Changes in c-Fos expression induced by noxious stimulation in the trigeminal spinal nucleus caudalis and C1 spinal neurons of rats after hyperbaric exposure.
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The present study aims to test the hypothesis that hyperbaric exposure inhibits nociceptive processing in the trigeminal spinal nucleus caudalis and C1 spinal neurons. We investigated the c-Fos-like immunoreactivity of the brainstem and upper cervical spinal cord (C1 region) following an injection of mustard oil (15 microliters of 20%) into the nasal mucosa of pentobarbital anesthetized rats after exposure to hyperbaric (2-atmospheres, 1 h) and normobaric pressures. After the hyperbaric exposure, the mean number of Fos-immunoreactive neurons in the ipsilateral laminae I-II and III-IV of the trigeminal spinal nucleus caudalis were significantly lower than those in the normobaric condition. Similarly, the mean number of c-Fos positive neurons in the superficial layer (I-II) of the ipsilateral C1 segment were significantly reduced as compared with that in the normobaric condition. When treated with the vehicle alone, no significant difference was detected in the numbers of c-Fos positive neurons in the trigeminal spinal nucleus caudalis and C1 regions between hyperbaric and normobaric conditions. These results suggest that hyperbaric exposure may attenuate nociceptive signals from the area innervated by the trigeminal nerves at the level of both the trigeminal spinal nucleus caudalis and C1 dorsal horn. (+info)
Responses of medullary dorsal horn neurons to corneal stimulation by CO(2) pulses in the rat.
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Corneal-responsive neurons were recorded extracellularly in two regions of the spinal trigeminal nucleus, subnucleus interpolaris/caudalis (Vi/Vc) and subnucleus caudalis/upper cervical cord (Vc/C1) transition regions, from methohexital-anesthetized male rats. Thirty-nine Vi/Vc and 26 Vc/C1 neurons that responded to mechanical and electrical stimulation of the cornea were examined for convergent cutaneous receptive fields, responses to natural stimulation of the corneal surface by CO(2) pulses (0, 30, 60, 80, and 95%), effects of morphine, and projections to the contralateral thalamus. Forty-six percent of mechanically sensitive Vi/Vc neurons and 58% of Vc/C1 neurons were excited by CO(2) stimulation. The evoked activity of most cells occurred at 60% CO(2) after a delay of 7-22 s. At the Vi/Vc transition three response patterns were seen. Type I cells (n = 11) displayed an increase in activity with increasing CO(2) concentration. Type II cells (n = 7) displayed a biphasic response, an initial inhibition followed by excitation in which the magnitude of the excitatory phase was dependent on CO(2) concentration. A third category of Vi/Vc cells (type III, n = 3) responded to CO(2) pulses only after morphine administration (>1.0 mg/kg). At the Vc/C1 transition, all CO(2)-responsive cells (n = 15) displayed an increase in firing rates with greater CO(2) concentration, similar to the pattern of type I Vi/Vc cells. Comparisons of the effects of CO(2) pulses on Vi/Vc type I units, Vi/Vc type II units, and Vc/C1 corneal units revealed no significant differences in threshold intensity, stimulus encoding, or latency to sustained firing. Morphine (0.5-3.5 mg/kg iv) enhanced the CO(2)-evoked activity of 50% of Vi/Vc neurons tested, whereas all Vc/C1 cells were inhibited in a dose-dependent, naloxone-reversible manner. Stimulation of the contralateral posterior thalamic nucleus antidromically activated 37% of Vc/C1 corneal units; however, no effective sites were found within the ventral posteromedial thalamic nucleus or nucleus submedius. None of the Vi/Vc corneal units tested were antidromically activated from sites within these thalamic regions. Corneal-responsive neurons in the Vi/Vc and Vc/C1 regions likely serve different functions in ocular nociception, a conclusion reflected more by the difference in sensitivity to analgesic drugs and efferent projection targets than by the CO(2) stimulus intensity encoding functions. Collectively, the properties of Vc/C1 corneal neurons were consistent with a role in the sensory-discriminative aspects of ocular pain due to chemical irritation. The unique and heterogeneous properties of Vi/Vc corneal neurons suggested involvement in more specialized ocular functions such as reflex control of tear formation or eye blinks or recruitment of antinociceptive control pathways. (+info)
Parallel streams for the relay of vibrissal information through thalamic barreloids.
