15th Annual spring brain conference,march 10–13, 2004,summary report

The present study was designed (1) to characterize the subliminal responses of dorsal horn neurons to stimulation of the sural nerve, and (2) to correlate the type of response to this stimulus with the responses to natural mechanical stimulation of the skin. To accomplish this, intracellular and extracellular recordings were carried out in L⁶ and L⁷ dorsal horn neurons in the cat. The excitatory responses of each cell to electrical stimulation of the sural nerve and to mechanical stimulation of the skin were noted.

Of 35 dorsal horn cells recorded intracellularly, 11 responded with impulses to sural nerve stimulation, 9 responded with excitatory postsynaptic potentials (EPSPs) but not impulses, and 15 had no excitatory responses to this stimulus. The type of response to sural nerve stimulation was strongly correlated with receptive field modality. Most cells receiving an input from high-threshold cutaneous mechanoreceptors responded with impulses or gave no excitatory response to sural nerve stimulation, whereas most cells that had only low-threshold mechanoreceptor input responded with EPSPs only or gave no response. In cells with only low-threshold (LT) mechanoreceptive input, response to sural nerve stimulation was highly correlated with receptive field locus. Those LT cells with no excitatory responses to sural nerve stimulation had receptive fields confined to the foot and/or toes, whereas those that gave EPSPs had more proximal receptive fields. The possible significance of these data with reference to changes observed after lesions, such as increased response to sural nerve stimulation, increased receptive field size, and somatotopic reorganization, is discussed.     

Convergence of mechanosensory inputs onto neuromodulatory serotonergic neurons in the leech

By the frequency-dependent release of serotonin, Retzius neurons in the leech modulate diverse behavioral responses of the animal. However, little is known about how their firing pattern is produced. Here we have analyzed the effects of mechanical stimulation of the skin and intracellular stimulation of mechanosensory neurons on the electrical activity of Retzius neurons. We recorded the electrical activity of neurons in ganglia attached to their corresponding skin segment by segmental nerve roots, or in isolated ganglia. Mechanosensory stimulation of the skin induced excitatory synaptic potentials (EPSPs) and action potentials in both Retzius neurons in a ganglion. The frequency and duration of responses depended on the strength and duration of the skin stimulation. Retzius cells responded after T and P cells, but before N cells, and their sustained responses correlated with the activity of P cells. Trains of five impulses at 10 Hz in every individual T, P, or N cell in isolated ganglia produced EPSPs and action potentials in Retzius neurons. Responses to T cell stimulation appeared after the first impulse. In contrast, the responses to P or N cell stimulation appeared after two or more presynaptic impulses and facilitated afterward. The polysynaptic nature of all the synaptic inputs was shown by blocking them with a high calcium/magnesium external solution. The rise time distribution of EPSPs produced by the different mechanosensory neurons suggested that several interneurons participate in this pathway. Our results suggest that sensory stimulation provides a mechanism for regulating serotonin-mediated modulation in the leech.     

Role of different types of fibers of the infraorbital nerve in synaptic activation of masseter and digastric motoneurons

Postsynaptic potentials of motoneurons of the masseter and digastric muscles evoked by stimulation of the infraorbital nerve with a strength of between 1 and 10 thresholds were investigated in cats anesthetized with a mixture of chloralose and pentobarbital. Depending on their ability to be activated by low-threshold afferents of this nerve, motoneurons of the masseter were divided into two groups. Stimuli with a strength of 1.2–2.5 times above threshold for the most excitable fibers of the infraorbital nerve evoked short-latency EPSPs in the motoneurons of the first group; a further increase in stimulus strength (3–9 thresholds) led to the appearance of IPSPs with latent periods of 2.8–3.5 msec. Motoneurons of the second group responded to stimulation of the infraorbital nerve with a strength of 3–9 thresholds by IPSPs whose latent periods varied from 6 to 8 msec. Stimuli below 3 thresholds in strength evoked no responses in these motoneurons. Stimulation of the infraorbital nerve with pulses of between 1 and 2 thresholds in strength evoked EPSPs in digastric motoneurons, but an increase in the strength of stimulation led to action potential generation. The presence of many excitatory and inhibitory inputs formed by afferent fibers of different types evidently provides a basis for functional diversity of jaw-opening and jaw-closing reflexes.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 6, pp. 596–603, November–December, 1980.     

