Quantitative comparison of inhibition in spinal cord of nociceptive information by stimulation in periaqueductal gray or nucleus raphe magnus of the cat

The descending inhibition of spinal neuronal responses by focal electrical stimulation in the periaqueductal gray (PAG) or nucleus raphe magnus (NRM) was quantitatively studied and compared in the anesthetized, paralyzed cat. All 60 dorsal horn neurons studied were driven by electrical stimulation of hindlimb cutaneous nerves at strengths supramaximal for activation of A-alpha,delta- and C-fibers, and 52 also responded to noxious radiant heating (50 degrees C, 10 s) of the skin of the foot- or toepads; 8 units had receptive fields in the hairy skin of the hindlimb. All neurons studied also responded to mechanical stimuli; recording sites were located in laminae I-VI of the dorsal horn. The inhibition of spinal neuronal heat-evoked responses by stimulation in the PAG or NRM differed quantitatively when examined on the same spinal neurons. Inhibition of heat-evoked spinal neuronal responses occurred at a lower threshold of stimulation in the NRM than in the PAG. The mean intensity of stimulation in the NRM producing an attenuation to 50% of the control 50 degrees C heat-evoked response was significantly lower than the mean intensity of stimulation in the PAG producing a 50% attenuation of the same spinal units. The mean magnitude of inhibition produced by stimulation in the NRM was significantly greater than that produced on the same spinal units by the same intensity of stimulation in the PAG. However, stimulation in the NRM and PAG produced the same mean percent change in inhibition per 100-microA increase in the intensity of stimulation. Thus, the slopes of the recruitment of descending inhibition from the PAG and the NRM as a function of increasing intensities of stimulation are the same; the lines of recruitment of inhibition are parallel. When examined on the same dorsal horn units, stimulation in the PAG influenced their intensity coding to graded noxious heating of the skin differently than did stimulation in the NRM. The responses of the class 2 and class 3 spinal units examined to increasing temperatures of heat applied to the skin was a monotonic linear function throughout the temperature range studied (42-50 degrees C). Stimulation in the PAG decreased the slope of the stimulus-response function (SRF) without affecting unit thresholds of response, thus influencing the gain control of nociceptive transmission in the dorsal horn. Stimulation in the NRM produced a parallel shift to the right of the SRF, influencing the set point and threshold of response.(ABSTRACT TRUNCATED AT 400 WORDS)     

Spinal pathways mediating tonic, coeruleospinal, and raphe-spinal descending inhibition in the rat

1. The contribution of midline medullary bulbospinal neurons to descending inhibition from the locus coeruleus (LC) and the funicular trajectories of coeruleo- and raphe-spinal fibers mediating inhibition of spinal nociceptive transmission were examined in different experiments. Extracellular recordings of lumbar dorsal horn neurons were made in deeply pentobarbital-anesthetized, paralyzed rats. All units studied responded to electrical stimulation of the ipsilateral tibial nerve at intensities supramaximal to activate A-alpha-delta- and C-fibers and to mechanical and heat (50 degrees C) stimuli of the glabrous skin of the ipsilateral hind foot. Parallel studies were done in lightly pentobarbital-anesthetized rats utilizing the nociceptive tail-flick (TF) reflex. 2. To examine the contribution of bulbospinal neurons in the nucleus raphe magnus (NRM) to descending coeruleospinal inhibition, lidocaine microinjections were made into the NRM to produce a time-limited, reversible block. Lidocaine microinjections into the NRM effectively blocked NRM stimulation-produced inhibition of the TF reflex (prelidocaine stimulation thresholds were increased two to three times), but did not affect stimulation-produced inhibition from the LC. 3. In parallel electrophysiological studies, stimulation in the NRM inhibited heat-evoked dorsal horn unit activity to 31% of control, whereas stimulation in the LC/SC inhibited heat-evoked activity of the same units to 30% of control. Following NRM lidocaine microinjections, stimulation at the same intensity in the NRM no longer inhibited heat-evoked activity (93% of control), confirming the efficacy of the lidocaine block. LC stimulation-produced inhibition, however, was not affected by blockage of the NRM; heat-evoked unit activity was inhibited by LC stimulation to 39% of control. 4. The effects of ipsilateral and bilateral ventrolateral funiculus (VLF) lidocaine microinjections on spontaneous and heat-evoked unit activity were examined in other experiments. Spontaneous activity increased following ipsilateral VLF lidocaine microinjections for 13/18 units; decreases and no change in spontaneous activity were observed for three and two units, respectively. Heat-evoked unit activity was increased significantly following ipsilateral VLF lidocaine microinjections.(ABSTRACT TRUNCATED AT 400 WORDS)     

