Subnucleus Reticularis Dorsalis Research Articles

Physiology of nociception

Nociception is related to the mechanisms elicited by stimuli threatening the integrity of the organism. At the peripheral level, unmyelinated C fibres (C polymodal nociceptores) or fine myelinated A delta fibres are excited by noxious stimulation, directly or indirectly by inflammatory processes. Nociceptive afferent fibres terminate in the superficial laminae of the dorsal horn of the spinal cord where informations are integrated and controlled. These first synapses are modulated by excitatory amino acids (glutamate and aspartate) and many peptides (substance P, CGRP, CCK, endogenous opiods). The majority of ascending pathways involved in nociception are located in the ventrolateral controlateral quadrant of the cord (spinorelicular and spinothalamic tracts). Many supraspinal sites are activated following nociceptive stimuli, with relays in the reticular formation of the brain stem (including the subnucleus reticularis dorsalis), the ponto-mesencephalic regions (periaqueducal gray matter and parabrachial area) and thalamic sites. Amygdala and hypothamic targets could be involved in motivational reactions and neuroendocrine adaptations to a noxious event. The cingular, insular and somatosensory cortices also receive nociceptive informations. Nociceptive signals are modulated at all levels of their transmission; the more extensively studied controls are located at the spinal level. Segmental controls are inhibitory effects produced by non-noxious mechanical stimuli. Spinal signals can also be inhibited following activation of bulbopinal descending inhibitor pathways and release of serotonin, norepinephrine and, indirectly, endogenous opiods. Inhibitory controls triggered by noxious stimuli could facilitate the extraction of the nociceptive tone of informations having priority over other stimuli.

Organization of the efferent projections from the spinal cervical enlargement to the parabrachial area and periaqueductal gray: a PHA-L study in the rat.

The organization of efferent projections from the spinal cervical enlargement to the parabrachial (PB) area and the periaqueductal gray (PAG) was studied in the rat by using microinjections of Phaseolus vulgaris-leucoagglutinin (PHA-L) into different laminae around the C7 level. The results demonstrated two areas of cervical enlargement which project in different ways to the PB area and PAG. First, the superficial laminae (I, II) showed a very dense projection, with a clear contralateral dominance at the coronal level where the inferior colliculus merges with the pons, to a restricted "superficial" portion of the PB area, namely the lateral crescent area, the dorsal lateral, the superior lateral (PBsl), and the outer portion of the external lateral PB subnuclei. Less dense projections were observed in the Kölliker-Fuse nucleus (KF) and in the ventrolateral/lateral quadrant of the caudal and mid PAG. By contrast, the labeling was weak or absent in the other PB subnuclei and the outer adjacent regions; in particular, no, or very little, labeling was found in the cuneiform nucleus. The PB area appeared to be the supraspinal target that received the densest projection from laminae I and II. Projections were less dense in the PAG and the thalamus and markedly less in other sites such as the ventrolateral medulla, the subnucleus reticularis dorsalis, and the nucleus of the solitary tract. Second, the reticular portion of lamina V, the medial portion of laminae IV-VI up to X and lamina VIII, showed bilateral projections with a weak ipsilateral dominance and a high to medium density on a very restricted portion of the PB area, namely the internal lateral PB subnucleus. A lesser projection was also observed in the adjacent portion of the PBsl, the KF, and the lateral quadrant of the PAG. These results suggest that signals carried by neurons from lamina I-II converge on a restricted superficial portion of the PB area and the ventral part of the lateral quadrant of the PAG. These results are discussed in the context of the role of the spino-PB and spino-PAG pathways in nociception.