Millimeter wave effects on electrical responses of the sural nerve in vivo

Millimeter wave (MMW, 42.25 GHz)‐induced changes in electrical activity of the murine sural nerve were studied in vivo using external electrode recordings. MMW were applied to the receptive field of the sural nerve in the hind paw. We found two types of responses of the sural nerve to MMW exposure. First, MMW exposure at the incident power density ≥45 mW/cm² inhibited the spontaneous electrical activity. Exposure with lower intensities (10–30 mW/cm²) produced no detectable changes in the firing rate. Second, the nerve responded to the cessation of MMW exposure with a transient increase in the firing rate. The effect lasted 20–40 s. The threshold intensity for this effect was 160 mW/cm². Radiant heat exposure reproduced only the inhibitory effect of MMW but not the transient excitatory response. Depletion of mast cells by compound 48/80 eliminated the transient response of the nerve. It was suggested that the cold sensitive fibers were responsible for the inhibitory effect of MMW and radiant heat exposures. However, the receptors and mechanisms involved in inducing the transient response to MMW exposure are not clear. The hypothesis of mast cell involvement was discussed. Bioelectromagnetics 31:180–190, 2010. © 2009 Wiley‐Liss, Inc.     

Simultaneous Recording of Input and Output of Lateral Geniculate Neurones

TO understand the way in which the cat dorsal lateral geniculate nucleus (LGN) processes visual information it would be useful to know the number and type of retinal inputs to individual LGN neurones. Using electrical stimulation of the optic nerve Bishop et al.¹concluded that an impulse in a single optic nerve fibre is sufficient to excite a single LGN neurone. From the appearance of excitatory postsynaptic potentials (EPSPs) recorded essentially intracellularly, Creutzfeldt suggested that LGN neurones are driven by perhaps one² or a few³ retinal ganglion cells. Hubel and Wiesel⁴ proposed models of convergence of several retinal inputs on single LGN neurones based on analyses of receptive fields. Guillery⁵ produced anatomical evidence that some types of LGN neurones receive inputs from several different retinal fibres. Now we report direct observations which were made by recording simultaneously from single LGN neurones and from individual retinal ganglion cells which provided excitatory input to them. We shall not consider inhibitory influences, which are currently under study.     

Involvement of lysophosphatidic acid in bone cancer pain by potentiation of TRPV1 via PKCϵ pathway in dorsal root ganglion neurons

Background

Our previous study demonstrated that nitric oxide (NO) contributes to long-term potentiation (LTP) of C-fiber-evoked field potentials by tetanic stimulation of the sciatic nerve in the spinal cord in vivo. Ryanodine receptor (RyR) is a downstream target for NO. The present study further explored the role of RyR in synaptic plasticity of the spinal pain pathway.

Results

By means of field potential recordings in the adult male rat in vivo, we showed that RyR antagonist reduced LTP of C-fiber-evoked responses in the spinal dorsal horn by tetanic stimulation of the sciatic nerve. Using spinal cord slice preparations and field potential recordings from superficial dorsal horn, high frequency stimulation of Lissauer's tract (LT) stably induced LTP of field excitatory postsynaptic potentials (fEPSPs). Perfusion of RyR antagonists blocked the induction of LT stimulation-evoked spinal LTP, while Ins(1,4,5)P3 receptor (IP₃R) antagonist had no significant effect on LTP induction. Moreover, activation of RyRs by caffeine without high frequency stimulation induced a long-term potentiation in the presence of bicuculline methiodide and strychnine. Further, in patch-clamp recordings from superficial dorsal horn neurons, activation of RyRs resulted in a large increase in the frequency of miniature EPSCs (mEPSCs). Immunohistochemical study showed that RyRs were expressed in the dorsal root ganglion (DRG) neurons. Likewise, calcium imaging in small DRG neurons illustrated that activation of RyRs elevated [Ca²⁺]_i in small DRG neurons.

Conclusions

These data indicate that activation of presynaptic RyRs play a crucial role in the induction of LTP in the spinal pain pathway, probably through enhancement of transmitter release.     