Inhibition of the responses of cat dorsal horn neurons to noxious skin heating by stimulation in medial or lateral medullary reticular formation

Summary Responses of single lumbar dorsal horn units to noxious radiant heating (50° C, 10 s) of glabrous footpad skin were recorded in cats anesthetized with sodium pentobarbital and 70% nitrous oxide. The heat-evoked responses of 37/40 units were reduced during electrical stimulation (100 ms trains, 100 Hz, 3/s, 25–600 A) in the medullary nucleus raphe magnus (NRM) and/or in laterally adjacent regions of the medullary reticular formation (MRF). Inhibition was elicited by stimulation in widespread areas of the medulla, but with greatest efficacy at ventrolateral sites. The magnitude of inhibition increased with graded increases in medullary stimulation intensity. Mean current intensities at threshold for inhibition or to produce 50% inhibition were higher for NRM than for MRF sites. Units' responses to graded noxious heat stimuli increased linearly from threshold (42–43° C) to 52° C. During NRM (5 units) or ipsilateral MRF stimulation (7 units), responses were inhibited such that the mean temperature-response functions were shifted toward higher temperatures with increased thresholds (1.5° and 1° C, respectively) and reduced slopes (to 60% of control). Contralateral MRF stimulation had a similar effect in 4 units. Inhibitory effects of NRM and MRF stimulation were reduced (by >25%) or abolished in 4/6 and 5/12 units, respectively, following systemic administration of the serotonin antagonist methysergide. Inhibitory effects from NRM, ipsi- and contralateral MRF were reduced or abolished in 2/9, 4/8 and 6/9 cases, respectively, following systemic administration of the noradrenergic antagonist phentolamine. These results confirm and extend previous studies of medullospinal inhibition and the role of monoamines, and are discussed in terms of analgesic mechanisms.     

Spinal pathways mediating tonic or stimulation-produced descending inhibition from the periaqueductal gray or nucleus raphe magnus are separate in the cat

1. The spinal pathways for tonic and stimulation-produced descending inhibition of spinal nociceptive neurons were investigated in anesthetized paralyzed cats. Reversible circumscribed blocks were produced at various depths in the lateral funiculi (LF) at L1-L2 using the microinjection of the local anesthetic lidocaine. The total amount of tonic descending inhibition in the absence of LF blocks was evaluated by monitoring the spinal neuronal activity during reversible spinalization by cold block and compared with the activity of the same neuron during LF blocks. Stimulation-induced descending inhibition of neuronal responses to noxious skin heating was produced by bipolar focal electrical stimulation in the periaqueductal gray (PAG) or nucleus raphe magnus (NRM) and compared with the inhibition of the same neurons during LF blocks. The relative significance of ipsi- and contralateral pathways in the dorsal, medial, or ventral aspects of the lateral funiculi for these types of descending inhibition are quantitatively described. 2. All 35 lumbar spinal dorsal horn neurons studied responded to noxious and innocuous mechanical and noxious thermal stimuli applied within the receptive fields on the glabrous skin of the hindlimb. Responses to noxious skin stimuli (50 degrees C, 10 s at 3-min intervals) were constant over time and served as a parameter to evaluate tonic and stimulation-produced descending inhibition. All neurons also responded to electrical stimulation of hindlimb cutaneous nerves supramaximal for the activation of A-beta-, delta-, and C-fibers. Neurons were located in laminae I-VI of the dorsal horn at L5-L7 levels. LF blocks were produced by the microinjection of 1 microliter lidocaine at each of one to six sites in the ipsilateral and/or contralateral LF 500, 1,500, and/or 2,500 microns below cord surface. 3. LF blocks ipsilateral to the recording sites in the cord significantly reduced tonic inhibition, with blocks in the dorsal part of the LF [i.e., the dorsolateral funiculus (DLF)] being equally effective to complete LF blocks. Stimulation-produced inhibition from PAG or NRM was, however, not significantly affected by ipsilateral LF blocks. 4. Contralateral LF blocks significantly reduced stimulation-produced descending inhibition and failed to affect tonic descending inhibition. Ventral LF blocks attenuated inhibition from the PAG but not from NRM, whereas DLF blocks were more effective on inhibition from the NRM. 5. Bilateral LF blocks significantly reduced tonic as well as stimulation-produced descending inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)     