Distribution of spinal cord projections from the medullary subnucleus reticularis dorsalis and the adjacent cuneate nucleus: A phaseolus vulgaris‐ leucoagglutinin study in the rat

The distribution and organization of descending spinal projections from the dorsal part of the caudal medulla were studied in the rat following injections of Phaseolus vulgaris-leucoagglutinin into small areas of the subnucleus reticularis dorsalis (SRD) and the adjacent cuneate nucleus (Cu). The caudal aspect of the Cu projected only to the dorsal horn of the ipsilateral cervical cord via the dorsal funiculus. These projections were mainly to laminae I, IV, and V. More ventrally located reticular structures projected to the full length of the cord. Fibers originating from the SRD travelled through the ipsilateral dorsolateral funiculus and terminated within the deep dorsal horn and upper layers of the ventral horn, mainly in laminae V-VII. Fibers originating from subnucleus reticularis ventralis (SRV) travelled ipsilaterally through the lateral and ventrolateral funiculi and bilaterally through the ventromedial funiculus. These fibers terminated within the ventral horn. The density of labeling within the gray matter varied at different levels of the cord was as follows: cervical > sacral > thoracic > lumbar. The reciprocal connections between the caudal medulla and the spinal cord suggest that the former is an important link in feedback loops that regulate spinal outflow.

Effects of heterotopic noxious stimuli on activity of neurones in subnucleus reticularis dorsalis in the rat medulla.

1. In anaesthetized rats, recordings were made in the medullary subnucleus reticularis dorsalis. Neurones with total nociceptive convergence (TNC) responded to percutaneous electrical stimuli with early and late peaks due to the activation of A delta and C fibres respectively, no matter which part of the body was stimulated. Neurones with partial nociceptive convergence (PNC) responded with an A delta peak regardless of which part of the body was stimulated, and with a C peak of activation from some, mainly contralateral, parts of the body. 2. All TNC neurones responded to noxious thermal stimulation of the limbs with a phasic discharge followed by tonic activity that lasted throughout the stimulation. Discharges elicited by applying stimuli simultaneously to both forepaws or to a hindpaw and a forepaw were lower than the individual responses to stimulation of a single limb. Similar negative interactions were observed in the responses of PNC neurones following noxious thermal stimulation of two paws. 3. In both neuronal populations, the simultaneous application of noxious thermal stimuli and microelectrophoretic application of D,L-homocysteic acid (DLH) induced responses of greater magnitude than those evoked by each stimulus alone. 4. TNC neurones responded to electrical stimulation of the contralateral hindpaw with A delta and C fibre responses. Noxious thermal stimuli applied to different areas of the body induced an excitatory response during the period that preceded the electrical stimulation, but an inhibition of both A delta and C fibre responses. By contrast, using a similar protocol, application of DLH induced a steady discharge in the period preceding the electrical stimulation and also in between the A delta and C fibre responses, which were not themselves inhibited. 5. The negative heterotopic influences in normal rats during simultaneous immersion of the ipsi- and contralateral hindpaws was strongly reduced in rats with bilateral lesions of the dorsolateral funiculi at the cervical level (C3-C4). 6. It is concluded that strong negative interactions elicited by heterotopic noxious stimuli are observed in the spinoreticular system. Such interactions do not occur at the subnucleus reticularis dorsalis level but are mediated by supraspinal structures which control, through the dorsolateral funiculi, the spinal transmission of nociceptive information.

Hindbrain structures involved in pain processing as revealed by the expression of c-Fos and other immediate early gene proteins