High-frequency (300-800 Hz) components in cat geniculate (dLGN) early visual responses.

We analysed the early visual responses of relay cells of the dorsal part of cat lateral geniculate nucleus (dLGN) for the occurrence and characteristics of high-frequency (>300 Hz) spike patterns comparable to the high-frequency oscillations (HFO) found in the human somatosensory system. By using a special algorithm for correcting response latency, we can show that the vast majority of dLGN visual responses which were elicited by a sudden change in contrast show HFOs in the range of 300 to more than 800 Hz. After response time correction these HFOs are clearly visible in summed responses, indicating that these patterns are highly reproducible by identical stimuli. On this basis we analysed the HFOs in more detail. We found the oscillation frequency to increase with stimulus contrast and the area of the receptive field centre covered by an excitatory stimulus. Inhibition reduces the oscillation frequency as demonstrated with additional stimulation of the antagonistic surround of the receptive field and by blocking inhibition with micro-iontophoretical application of bicuculline methiodide. The HFO was almost independent of the state of the system as estimated from the EEG pattern. Based on these findings we discuss whether bursts of action potentials triggered by the low-threshold calcium spike (LTS) can contribute to this pattern of visual thalamic activity.     

Fictive locomotion and scratching inhibit dorsal horn neurons receiving thin fiber afferent input

In decerebrate paralyzed cats, we examined the effects of two central motor commands (fictive locomotion and scratching) on the discharge of dorsal horn neurons receiving input from group III and IV tibial nerve afferents. We recorded the impulse activity of 74 dorsal horn neurons, each of which received group III input from the tibial nerve. Electrical stimulation of the mesencephalic locomotor region (MLR), which evoked fictive static contraction or fictive locomotion, inhibited the discharge of 44 of the 64 dorsal horn neurons tested. The mean depth from the dorsal surface of the spinal cord of the 44 neurons whose discharge was inhibited by MLR stimulation was 1.77 +/- 0.04 mm. Fictive scratching, evoked by topical application of bicuculline to the cervical spinal cord and irritation of the ear, inhibited the discharge of 22 of the 29 dorsal horn neurons tested. Fourteen of the twenty-two neurons whose discharge was inhibited by fictive scratching were found to be inhibited by MLR stimulation as well. The mean depth from the dorsal surface of the cord of the 22 neurons whose discharge was inhibited by fictive scratching was 1.77 +/- 0.06 mm. Stimulation of the MLR or the elicitation of fictive scratching had no effect on the activity of 22 dorsal horn neurons receiving input from group III and IV tibial nerve afferents. The mean depth from the dorsal surface of the cord was 1.17 +/- 0.07 mm, a value that was significantly (P < 0.05) less than that for the neurons whose discharge was inhibited by either MLR stimulation or fictive scratching. We conclude that centrally evoked motor commands can inhibit the discharge of dorsal horn neurons receiving thin fiber input from the periphery.     

Postsynaptic potentials of motoneurons evoked by rubrofugal impulsation in the hypoglossal nucleus of the cat

The effect of stimulation of the ipsilateral and contralateral red nuclei on motoneurons of the hypoglossal nucleus was studied in cats anesthetized with chloralose and pentobarbital. In 35 (69%) of the 51 motoneurons tested, PSPs were generated in response to stimulation of the red nuclei by series of 3 to 5 stimuli of threshold strength and with a frequency of 500–600/sec. Of this number, 33 motoneurons responded to stimulation by EPSPs, whose latent periods varied from 3.5 to 14.0 msec (mean value for the ipsilateral red nucleus 5.7±0.75, for the contralateral nucleus 6.8±0.8 msec), whereas two motoneurons responded (after 6.2 msec) by IPSPs. Of the 35 motoneurons responding to stimulation of the red nuclei, stimulation of the lingual nerve evoked EPSPs in 31 and IPSPs in 4 (two of them were inhibited by rubrofugal impulses). IPSPs were generated as a result of stimulation of the lingual nerve in 16 motoneurons which did not respond to rubrofugal impulses.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 1, pp. 62–66, January–February, 1978.     