大鼠中缝大核向脊髓投射神经元与神经降压素能终末的突触联系

神经降压素(NT)是中枢下行抑制系统的重要神经活性物质。本研究运用免疫组织化学与逆行追踪法相结合的双标技术,在电镜下观察NT能终末与中缝大核(NRM)向脊髓投射神经元的突触联系。在光镜下可见NT阳性纤维和终末散在分布于NRM,但未见NT阳性神经元;将HRP注入腰髓背角后,在NRM内可见比较密集的HRP逆标神经元。在电镜下可见NT阳性终末与HRP逆标神经元的胞体和树突形成以非对称性为主的轴-体突触和轴-树突触。上述结果说明NT可能调控NRM向脊髓背角投射神经元的活动,借此对伤害性信息向中枢的传递发挥抑制效应。     

Inhibition of spinal nociceptive information by stimulation in midbrain of the cat is blocked by lidocaine microinjected in nucleus raphe magnus and medullary reticular formation

The organization in the brain stem of descending inhibitory control of spinal nociceptive information was studied in anesthetized, paralyzed cats by quantitatively evaluating the effects of reversible blocks produced by lidocaine microinjected in the medial and/or lateral medulla. Spinal neuronal inhibition produced by stimulation in the nucleus raphe magnus (NRMS) was compared to the inhibition of the same dorsal horn neurons produced by stimulation 2 mm lateral in the medullary reticular formation (MRFS). When the inhibition produced by NRMS and/or MRFS was blocked by lidocaine microinjected in those medullary sites, the efficacy of spinal neuronal inhibition produced by stimulation in the midbrain periaqueductal gray (PAGS) and 4 mm lateral in the reticular formation (LRFS) was evaluated and compared with the inhibition produced before the intramedullary microinjection of lidocaine. All 32 spinal dorsal horn neurons studied responded to hindlimb cutaneous nerve stimulation at strengths supramaximal for activation of A-alpha,delta- and C-fibers, to mechanical stimuli applied to the skin, and 27 also responded to noxious radiant heating (50 degrees C, 10 s) of the skin of the foot- or toepads (5 units had receptive fields in the hairy skin of the hindlimb). The noxious heat-evoked responses of all units studied were inhibited by NRMS or MRFS. The mean threshold currents for spinal inhibition, the mean maximal inhibition produced, and the mean stimulation currents producing an attenuation to 50% of the control response to 50 degrees C skin heating did not differ between NRMS and MRFS. When quantitatively compared on the same spinal units, NRMS produced the same mean magnitude of inhibition as the same intensities of MRFS, and both NRMS and MRFS produced the same mean percent increment in inhibition per 100-microA increase in the intensity of brain stimulation. The responses of the spinal units studied to graded noxious heating of the skin was a monotonic linear function throughout the temperature range employed (42-50 degrees C). MRFS shifted this stimulus response function (SRF) to the right, raising significantly the threshold of response a mean 2.2 degrees C to noxious heating of the skin without significantly affecting the slope of the SRF. MRFS reduced the number of discharges of spinal units evoked by electrical A-alpha,beta-fiber stimulation of hindlimb cutaneous nerves in 4 of 10 units studied. NRMS similarly inhibited the A-alpha,beta-fiber-evoked responses of two of the same four units affected by MRFS but also affected two of the remaining six units not affected by MRFS.(ABSTRACT TRUNCATED AT 400 WORDS)     

Raphe magnus-induced descending inhibition of spinal nociceptive neurons is mediated through contralateral spinal pathways in the cat

In anesthetized cats, extracellular recordings were made from lumbar spinal dorsal horn neurons, driven by noxious radiant skin heating. Heat-evoked responses were inhibited during electrical stimulation in the medullary nucleus raphe magnus (NRM). To identify the spinal pathways mediating this descending inhibition, reversible blocks in the spinal cord white matter were produced by microinjection of the local anesthetic lidocaine. Descending inhibition from the NRM was significantly reduced during blocks in the dorsal and medial, but not ventral parts of the contralateral lateral funiculus (LF). Blocks at any site in the ipsilateral LF failed to affect NRM-induced descending inhibition. These results indicate that NRM-induced inhibition of nociceptive dorsal horn neurons is conveyed primarily in fibers descending in the contralateral spinal white matter.     