We have used the evoked expression of the immediate early gene-encoded proteins (c-Fos, Fos B, Jun B, Jun D, c-Jun and Krox-24) to monitor sensory processing in the hindbrain structures of rats undergoing somatic inflammation. Experiments were performed on freely moving animals that did not experience constraints other than those imposed by the disease itself. Local injections of chemicals were used to cause subcutaneous inflammation of the plantar foot or monoarthritis by intracapsular injection. Labelling was studied at survival times that corresponded either to the time points of maximum labelling in the spinal cord (4 h for the subcutaneous model, 24 h and two weeks for the monoarthritis model) or at survival times that corresponded to the chronic phase of monoarthritis evolution (six, nine and 15 weeks). Controls consisted of freely moving, unstimulated animals. Basal expression was observed for all immediate early genes and in a variety of stuctures, but always remained moderate. All immediate early gene-encoded protein expressions except c-Jun were evoked, but except for c-Fos, and to a lesser extent Jun D, intensities of staining always remained faint. The following results will be mainly based on c-Fos expression, as this protein proved to be the most effective marker for all the survival times studied. Somatic pain evoked c-Fos expression in a subset of discrete subrogions of both the caudal medulla oblongata and transitional areas of the pontomesencephalic junction. In the caudal medulla oblongata, structures involved were the caudal intermediate reticular nucleus, the subnucleus reticularis dorsalis, the ventrolateral reticular formation and the lateral paragigantocellular nucleus. Structures involved at the pontomesencephalic junction level mostly included the superior and dorsal lateral subnuclei of the parabrachial area, the nucleus cuneiformis and the most caudal portions of the lateral central gray, also including the laterodorsal tegmental nucleus; labelling in other lateral subnuclei of the parabrachial area always remained moderate. Staining in the caudal reticular areas was evident only at short survival times (4 and 24 h survival times in subcutaneous and monoarthritis models, respectively). Staining in nuclei of the pontomesencephalic junction was evident in all cases except for the very long survival periods (six to 15 weeks) of monoarthritis. In all cases staining was bilateral with contralateral predominance with regard to the stimulated limb. The present work demonstrates that hindbrain stuctures involved in somatic pain processing can be effectively identified in behaving animals and that c-Fos is the most reliable activity marker in this case. The structures involved only partially overlap with those implicated in anaesthesia or visceronociceptive processing as demonstrated previously, thus suggesting that a certain degree of specificity could exist for some of them. Nuclei of the caudal medulla oblongata would be more involved in eliciting cardiovascular behaviours that acute pain elicits while nuclei of the pontomesencephalic junction would be more involved in mediating pain of inflammatory origin.

Convergence of visceral and somatic inputs onto subnucleus reticularis dorsalis neurones in the rat medulla.

1. In anaesthetized rats, recordings were made within the medullary subnucleus reticularis dorsalis (SRD) from neurones that exhibited convergence of nociceptive inputs from the entire surface of the body. Neurones with total nociceptive convergence responded to supramaximal percutaneous electrical stimuli (2 ms duration) with early and late peaks due to the activation of A delta and C fibres, respectively, no matter which part of the body was stimulated. Neurones with partial nociceptive convergence responded to identical stimuli with an A delta peak of activation regardless of which part of the body was stimulated and with a C peak of activation from some, mainly contralateral, parts of the body. The characteristics of the responses of these neurones to graded colo-rectal distension (< or = 100 mmHg) were analysed. 2. The majority of neurones with total nociceptive convergence (n = 13 out of 16) responded to colo-rectal distension by increasing their firing rates. Although these neurones were virtually unresponsive to the lowest pressure employed (12.5 mmHg), they increased their discharges monotonically for distensions in the 26-100 mmHg range and these responses were sometimes followed by after-discharges. One of these neurones, which exhibited a high level of spontaneous activity, was inhibited during colo-rectal distension. None of the neurones with partial nociceptive convergence recorded (n = 10) ever changed its firing rate during increases of intracolonic pressure up to 100 mmHg. 3. It is concluded that neurones with total nociceptive convergence give monotonic stimulus-response relationships for colo-rectal distensions. Thus, neurones with total nociceptive convergence can encode the strength of visceral stimuli, probably within the noxious range, just as they have previously been shown to do for thermal and mechanical cutaneous stimuli. Together with previous electrophysiological and neuroanatomical findings, this study provides further evidence for the convergence of noxious inputs onto single SRD neurones. 4. It is suggested that neurones with total nociceptive convergence could be a link in spino-bulbospinal loops involved in autonomic reactions to strong visceral stimulation. In addition, SRD neurones could be an important supraspinal relay in the mechanisms of visceral pain.