Evoked activity of spinal neurons in the early period after sciatic nerve division

The character of dorsal horn motoneurons and interneurons evoked by stimulation of the dorsal root, and activity of Renshaw cells in response to stimulation of the ventral root were studied in albino rats in the lower lumbar segments of the spinal cord 5 days after sciatic nerve division. A significant increase in the mean amplitude of excitatory postsynaptic potentials of motoneurons was observed on the side of division of the nerve. No significant change in membrane potential and in the threshold of appearance of the action potential of these motoneurons took place. The mean number of action potentials and the duration of discharge of the Renshaw cells and dorsal horn interneurons likewise were not significantly changed.Dnepropetrovsk Medical Institute, Ukrainian Ministry of Health. Translated from Neirofiziologiya, Vol. 24, No. 3, pp. 306–314, May–June, 1992.     

Changes in the activity of cells in the lateral geniculate nucleus by stimulation of the abducens nucleus area in rabbits

These investigations are aimed at studying the influence of the electrical stimulation of the VIth nucleus (abducens nucleus) on responses of lateral geniculate cells in rabbits. The animals were prepared in the usual fashion for single cell recordings at the lateral geniculate nucleus (LGN). Results show that: Electrical stimulation of the VIth nucleus always produced excitatory discharges whose latency varied from 30 to 400 ms. Interestingly, an electrical pulse applied to the abducens nucleus was capable of enhancing the light-evoked responses without altering the spontaneous rate of firing. It thus seems that the ascending influence of the VIth nucleus manifests itself when it coincides with light responses. Most cells which were sensitive to electrical activation of the abducens nucleus had their receptive field located peripherally (greater than 50 degrees). Histological reconstructions of recording electrode tracts suggest that cells which responded to electrical stimulation were located in a narrow band lying dorsally relative to the LGN. This area can be paralleled with the perigeniculate area observed in other mammals, although not identified in rabbits. It is suggested that these extraretinal impulses which reach the LGN and emerge from an area surrounding the VIth nucleus are associated with corollary discharges.     

Chronic effects of total or partial digit denervation on raccoon somatosensory cortex.

Electrophysiological recordings were made in the primary somatosensory cortex of anesthetized raccoons 14 to 169 days following digit amputation or 60 to 129 days after transection of the two nerves innervating the ventral surface of the fourth digit. The incidence of inhibitory responses decreased from 50% of the penetrations immediately after amputation to 35% over the first 3 weeks and to almost zero after 2 months. The number of sites with low-threshold excitatory responses increased from 4% to 14% to 50% during these same intervals. Initially, the excitatory fields were small and located over the nerve stumps, and were therefore probably due to direct stimulation of the damaged nerves. At 2 months after amputation, the excitatory receptive fields were large and diffuse. Although the size of receptive fields decreased during the later period (when the thresholds were also decreasing), there was no recovery of any precise somatotopic organization in the deafferented cortex. The reorganization process in the raccoon thus consists of at least two stages: The early stage is dominated by inhibitory connections, whereas the second involves a recovery and restructuring of excitatory inputs. From 2 to 4 months after partial digit denervation, there were only minor changes in response properties or somatotopic organization in the deafferented cortex as compared to immediately after nerve transection. Thus, few of the characteristics of reorganization induced by digit amputation were elicited by this treatment, which leaves some of the digit innervation intact. There was, however, an unexpected increase in the portion of the ventral digit that was able to activate the cortex, suggesting complexities in the peripheral innervation of the digit that need to be resolved.     

Synaptic activation of thoracic interneurons by reticulospinal fibers of the lateral funiculus

Synaptic responses of different functional groups of interneurons in segments T10 and T11 to stimulation of the ipsilateral and contralateral medullary reticular formation were investigated in anesthetized cats with only the ipsilateral lateral funiculus remaining intact. Activation of reticulospinal fibers of the lateral funiculus with conduction velocities of 30–100 m/sec was shown to induce short-latency and, in particular, monosynptic EPSPs in all types of cells tested: in interneurons excited by group Ia muscle afferents, in cells activated only by high-threshold cutaneous and muscle afferents (afferents of the flexor reflex), in cells activated mainly by descending systems, and, to a lesser degree, in neurons connected with low-threshold cutaneous afferents. These cell populations are located mainly in the central and lateral parts of Rexed's lamina VII. Most neurons in laminae I–V of the dorsal horn, except six cells located in the superficial layers of the dorsal horn, received no reticulofugal influences. The functional organization of connections of the lateral reticulospinal tract with spinal neurons is discussed and compared with the analogous organization of the medial reticulospinal tract, and also of the "lateral" (cortico- and rubrospinal) descending systems.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 2, pp. 150–161, March–April, 1978.     