Descending inhibitory influences from periaqueductal gray, nucleus raphe magnus, and adjacent reticular formation. I. Effects on lumbar spinal cord nociceptive and nonnociceptive neurons

1. This study examined the inhibitory effects of conditioning stimuli delivered to the periaqueductal gray (PAG), nucleus cuneiformis (CU), nucleus raphe magnus (NRM), nucleus reticularis gigantocellularis (NGC), and nucleus reticularis magnocellularis (NMC) on functionally identified neurons of the lumbar spinal cord dorsal horn in chloralose-anesthetized or decerebrate cats. 2. Neurons were classified according to their responses to a variety of cutaneous stimuli as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR), or nociceptive specific (NS). The major aim of this study was to determine whether there was a difference in the effectiveness of the brain stem stimulation-produced inhibition of nociceptive (noci) neurons (consisting of both WDR and NS neurons) and the LTM non-nociceptive (nonnoci) neurons. There were no statistical differences in the susceptibility of WDR and NS neurons to brain stem-induced inhibition. 3. Most neurons tested could be inhibited by stimulation of any of the brain stem regions tested. In all cases the percentage of noci neurons inhibited from a given region was higher than the percentage of nonnoci neurons; however, this difference was only statistically significant in the case of NMC stimulation. 4. Threshold current intensities necessary to produce inhibition were determined for each neuron from each stimulation site. Although there was a trend for noci neurons to require slightly lower current intensities, there was in fact no statistically significant difference in the inhibitory thresholds between noci and nonnoci neurons for any of the regions tested. 5. A comparison of the mean threshold currents for the five regions studied revealed that the lowest stimulation currents were obtained in NMC with NRM, CU, NGC, and PAG, each requiring progressively higher current intensities in order to produce inhibition. 6. These results indicate that stimulation in PAG and NRM not only inhibits the responses of noci neurons but also those of nonnoci neurons. Moreover, stimulation in reticular regions adjacent to these two regions is effective in inhibiting the responses of both noci and nonnoci neurons.     

Descending control of spinal nociceptive transmission. Actions produced on spinal multireceptive neurones from the nuclei locus coeruleus (LC) and raphe magnus (NRM)

Summary The effects of electrical stimulation in the nuclei locus coeruleus (LC) and raphe magnus (NRM) were examined on the background and/or evoked discharge of neurones in the spinal dorsal horn of anaesthetized cats. These were qualitatively, and in most cases quantitatively similar, in their action on multireceptive neurones. In these neurones an inhibitory action on the discharge evoked by noxious cutaneous stimuli or by activation of A and C fibres was most prominent although in some neurones (22%) an initial excitation lasting up to 100 ms preceded the inhibition which could last up to 1 s. Excitation alone was observed in only 3% of multireceptive neurones. Electrical stimulation also produced an inhibitory action on the discharge of low threshold mechanoreceptive neurones (80%). In four of ten multireceptive neurones examined in detail, LC stimulation produced a selective inhibitory action on the discharge evoked by noxious cutaneous stimuli. In the remaining six multireceptive neurones it was partially selective against noxious as compared with non-noxious inputs. The inhibitory action was also more pronounced on the discharge evoked by activity in A and C fibres than fast conducting afferents. The inhibitory action evoked by electrical stimulation in LC on nociceptive transmission in the spinal cord is suggested to play a part in mediating analgesia from LC.Abbreviation for Structures 6 Abducens nucleus - BC Brachium Conjunctivum - BP Brachium Pontis Dorsal Nucleus of Raphe - DRM Medial division - TD Dorsal Tegmental nucleus - 7L Facial Nucleus lateral division - 7M Facial Nucleus medial Division - V4 Fourth ventricle - 7G Genu of the Facial Nerve - IC Inferior Colliculus - SOL, SOM Lateral, Medial Nucleus of Superior Olive - BCM Marginal Nucleus of the Brachium conjunctivum - 5ME Mesencephalic trigeminal nucleus - 5M Motor Trigeminal Nucleus - LC Nucleus locus coeruleus - PH Nucleus praepositus hypoglossi - NRM Nucleus Raphe Magnus - P Pyramidal tract - PPR Postpyramidal Nucleus of the Raphe - SC Subcoeruleus - CS Superior Central Nucleus - TB trapezoid body     