Involvement of the subnucleus reticularis dorsalis in diffuse noxious inhibitory controls in the rat

Several lines of evidence have suggested the participation of the caudal medulla, including the subnucleus reticularis dorsalis (SRD), in the supraspinally mediated diffuse noxious inhibitory controls (DNICs). To test this hypothesis directly, DNICs acting on spinal convergent neurones were compared in sham-operated rats and rats with unilateral quinolinic acid-induced lesions of the SRD. Inhibitions produced by heterotopic noxious stimuli (i.e. DNIC), of the C-fibre-evoked responses of the convergent neurones were significantly reduced in the lesioned animals. This depression of DNIC, by 40–45%, was similar no matter where the conditioning stimuli were applied and was not significantly different for neurones recorded ipsilaterally to the lesion from those recorded contralaterally. These results suggest that the SRD is one of the supraspinal relay(s) in the circuitry underlying DNIC in the rat.

Spinal afferent projections to subnucleus reticularis dorsalis in the rat

Small amounts of the retrograde tracer WGA-apoHRP-Au complex were injected in the caudal medulla to study the spinal afferents to the subnucleus reticularis dorsalis (SRD). Labelled neurones were found at all levels of the spinal cord: the highest numbers were in the ipsilateral cervical spinal cord (mainly laminae I, V, VI, VII, VIII and X), the lowest were at the thoracic and lumbar levels bilaterally, while an intermediate density was found bilaterally at the sacral level. When injection sites were located in the underlying subnucleus reticularis ventralis (SRV), labelling was bilateral and mainly in the deep layers of the cervical spinal cord. Together with our previous electrophysiological and anatomical data, this study suggests that the SRD provides a link in spino-reticulo-spinal loops implicated in the processing of pain.

Trigeminal nociceptive neurons in the subnucleus reticularis ventralis. I. Response properties and afferent connections

Trigeminal nociceptive neurons within the subnucleus reticularis ventralis medullae oblongatae (SRV), which lies ventral to the trigeminal subnucleus caudalis and subnucleus reticularis dorsalis medullae oblongatae, were studied in urethane/chloralose-anesthetized cats and monkeys. These neurons were called ‘SRV neurons’. They were almost regularly excited by pressure to the ipsilateral cornea or to both corneas at a strength well above the human corneal pain threshold. Most of them were activated by noxious mechanical stimulation of the pinna, face and/or tongue. A significant fraction of SRV units was responsive to tapping of the ipsilateral dorsum of the nose and/or electrical stimulation of tooth pulp afferents. Evidence was obtained that responses to tapping of the dorsum of the nose were due to mechanical distortion of the nasal mucosa. Intracellular injection of HRP into SRV neurons demonstrated that injected neurons were large neurons characteristic of the SRV. Trigeminal tractotomy just rostral to the obex did not eliminate responses of SRV units to trigeminal inputs. Neurons relaying trigeminal inputs to SRV neurons were electrophysiologically identified in the nucleus reticularis parvocellularis which is ventromedially adjacent to the subnuclei oralis and interpolaris of the trigeminal spinal tract nucleus. These findings were supported by HRP injection into the SRV. Units having receptive fields similar to those of SRV neurons were found in lamina VII of the first cervical cord, suggesting that SRV neurons may be trigeminal lamina VII neurons.

Acupuncture-evoked responses of subnucleus reticularis dorsalis neurons in the rat medulla