电刺激猫中脑导水管周围灰质和中缝大核对脊髓背角神经元伤害性感受反应的抑制

1.在氯醛糖麻醉的猫上,观察了电刺激中脑导水管周围灰质(PAG)和中缝大核(NRM)对脊髓腰段背角神经元传入活动的影响。2.按照对刺激的反应型式,在背角记录到非伤害性低阈值传入、广动力范围、伤害性热敏以及高阈值传入诱发的自发放电抑制等四类神经元。3.刺激 PAG和 NRM对记录到的多数背角神经元皮肤传入反应有明显抑制效应,而对自发放电抑制性神经元产生去抑制。4.比较刺激两脑区的抑制效应:NRM 作用较PAG 强;PAG 活动对背角伤害性反应抑制的选择性较 NRM强;阿片肽拮抗剂-纳洛酮拮抗NRM刺激的抑制。5.这些结果提示PAG和NRM对脊髓的下行抑制,可能有一部分是通过不同神经机制实现的。     

Static and dynamic properties of synaptic transmission at the cyto- neural junction of frog labyrinth posterior canal

The properties of synaptic transmission have been studied at the cyto-neural junction of the frog labyrinth posterior canal by examining excitatory postsynaptic potential (EPSP) activity recorded intraaxonally from the afferent nerve after abolishing spike firing by tetrodotoxin. The waveform, amplitude, and rate of occurrence of the EPSPs have been evaluated by means of a procedure of fluctuation analysis devised to continuously monitor these parameters, at rest as well as during stimulation of the semicircular canal by sinusoidal rotation at 0.1 Hz, with peak accelerations ranging from 8 to 87 deg.s-2. Responses to excitatory and inhibitory accelerations were quantified in terms of maximum and minimum EPSP rates, respectively, as well as total numbers of EPSPs occurring during the excitatory and inhibitory half cycles. Excitatory responses were systematically larger than inhibitory ones (asymmetry). Excitatory responses were linearly related either to peak acceleration or to its logarithm, and the same occurred for inhibitory responses. In all units examined, the asymmetry of the response yielded nonlinear two-sided input-output intensity functions. Silencing of EPSPs during inhibition (rectification) was never observed. Comparison of activity during the first cycle of rotation with the average response over several cycles indicated that variable degrees of adaptation (up to 48%) characterize the excitatory response, whereas no consistent adaptation was observed in the inhibitory response. All fibers appeared to give responses nearly in phase with angular velocity, at 0.1 Hz, although the peak rates generally anticipated by a few degrees the peak angular velocity. From the data presented it appears that asymmetry, adaptation, and at least part of the phase lead in afferent nerve response are of presynaptic origin, whereas rectification and possible further phase lead arise at the encoder. To confirm these conclusions a simultaneous though limited study of spike firing and EPSP activity has been attempted in a few fibers.     

Functional organization of the electroreceptive midbrain in an elasmobranch (Platyrhinoidis triseriata)

