients and affect calcium homeostasis in neurons. It was recently shown that changes in neuronal CBP expression can have significant modulatory effect on synaptic transmission. Spinothalamic tract (STT) neurons form a major nociceptive pathway and they become sensitized after peripheral inflammation. In our experiments, expression of CBP in STT neurons was studied in a model of unilateral acute knee joint arthritis in rats. Altogether 377, 374 and 358 STT neurons in the segments L3-4 were evaluated for the presence of CB, PV and CR. On the contralateral (control) side 1%, 9% and 47% of the retrogradely labeled STT neurons expressed CB, PV and CR, respectively. On the ipsilateral (arthritic) side there was significantly more CB (23%) and PV (25%) expressing STT neurons, while the number of CR positive neurons (50%) did not differ. Our results show increased expression of fast (CB) and slow (PV) calcium binding proteins in STT neurons after induction of experimental arthritis. This suggests that change in CBP expression could have a significant effect on calcium homeostasis and possibly modulation of synaptic activity in STT neurons.

Network Actions of Pentobarbital in the Rat Mesopontine Tegmentum on Sensory Inflow Through the Spinothalamic Tract

The recent discovery of a barbiturate-sensitive "general anesthesia switch" mechanism localized in the rat brain stem mesopontine tegmental anesthesia area (MPTA) has challenged the current view of the nonspecific actions of general anesthetic agents in the CNS. In this study we provide electrophysiological evidence that the antinociception, which accompanies the behavioral state resembling general anesthesia following pentobarbital (PB) microinjections into the MPTA of awake rats, could be accompanied by the attenuation of sensory transmission through the spinothalamic tract (STT). Following bilateral microinjections of PB into the MPTA spontaneous firing rate (SFR), antidromic firing index (FI), and sciatic (Sc) as well as sural (Su) nerve-evoked responses (ER) of identified lumbar STT neurons in the isoflurane-anesthetized rat were quantified using extracellular recording techniques. Microinjections of PB into the MPTA significantly suppressed the SFR (47%), magnitudes of Sc- (26%) and Su-ER (36%), and FI (41%) of STT neurons. Microinjections of PB-free vehicle control did not alter any of the above-cited electrophysiological parameters. The results from this study suggest that antinociception, which occurs during the anesthesia-like state following PB microinjections into the MPTA, may be due, in part, to (in)direct inhibition of STT neurons via switching mechanism(s) located in the MPTA. This study provides a provenance for investigating electrophysiologically the actions on STT neurons of other current agents used clinically to maintain the state of general anesthesia.

Relief of itch by scratching: state-dependent inhibition of primate spinothalamic tract neurons

Itch is relieved by scratching, but the neural mechanisms that are responsible for this are unknown. Spinothalamic tract (STT) neurons respond to itch-producing agents and transmit pruritic information to the brain. We observed that scratching the cutaneous receptive field of primate STT neurons produced inhibition during histamine-evoked activity but not during spontaneous activity or activity evoked by a painful stimulus, suggesting that scratching inhibits the transmission of itch in the spinal cord in a state-dependent manner.

Transient receptor potential vanilloid type 1 receptor regulates glutamatergic synaptic inputs to the spinothalamic tract neurons of the spinal cord deep dorsal horn

The spinothalamic tract (STT) neurons in the spinal dorsal horn play an important role in transmission and processing of nociceptive sensory information. Although transient receptor potential vanilloid type 1 (TRPV1) receptors are present in the spinal cord dorsal horn, their physiological function is not fully elucidated. In this study, we examined the role of TRPV1 in modulating neuronal activity of the STT neurons through excitatory and inhibitory synaptic inputs. Whole-cell patch-clamp recordings were performed on STT neurons labeled by a retrograde fluorescent tracer injected into the ventral posterior lateral (VPL) nucleus of the thalamus. Capsaicin (1 μM) increased the frequency of miniature excitatory postsynaptic currents (mEPSC) without changing the amplitude or decay time constant of mEPSC. In contrast, capsaicin had no distinct effect on GABAergic miniature inhibitory postsynaptic currents (mIPSC). Capsazepine (10 μM), a TRPV1 receptor antagonist, abolished the effect of capsaicin on mEPSCs. Capsazepine itself did not affect the baseline amplitude and frequency of mEPSC. The effect of capsaicin on mEPSC was also abolished by removal of external Ca 2+, but not by treatment with Cd 2+. Furthermore, capsaicin increased the firing activity of the STT neurons and this increase in neuronal activity by capsaicin was abolished in the presence of non– N-methyl- d-aspartic acid (NMDA) and NMDA receptor antagonists, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) and (R)-amino-5-phosphonovaleric acid (APV). These data suggest that activation of TRPV1 potentiates the glutamate release from excitatory terminals of primary afferent fibers and subsequently increases the neural activity of STT neurons of the rat spinal cord deep dorsal horn.