Electrical stimulation of cervical vagal afferents. I. Central relays for modulation of spinal nociceptive transmission

1. Supraspinal relays for vagal afferent modulation of responses of spinal dorsal horn neurons to 50 degrees C heating of the skin were examined by the use of nonselective, reversible local anesthesia or soma-selective, irreversible neurotoxic damage of neural tissue. Eighty-five neurons were isolated in the lumbar spinal dorsal horn of 80 pentobarbital-anesthetized, paralyzed rats. All neurons studied had receptive fields on the glabrous skin of the plantar surface of the ipsilateral hind paw and responded to mechanical stimuli of both low and high intensity as well as noxious thermal stimulation. 2. Intensity-dependent modulation by vagal afferent stimulation (VAS) of neuronal responses to heating of the skin was established. Responses of 40 units were facilitated by low and inhibited by greater intensities of VAS. Another 36 units were only inhibited by VAS, and four were only facilitated. 3. Local anesthesia of the dorsolateral pons by bilateral microinjections of lidocaine (4%, 0.5 microliter) were made to examine the contribution of this area to VAS-produced spinal modulation. The microinjection of lidocaine bilaterally into the ventral locus coeruleus/subcoeruleus (LC/SC) reversibly and significantly attenuated VAS-produced inhibition of unit responses to heat from 63 to 89% of control and abolished VAS-produced facilitation. The microinjection of lidocaine bilaterally into the dorsal LC had no significant effect on VAS-produced modulation of spinal dorsal horn neurons. 4. Ibotenic acid (10 micrograms, 0.5 microliter) was microinjected into the dorsolateral pons to determine the relative contributions of cell bodies in this area to VAS-produced spinal modulation. Unilateral microinjection of ibotenic acid into the LC/SC ipsilateral to the vagus nerve stimulated had no significant effect on VAS-produced inhibition but significantly attenuated VAS-produced facilitation of unit responses to heat. Bilateral microinjections of ibotenic acid significantly attenuated VAS-produced inhibition of unit responses to heat from 48 to 94% of control. 5. Local anesthesia of the medial rostroventral medulla (RVM), primarily the nucleus raphe magnus (NRM), significantly attenuated VAS-produced inhibition of unit responses to heat from 55 to 87% of control but had no significant effect on VAS-produced facilitation. Microinjection of ibotenic acid into the RVM also significantly reduced VAS-produced inhibition of unit responses to heat. No significant change in VAS-produced spinal modulation was found after lidocaine microinjection into areas dorsal to the NRM, the nucleus raphe pallidus, or the olivary nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)     

延髓缝核SP神经元至脊髓背角的下行投射—HRP逆行追踪与免疫细胞化学结合法研究

将HRP分别注入18只大鼠的颈、胸、腰段脊髓背角内,应用HRP逆行追踪与免疫细胞化学结合法,对大鼠延髓缝核至脊髓背角的SP能下行投射进行了观察。至脊髓背角的SP能下行纤维主要来自大缝核(无明显定位关系),其次是隐缝核及苍白缝核。各缝核双标细胞占整个延髓缝核HRP标记细胞总数的百分比分别为:大缝核7.5％,隐缝核2.9％,苍白缝核1.4％。本文还讨论了延髓缝核SP能神经元至脊髓背角下行投射的机能意义。     

Projection of a cutaneous nerve to the spinal cord of the pigeon II. Responses of dorsal horn neurons

Summary The responses of dorsal horn neurons to both electrical stimulation of a cutaneous nerve and natural stimulation of skin receptors have been studied in an avian species, the pigeon. Neurons located in either lamina I or lamina IV were recorded. Most lamina IV neurons had short-latency responses to electrical stimulation of a cutaneous nerve and were activated by stimulation of sensitive mechanoreceptors. This points to an input from mechanoreceptors innervated by large afferent fibers. Lamina I neurons which were usually located near the entrance zone of small fibers had longer latency responses and had often an input from several groups of afferent fibers including C-fibers. Many lamina I neurons were activated specifically by noxious stimulation. Some had an input from sensitive mechanoreceptors but possibly through an additional synapse. A few lamina I neurons responded specifically to activation of cold receptors. Some dorsal horn neurons showed segmental inhibition. Altogether, the characteristics of dorsal horn neurons in the pigeon studied so far were similar to those in mammalian species.     