The response properties of 322 single units in the electroreceptive midbrain (lateral mesencephalic nucleus, LMN) of the thornback ray, Platyrhinoidis triseriata, were studied using uniform and local electric fields. Tactile, visual, or auditory stimuli were also presented to test for multimodality. Most LMN electrosensory units (81%) are silent in the absence of stimulation. Those with spontaneous activity fired irregularly at 0.5 to 5 impulses/s, the lower values being more common. Two units had firing rates greater than 10/s. Midbrain electrosensory units are largely phasic, responding with one or a few spikes per stimulus onset or offset or both, but the adaptation characteristics of some neurons are complex. The same neuron can exhibit phasic or phasic-tonic responses, depending upon orientation of the electric field. Tonic units without any initial phasic over-shoot were not recorded. Even the phasic-tonic units adapt to a step stimulus within several seconds. Unit thresholds are generally lower than 0.3 microV/cm, the weakest stimulus delivered, although thresholds as high as 5 microV/cm were recorded, Neuronal responses reach a maximum, with few exceptions, at 100 microV/cm and decrease rapidly at higher intensities. LMN neurons are highly sensitive to stimulus repetition rates: most responded to frequencies of 5 pulses/s or less; none responded to rates greater than 10/s. Three distinct response patterns are recognized. Best frequencies in response to sinusoidal stimuli range from 0.2 Hz (the lowest frequency delivered) to 4 Hz. Responses decrease rapidly at 8 Hz or greater, and no units responded to frequencies greater than 32 Hz. Most LMN neurons have small, well defined excitatory electroreceptive fields (RFs) exhibiting no surround inhibition, at least as detectable by methods employed here. Seventy-eight percent of units recorded had RFs restricted to the ventral surface: of these, 98% were contralateral. The remaining 22% of units had disjunct dorsal and ventral receptive fields. Electrosensory RFs on the ventral surface are somatotopically organized. Anterior, middle, and posterior body surfaces are mapped at the rostral, middle, and caudal levels, respectively, of the contralateral LMN. The lateral, middle, and medial body are mapped at medial, middle, and lateral levels of the nucleus. Moreover, the RFs of all units isolated in a given dorsoventral electrode track are nearly superimposable. About 40% of LMN, measured from the dorsal surface, is devoted to input from ventral electroreceptors located in a small region rostral and lateral to the mouth.(ABSTRACT TRUNCATED AT 400 WORDS)     

Responses of neurons in cat primary somatosensory cortex to repetitive stimulation of vibrissae

Extra- and intracellular responses of neurons in the primary somatosensory cortex to repetitive mechanical stimulation of the vibrissae at different frequencies were studied in unanesthetized curarized adult cats. Unlike responses to electrical stimulation of the combined afferent input (the infraorbital nerve) spike discharges of neurons in response to vibrissal stimulation can reproduce rather higher frequencies of stimulation and their initial character changes more often in the course of the repetitive series. Most cortical neurons were characterized by limitation of the area of their peripheral receptive fields with an increase in the frequency of adequate repetitive stimulation. A group of cortical neurons was distinguished by its ability to respond to high-frequency stimulation and to generate burst discharges. Comparison of the frequency characteristics of spike responses of these cells and of inhibitory synaptic action in other cortical neurons led to the conclusion that this group of cells thus distinguished may be inhibitory cortical neurons. The role of interaction between excitatory and inhibitory processes arising in cortical neurons during repetitive stimulation of different areas of their receptive fields is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 14, No. 2, pp. 164–171, March–April, 1982.     

Prolonged primary afferent induced alterations in dorsal horn neurones, an intracellular analysis in vivo and in vitro

1.) Peripheral tissues injury produces long lasting sensory and motor disturbances in man that present as the post-injury hypersensitivity syndrome with a reduction in the threshold required to elicit either pain or the flexion withdrawal reflex and an exaggeration of the normal response to suprathreshold stimuli. 2.) Two mechanisms contribute to these changes; sensitization of the peripheral terminals of high threshold primary afferents and an increase in the excitability of the spinal cord; a phenomenon known as central sensitization. 3.) Central sensitization has previously been shown by our laboratory to be the consequence of activity in unmyelinated primary afferents. Brief (20 s) C-fibre strength conditioning stimuli have the capacity to produce both a prolonged heterosynaptic facilitation of the flexion reflex and an alteration in the response properties of dorsal horn neurones, that long outlast the conditioning stimulus. 4.) In the adult decerebrate-spinal rat preparation we have, using intracellular recordings of dorsal horn neurones, examined the time course of the central effects of different types of orthodromic inputs. The hemisected spinal cord preparation isolated from 12-14 day rat pups has been used to see whether prolonged alterations in dorsal horn properties induced by orthodromic inputs can be studied in vitro. 5.) Single stimuli applied to a cutaneous nerve at graded strengths to successively recruit A beta, A delta and C-afferents produce, in the majority of neurones recorded in the deep dorsal horn in vivo, a series of post synaptic potentials that last from between ten and several hundred milliseconds. 6.) Repeated low frequency stimulation of C but not A-afferent fibres results in a pattern of progressive response increment or windup in a proportion of dorsal horn neurones. In some of the neurones the windup is associated with a depolarization that outlasts the stimulus period for tens of seconds. 7.) Application of the chemical irritant mustard oil to the skin activates chemosensitive C-afferent fibres for 1-3 minutes. Such a conditioning stimulus results however in an expansion in the size and an alteration in the response properties of the receptive fields of dorsal horn neurones that lasts for tens of minutes. 8.) In dorsal horn neurones recorded intracellularly in the isolated hemisected spinal cord, both intrinsic membrane properties and the orthodromic responses to primary afferent input can be studied. Repeated stimulation of a dorsal root produces in some neurones a prolonged heterosynaptic facilitation with both an augmentation of the response to the conditioning root (homosynaptic potentiation) and to adjacent test roots (heterosynaptic potentiation).(ABSTRACT TRUNCATED AT 400 WORDS)     