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This study investigated the organization of a vibrissal pathway that arises from the interpolar division of the spinal trigeminal complex (SP5i), transits through the ventral posterior medial nucleus (VPM), and innervates the somatosensory cortical areas in the rat. Using Fluoro-Gold and biotinylated dextran amine, respectively, as retrograde and anterograde tracers, the following organization plan was disclosed. The SP5i projection arises from a population of small-sized neurons that selectively innervate the ventral lateral part of VPM. In cytochrome oxidase-stained material, this region does not display any barreloid arrangement, but Fluoro-Gold injections in single barrel columns labeled rods of cells that extend caudally into the ventral lateral division of VPM. Thus, on the basis of retrograde labeling, barreloids were divided into core and tail compartments, which correspond to the rod segments running across the dorsal and ventral lateral parts of VPM, respectively. Double-labeling experiments revealed that SP5i afferents innervate the tail of barreloids. The anterograde labeling of thalamocortical axons show that most "core cells" project to a single barrel column, whereas some "tail cells" give rise to branching axons that innervate the second somatosensory area and the dysgranular zone of the barrel field. Injections that straddled the transition zone between the core and tail regions disclosed cells projecting to a single barrel column and to the surrounding dysgranular zone. These results suggest that the projection of "barreloids cells" to the granular and/or dysgranular zones relates to the class of prethalamic input(s) they receive. (+info)
Sensitization, desensitization and stimulus-induced recovery of trigeminal neuronal responses to oral capsaicin and nicotine.
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Repeated application of capsaicin at a 1-min interstimulus interval (ISI) to the tongue induces a progressively increasing irritant sensation (sensitization), followed after a rest period by reduced sensitivity to further capsaicin (desensitization). Sequential reapplication of capsaicin induces irritation that eventually increases to initial levels: stimulus-induced recovery (SIR). In contrast, repeated application of nicotine elicits a declining irritant sensation across trials. To investigate possible neural correlates of these phenomena, we recorded from single units in superficial laminae of the dorsomedial trigeminal subnucleus caudalis (Vc) that responded to noxious thermal (54 degrees C) and chemical (1 M pentanoic acid) stimulation of the tongue of anesthetized rats. We then recorded responses to either capsaicin (330 microM) or nicotine (0.6 M), delivered either once, repeatedly at 1-min ISI, or continually by constant flow. After the initial capsaicin application and a rest period, the capsaicin was reapplied in the identical manner to test for SIR. The mean response of 14 Vc units to sequential application of pentanoic acid did not vary significantly across trials, indicating lack of tachyphylaxis or sensitization. The averaged response of 11 Vc units to repeated capsaicin increased significantly across the first eight trials and then plateaued. Following the rest period, spontaneous firing had returned to the precapsaicin level. With capsaicin reapplication, the averaged response increased again after a significant delay (due to desensitization), but did not reattain the peak firing rate achieved in the initial series (partial SIR). Constant-flow application of capsaicin induced an identical sensitization followed by nearly complete SIR. A single application of capsaicin induced a significant rise in firing in eight other units, but the rate of rise and maximal firing rate were both much lower compared with repetitive or constant-flow capsaicin. When capsaicin was reapplied once after the rest period, there was no change in firing rate indicating absence of SIR. These results indicate that maintenance of the capsaicin concentration induces a progressive increase in neuronal response that parallels sensitization. With recurrent capsaicin application, desensitization can be overcome to result in a delayed recovery of Vc responses similar to SIR. In contrast, the averaged response of 17 Vc units to repeated or constant-flow application of nicotine increased only over the first 3 min, and then decreased to spontaneous levels even as nicotine was still being applied. These results are consistent with the decrease in the perceived irritation elicited by sequential application of nicotine in humans. (+info)
Differential projections of thermoreceptive and nociceptive lamina I trigeminothalamic and spinothalamic neurons in the cat.