Dorsolateral pontine inhibition of dorsal horn cell responses to cutaneous stimulation: lack of dependence on catecholaminergic systems in cat

The effect of stimulating the dorsolateral pons (DLP) in the region of locus ceruleus (LC) on lumbar dorsal horn cell responses to innocuous and noxious cutaneous stimuli was assessed and the dependence of these effects on intact pontospinal catecholaminergic systems was tested in chloralose-anesthetized cats. DLP stimulation inhibited the responses of dorsal horn cells to both noxious and innocuous skin stimuli. The inhibitory effect was most prominent when the responses to noxious stimuli were tested. The thresholds for eliciting DLP-spinal inhibition were lowest (less than 30 microA) in the region of LC. The inhibitory effect was found in both ipsilateral and contralateral dorsal horns. The DLP-spinal inhibition was unaltered by depletion of spinal catecholamines brought about by repeated lumbar intrathecal administration of 6-hydroxydopamine or systemic administration of reserpine. We conclude that the DLP-dorsal horn inhibition is not related to a catecholaminergic ceruleospinal system in the cat and that the dependence of pain modulation by catecholamine systems is a reflection of other descending pathways.     

Quantitative characterization of ceruleospinal inhibition of nociceptive transmission in the rat

A total of 51 dorsal horn units responsive to heat were isolated and their receptive fields characterized (i.e., response properties and adequate stimuli determined) in pentobarbital-anesthetized, paralyzed rats. In 39 of the 51 units, the descending inhibition of heat-evoked activity produced by focal electrical stimulation in the locus ceruleus/subceruleus (LC/SC) was examined. All units studied responded to mechanical stimulation, to electrical stimulation of the ipsilateral tibial nerve at intensities supramaximal to activate A-alpha, delta- and C-fibers, and to noxious heating (50 degrees C) of the footpad. The cutaneous receptive fields of all units were confined to the glabrous skin of the toes and footpad. All neurons examined were located in the dorsal horn of the spinal cord in laminae I-VI. Tracking experiments established that inhibition of heat-evoked dorsal horn unit activity could be reliably produced by focal electrical stimulation in both the contralateral and ipsilateral LC/SC. The inhibition produced by electrical stimulation in the LC/SC was intensity-, pulse duration-, and frequency-dependent. In six experiments, the efficacy of LC/SC stimulation-produced inhibition of heat-evoked activity was compared using two pulse durations (100 and 400 microseconds); greater inhibition of heat-evoked activity was produced at lower intensities of stimulation at the 400-microseconds pulse duration. In 10 experiments, the frequency of stimulation was varied (25-200 Hz); stimulation at a frequency of 100 Hz resulted in maximal inhibition of heat-evoked activity for stimulation sites both inside (n = 7) and outside (n = 3) the LC/SC. Inhibition of heat-evoked dorsal horn unit activity could be reliably produced by focal electrical stimulation in sites inside the LC/SC (n = 18). Significant descending inhibition of noxious heat-evoked spinal neuronal activity could also be produced by stimulation in pontine sites located outside the LC/SC, however, not as reliably. Systematic electrode tracks were made through the pons, using a searching stimulus of 100 microA, to locate sites medial, lateral, and ventral to the LC/SC from which significant descending inhibition could be produced. Stimulation in 156 sites outside the LC/SC at 100 microA produced inhibition of heat-evoked spinal unit activity to 50% of control or less in only 37 sites. Descending inhibition was characterized quantitatively from 14 of these 37 sites; the mean intensities of stimulation to inhibit heat-evoked activity to 50% of control were experimentally determined, and the mean thresholds of stimulation for inhibition and the mean recruitment indices were calculated.(ABSTRACT TRUNCATED AT 400 WORDS)     

Functional properties of dorsal horn neurons that project to the dorsal accessory olive