Spinal cord sensory systems after neonatal capsaicin

Animals with a severe reduction in the number of afferent C-fibres as a consequence of neonatal administration of capsaicin, exhibit a number of neurological and behavioral deficits including increased nociceptive thresholds, altered somato-visceral and viscero-visceral reflexes, depressed cardiovascular and respiratory reflexes and changes in the organisation of spinal cord sensory systems. The reduction in the number of C-fibres produced by neonatal capsaicin does not cause a decrease of similar magnitude in the number of dorsal horn cells driven by the surviving C-fibres. Twenty-two per cent of dorsal horn neurones in capsaicin treated animals respond to electrical stimulation of the surviving afferent C-fibres: a reduction of only 50% from control values. Inhibitory controls on afferent C-fibre evoked responses of dorsal horn neurones are weaker in capsaicin treated rate than in control animals. The cutaneous receptive fields of some dorsal horn neurones can increase in size following stimulation of afferent C-fibres. Tonic descending inhibition on C-fibre evoked responses of dorsal horn neurones is reduced in capsaicin treated rats: fewer neurones show tonic descending inhibition in these animals and those that do are subjected to less powerful inhibitions than similar neurones from control animals. However, some central inhibitory mechanism are unchanged after neonatal capsaicin treatment, specially those that do not involve afferent C-fibres. We suggest that the nervous system develops central inhibition in response to and directed towards the excitations mediated by its afferent drives. Therefore reduced central inhibition in response to a decreased number of afferent C-fibres can compensate for the lost capacity in the signalling of peripheral noxious events.     

Dissociation of μ- and δ-opioid inhibition of glutamatergic synaptic transmission in superficial dorsal horn

Background

Although it has been widely accepted that the primary somatosensory (SI) cortex plays an important role in pain perception, it still remains unclear how the nociceptive mechanisms of synaptic transmission occur at the single neuron level. The aim of the present study was to examine whether noxious stimulation applied to the orofacial area evokes the synaptic response of SI neurons in urethane-anesthetized rats using an in vivo patch-clamp technique.

Results

In vivo whole-cell current-clamp recordings were performed in rat SI neurons (layers III-IV). Twenty-seven out of 63 neurons were identified in the mechanical receptive field of the orofacial area (36 neurons showed no receptive field) and they were classified as non-nociceptive (low-threshold mechanoreceptive; 6/27, 22%) and nociceptive neurons. Nociceptive neurons were further divided into wide-dynamic range neurons (3/27, 11%) and nociceptive-specific neurons (18/27, 67%). In the majority of these neurons, a proportion of the excitatory postsynaptic potentials (EPSPs) reached the threshold, and then generated random discharges of action potentials. Noxious mechanical stimuli applied to the receptive field elicited a discharge of action potentials on the barrage of EPSPs. In the case of noxious chemical stimulation applied as mustard oil to the orofacial area, the membrane potential shifted depolarization and the rate of spontaneous discharges gradually increased as did the noxious pinch-evoked discharge rates, which were usually associated with potentiated EPSP amplitudes.

Conclusions

The present study provides evidence that SI neurons in deep layers III-V respond to the temporal summation of EPSPs due to noxious mechanical and chemical stimulation applied to the orofacial area and that these neurons may contribute to the processing of nociceptive information, including hyperalgesia.