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The projections of 40 trigeminothalamic or spinothalamic (TSTT) lamina I neurons were mapped using antidromic activation from a mobile electrode array in barbiturate anesthetized cats. Single units were identified as projection cells from the initial array position and characterized with natural cutaneous stimuli as nociceptive-specific (NS, n = 9), polymodal nociceptive (HPC, n = 8), or thermoreceptive-specific (COOL, n = 22; WARM, n = 1) cells. Thresholds for antidromic activation were measured from each electrode in the mediolateral array at vertical steps of 250 microm over a 7-mm dorsoventral extent in two to eight (median = 6.0) anteroposterior planes. Histological reconstructions showed that the maps encompassed all three of the main lamina I projection targets observed in prior anatomical work, i.e., the ventral aspect of the ventroposterior complex (vVP), the dorsomedial aspect of the ventroposterior medial nucleus (dmVPM), and the submedial nucleus (Sm). The antidromic activation foci were localized to these sites (and occasional projections to other sites were also observed, such as the parafascicular nucleus and zona incerta). The projections of thermoreceptive and nociceptive cells differed. The projections of the thermoreceptive-specific cells were 20/23 to dmVPM, 21/23 to vVP, and 17/23 to Sm, whereas the projections of the NS cells were 1/9 to dmVPM, 9/9 to vVP, and 9/9 to Sm and the projections of the HPC cells were 0/8 to dmVPM, 7/8 to vVP, and 6/8 to Sm. Thus nearly all thermoreceptive cells projected to dmVPM, but almost no nociceptive cells did. Further, thermoreceptive cells projected medially within vVP (including the basal ventral medial nucleus), while nociceptive cells projected both medially and more laterally, and the ascending axons of thermoreceptive cells were concentrated in the medial mesencephalon, while the axons of nociceptive cells ascended in the lateral mesencephalon. These findings provide evidence for anatomical differences between these physiological classes of lamina I cells, and they corroborate prior anatomical localization of the lamina I TSTT projection targets in the cat. These results support evidence indicating that the ventral aspect of the basal ventral medial nucleus is important for thermosensory behavior in cats, consistent with the view that this region is a primordial homologue of the posterior ventral medial nucleus in primates. (+info)
Potential role of medullary raphe-spinal neurons in cutaneous vasoconstriction: an in vivo electrophysiological study.
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In rabbits, raphe magnus/pallidus neurons form a link in the CNS pathway regulating changes in cutaneous blood flow elicited by nociceptive stimulation and activation of the central nucleus of the amygdala. To characterize relevant raphe-spinal neurons, we performed extracellular recordings from the rostral medullary raphe nuclei in anesthetized, paralyzed, mechanically ventilated rabbits. All studied neurons were antidromically activated from the dorsolateral funiculus of the spinal cord (C(8)-T(2)). Of 129 studied neurons, 40% were silent. The remaining neurons discharged spontaneously at 0.3-29 Hz. Nociceptive stimulation (lip squeeze with pliers) excited 63 (49%), inhibited 9 (7%), and did not affect 57 (44%) neurons. The same stimulation also elicited falls in ear pinna blood flow. In neurons activated by the stimulation, the increase in discharge preceded the fall in flow. Electrical stimulation of the spinal trigeminal tract excited 61/63 nociception-activated neurons [onset latencies range: 6-75 ms, mean: 28 +/- 3 (SE) ms], inhibited 9/9 nociception-inhibited neurons (onset latencies range: 9-85 ms, mean: 32 +/- 10 ms), and failed to affect 55/57 neurons insensitive to nociceptive stimulation. Neurons insensitive to nociceptive/trigeminal stimulation were also insensitive to nonnociceptive tactile stimulation and to electrical stimulation of the amygdala. They were either silent (32/45) or discharged regularly at low