1. This study examined the responses to natural cutaneous stimuli of neurons in the dorsal horn of the lumbosacral spinal cord that project to the dorsal accessory portion of the inferior olive (DAO) in cats anesthetized with pentobarbital sodium. Extracellular activity was recorded from single units antidromically activated by currents of less than or equal to 70 muA applied to DAO. 2. A total of 119 antidromically activated neurons was examined. Their antidromic activation latencies displayed a wide range (2.5-24.6 ms). The average latency corresponds to a conduction velocity of 24 m/s. 3. Collision was demonstrated for 24 neurons. All responded to some form of natural cutaneous stimulation. Their receptive fields encompassed some portion of the hind limb, particularly the toes; one-third displayed gradients of sensitivity. 4. Based on their thresholds to peripheral stimulation, the 24 neurons fell into five categories, those sensitive to light cutaneous stimuli (i.e., hair movement or light touch; 37.5%), rub (21%), tap (21%), pressure (12.5%), or noxious stimuli (8%). 5. Comparison of these results with data on the other major source of somatosensory information for DAO, the gracile nucleus (examined previously with the same methods), suggests that the sensitivity of neurons in DAO to light cutaneous stimuli is mediated primarily by neurons in the dorsal horn. The sensitivity of neurons in DAO to tap, rub, or pressure, on the other hand, might be mediated by neurons in either the dorsal horn, the gracile nucleus, or both.     

Inhibition of spinal nociceptive neurons by excitation of cell bodies or fibers of passage at various brainstem sites in the cat

The relative contribution of cells of origin and fibers of passage to the inhibition of spinal nociceptive neurons from various brainstem sites is not known. The present study therefore quantitatively compares the descending inhibition produced by focal electrical stimulation which indiscriminatively excites all neuronal elements with the inhibition evoked by glutamate microinjections which selectively excite cell bodies at the same sites within the midbrain periaqueductal gray (PAG) and neighboring lateral reticular formation (LRF) and within the medullary nucleus raphe magnus (NRM). In pentobarbital anesthetized cats extracellular recordings were made from 22 lumbar dorsal horn neurons responding to innocuous mechanical skin stimuli and to noxious radiant heating of the glabrous skin at the ipsilateral hindpaw. Glutamate microinjections (1 microliter, 0.5 M) into 6 of 10 sites within the NRM reduced heat-evoked responses in 6 different cats to 69.2 +/- 3.8% of control. Electrical stimulation (180-600 microA) at the same sites and two additional sites in the NRM reduced responses to 50.0 +/- 8.7% of control. At 4 of 10 sites within the PAG glutamate reduced spinal neuronal responses to heat in 4 different cats to 69.4 +/- 6.1% of control. Electrical stimulation at 3 of the same sites and 6 additional sites within the PAG reduced heat-evoked responses to 52.7 +/- 3.5% of control. Microinjections of glutamate into the LRF failed to affect heat-evoked responses in any of the 8 experiments tested, while electrical stimulation at 6 of the same sites in the LRF reduced neuronal responses to heat to 52.4 +/- 7.1% of control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bulbar raphe neurones with projections to the trigeminal nucleus caudalis and the lumbar cord in the rat: A fluorescence double-labelling study

Retrograde transport of the fluorescent dyes Evans blue and 4,6-diamidino-2-phenyl indole (DAPI) has been used to study projections from the medullary raphe nuclei to the trigeminal nucleus caudalis and to the dorsolateral quadrant of the thoracolumbar cord in the rat. The majority of projecting neurones were found in n. raphe magnus (NRM) and its ventrolateral extensions over the pyramids and inferior olive. Double labelling experiments showed that 94% of raphe-trigeminal neurones sent a collateral branch to the nucleus in the contralateral brainstem. Similarly, 92% of raphe-trigeminal neurones branched to supply the thoracolumbar cord. It is suggested that the widespread nature of the analgesia produced by electrical stimulation in NRM in conscious animals may be due to activation of a population of raphe neurones which inhibit the responses of neurones in the trigeminal nucleus and dorsal horn via an extensive system of collateral projections to these structures.     

Ventrolateral and dorsolateral ascending spinal cord pathway influence on thalamic nociception in cat

1. In cat there are two portions of the spinothalamic tract (STT)--a ventral component, the ventral spinothalamic tract (VSTT) made up of axons of cells of spinal cord laminae IV-X, and a dorsolateral component, the dorsolateral spinothalamic tract (DSTT) made up of axons of cells in lamina I of the spinal cord dorsal horn. This study was designed to evaluate thalamic neuronal responses to cutaneous noxious thermal stimuli and to determine the functional importance of pathways ascending in the ventral and dorsolateral portions of the spinal cord, ipsilateral to the thalamic recording site and contralateral to the hindlimb stimulation region, for transmission of nociceptive information to the thalamus. 2. Extracellular single-unit recordings were made from 45 neurons in the ventrobasal complex (VBX) of cat thalamus. Thirty-five of these units responded either exclusively or preferentially to noxious cutaneous stimuli. Responses to noxious thermal stimuli applied to the unit's receptive fields were obtained, and then the effects on these responses of blocking conduction through the dorsolateral funiculus (DLF) and the ventrolateral quadrant (VQ) of the thoracic spinal cord ipsilateral to the thalamic recording site were determined. DLF and VQ conduction blocks were accomplished with the use of a cold probe technique and, at times, surgical lesions of the appropriate portion of the spinal cord. 3. The nociceptive units were located in the periphery of the ventral posterior lateral nucleus (VPL) of the thalamus. Their locations corresponded to the somatotopic organization of VPL. Nociceptive thermal responses were found in both high-threshold (HT) (10 cells) and wide-dynamic-range (WDR) (22 cells) units. The receptive fields of these units were generally small and were located on the hindlimb contralateral to the recording site. The thermoreceptive units had thresholds between 44 and 48 degrees C and were able to code for stimulus intensity. 4. Nine of the 35 nociceptive units demonstrated a decrease in response and two units an increase in response to noxious cutaneous stimulation during DLF block ipsilateral to the recording site and contralateral to the cutaneous stimulation site, whereas four units demonstrated a decrease in response and one unit an increase in response to noxious thermal cutaneous stimulation during VQ block ipsilateral to the recording site and contralateral to the cutaneous stimulation site.(ABSTRACT TRUNCATED AT 400 WORDS)     

Modulation of cortical evoked potentials by stimulation of nucleus raphe magnus in rats.

1. In pentobarbital sodium-anesthetized rats, we evaluated changes in cortical evoked potentials (EPs) associated with electrical and chemical stimulation of nucleus raphe magnus (NRM). A condition-test (C-T) paradigm was used. Cortical EPs were produced by test stimuli delivered to a hindpaw or the thalamic ventral posterior lateral nucleus (VPL; electrical stimulation), or by photic stimulation of the eyes or electrical stimulation of contralateral homotopical cortex (transcallosal EPs). These test stimuli were then preceded by electrical or chemical conditioning stimulation (CS) delivered to NRM through a stereotaxically implanted electrode or injection cannula, respectively. Effects of CS on EPs produced by the test stimuli were characterized. 2. Electrical CS preceding a test stimulus delivered to the foot reduced the amplitude of EPs at thresholds as low as 10-25 microA. The magnitude of EP reduction was dependent on CS intensity, frequency, and the C-T interval. Optimal parameters were trains of 10 pulses (400 Hz) delivered at a C-T interval of 5-10 ms. Injection of glutamate and lidocaine into NRM demonstrated that these effects were due to activation of NRM neurons and not to current spread to medial lemniscus (ML). NRM CS also reduced cortical EPs produced by test stimulation in VPL but did not alter EPs from visual stimulation or from electrical stimulation of contralateral homotopical cortex. 3. These findings suggest that NRM CS attenuates EPs by inhibiting thalamic or thalamocortical afferent activity. Because NRM CS affected all components of the cortical EPs, the effect appears to involve alteration of general sensory activity and is not nociception specific.(ABSTRACT TRUNCATED AT 250 WORDS)     

Responses of spinocervical tract neurones to noxious stimulation of the skin.

1. Activity of single spinocervical tract neurones has been recorded in the lumbar spinal cord of chloralose anaesthetized or decerebrated cats. Reversible spinalization was produced by cold block at L3. Sensitivity of these neurones to noxious stimulation was studied by heating their cutaneous receptive fields above 40-45 degrees C. 2. Most of the units were located in lamina IV of the dorsal horn and had their receptive fields in the ipsilateral foot. All but one of the studied neurones were excited by moving hairs or by gentle mechanical stimulation of the skin. 3. Eighty-four % of the units were affected by noxious stimuli and three kinds of response were obtained: (i) 61% were excited (E-cells) by noxious heat; (ii) 19% were inhibited (I-cells); and (iii) 19% gave a mixed response reversing from excitatory to inhibitory (EI-cells). 4. E-cells had axons with a wider range of conduction velocities than the rest and also received the strongest descending inhibition from supraspinal structures. 5. The recording sites of EI-cells were located in the medial third of the dorsal horn whereas E- and I-cells were distributed over the full width of the dorsal horn. 6. The possible role of the spinocervical tract in nociception is discussed.