frequencies. They possessed long-duration action potentials (1.26 +/- 0.08 ms) and slow-conducting axons (6.0 +/- 0.5 m/s). These neurons may be serotonergic raphe-spinal cells. They do not appear to be involved in nociceptive-related cutaneous vascular control. Of the 63 neurons sensitive to nociceptive and trigeminal tract stimulation, 35 also responded to tactile stimulation (wide receptive field). These neurons possessed short action potentials (0.80 +/- 0.03 ms) and fast-conducting axons (30.3 +/- 3.1 m/s). In this subpopulation, electrical stimulation of the amygdala activated nearly all neurons tested (10/12), with a mean onset latency of 34 +/- 3 ms. The remaining 28 neurons sensitive to nociceptive and trigeminal stimulation did not respond to tactile stimuli and were mainly unaffected by amygdala stimulation. It may be that fast-conducting raphe-spinal neurons, with wide multimodal receptive fields and with input from the central nucleus of the amygdala, constitute the bulbo-spinal link in the CNS pathway regulating cutaneous blood flow in response to nociceptive and alerting stimuli. (+info)
Activation of spinobulbar lamina I neurons by static muscle contraction.
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Spinal lamina I neurons are selectively activated by small-diameter somatic afferents, and they project to brain stem sites that are critical for homeostatic control. Because small-diameter afferent activity evoked by contraction of skeletal muscle reflexly elicits exercise-related cardiorespiratory activation, we tested whether spinobulbar lamina I cells respond to muscle contraction. Spinobulbar lamina I neurons were identified in chloralose-anesthetized cats by antidromic activation from the ipsilateral caudal ventrolateral medulla. Static contractions of the ipsilateral triceps surae muscle were evoked by tibial nerve stimulation using parameters that avoid afferent activation, and arterial blood pressure responses were recorded. Recordings were maintained from 13 of 17 L(7) lamina I spinobulbar neurons during static muscle contraction, and 5 of these neurons were excited. Three were selectively activated only by muscle afferents and did not have a cutaneous receptive field. Spinobulbar lamina I neurons activated by muscle contraction provide an ascending link for the reflex cardiorespiratory adjustments that accompany muscular work. This study provides an important first step in elucidating an ascending afferent pathway for somato-autonomic reflexes. (+info)
Central sensitization of nociceptive neurons in trigeminal subnucleus oralis depends on integrity of subnucleus caudalis.
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Our recent studies have shown that application to the tooth pulp of the inflammatory irritant mustard oil (MO) produces a prolonged (>40 min) "central sensitization" reflected in neuroplastic changes in the mechanoreceptive field (RF) and response properties of nociceptive brain stem neurons in subnuclei oralis (Vo) and caudalis (Vc) of the trigeminal spinal tract nucleus. In view of the previously demonstrated ascending modulatory influence of Vc on Vo, our aim was to determine whether the Vo neuroplastic changes induced by MO application to the tooth pulp depend on an ascending influence from Vc. In chloralose/urethan-anesthetized rats, MO application to the pulp produced significant increases in Vo nociceptive neuronal orofacial RF size and responses to mechanical noxious stimuli that lasted as long as 40-60 min. These changes were not affected by vehicle (saline) microinjected into Vc at 20 min after MO application, but 0.3 microl of a 5 mM CoCl(2) solution microinjected into the ipsilateral Vc produced a reversible blockade of the MO-induced Vo neuroplastic changes. A similar volume and concentration of CoCl(2) solution injected into subnucleus interpolaris of the trigeminal spinal tract nucleus did not affect the MO-induced neuroplastic changes in Vo. These findings indicate that inflammatory pulp-induced central sensitization in Vo is dependent on the functional integrity of Vc. (+info)