Recordings were made from neurons in subnucleus reticularis dorsalis of the rat. Two populations of neurons could be distinguished: those with total nociceptive convergence which were driven by activating Aδ- and C-fibers from any part of the body and those with partial nociceptive convergence which were driven by activating A δ -fibers from any part of the body or C-fibers from some, mainly contralateral, regions. The effects on subnucleus reticularis dorsalis neurons of manual acupuncture, performed by a traditional Chinese acupuncturist at the “Renzhong”, “Sousanli”, “Changqiang”, and “Zusanli” acupoints and at a non-acupoint next to “Zusanli”, were studied. Acupuncture stimulation for 30 s at the acupoints or the non-acupoint strongly excited all the total nociceptive convergence neurons tested; these neurons responded with a discharge of rapid onset which was often followed by after-discharges lasting for approximately 30–60 s. The majority but not all of the partial nociceptive convergence neurons responded to 30 s of acupuncture stimulation at the acupoints or the non-acupoint. This was especially the case when the stimulus was applied to contralateral or midline parts of the body. The potency of acupuncture as a means of activating subnucleus reticularis dorsalis neurons varied significantly with the area of the body being stimulated such that: contralateral > midline > ipsilateral areas. The levels of induced activity were of similar magnitude to those evoked by noxious mechanical stimuli applied under identical experimental conditions. No differences were found between the capacities to activate subnucleus reticularis dorsalis neurons of the “Zusanli” point and the adjacent non-acupoint, no matter whether these were stimulated ipsi- or contralaterally; this suggests a lack of topographical specificity in the activation of these neurons. Since subnucleus reticularis dorsalis neurons are activated exclusively or preferentially by noxious inputs, it is concluded that the signals elicited by manual acupuncture travel through pathways responsible for the transmission of nociceptive information. Since acupuncture, a manoeuvre which is known to elicit widespread extrasegmental antinociceptive effects, activates subnucleus reticularis dorsalis neurons which, anatomically, send dense projections to the dorsal horn at all levels of the spinal cord, we would suggest that this structure may be involved not only in signalling pain but also in modulating pain by means of spino-reticulo-spinal feed-back mechanisms.

Corneal Representation within the Trigeminal Subnucleus Caudalis and Adjacent Bulbar Lateral Reticular Formation of the Cat.

Corneal units in the trigeminal subnucleus caudalis and adjacent bulbar lateral reticular formation were studied in urethane-chloralose anesthetized cats. Corneal units were categorized into four classes: low-threshold corneal (LTC) units, high-threshold corneal (HTC) units, wide dynamic range (WDR) units with corneal input, and subnucleus reticularis ventralis (SRV) units with corneal input. Corneal receptive fields of these four classes of corneal afferent units consisted of 3-6 spots. Mechanical thresholds of LTC units were lower than 30 mg (2.6 g/mm2) and were comparable to the sensory threshold of the human cornea measured in patients with cataract. Mechanical thresholds of the other 3 classes of corneal afferent units were well above the pain threshold in the human cornea. LTC units were located in the magnocellular layer of trigeminal subnucleus caudalis and were intermingled with cutaneous low-threshold mechanoreceptive units. HTC units were coexistent with nociceptive specific units in the marginal layer and in the outer zone of substantia gelatinosa. WDR units with corneal input were found in the lateral part of trigeminal lamina V equivalent, which corresponds to the lateral part of subnucleus reticularis dorsalis. These 3 classes of corneal units were found at a level 2.7-3.5 mm caudal to the obex. SRV units were found in the dorsolateral part of SRV along the entire length of the medulla oblongata caudal to the obex. These results support the suggestion that either nonpainful sensation or pain can be evoked from the cornea.

Efferent projections from the subnucleus reticularis dorsalis (SRD): A Phaseolus vulgaris leucoagglutinin study in the rat

Small iontophoretic applications of Phaseolus vulgaris leucoagglutinin (PHA-L) were used in rats to study the efferent projections from a restricted region in the reticular formation of the caudal medulla: the subnucleus reticularis dorsalis (SRD). It was found that fibres from SRD project mainly to the spinal cord, the oral motor nuclei, the dorsal accessory inferior olive, the giganto- and parvo-cellular nuclei of the reticular formation and the parafascicular and ventromedian nuclei of the thalamus. Together with our previous electrophysiological findings, this study suggests that the SRD could be involved both in the control of pain processing and in motor reactions elicited by noxious events.

Convergence of heterotopic nociceptive information onto neurons of caudal medullary reticular formation in monkey (Macaca fascicularis)

1. Recordings were made in anesthetized monkeys from neurons in the medullary reticular formation (MRF) caudal to the obex. Responses of 19 MRF neurons to mechanical, thermal, and/or electrical stimulation were examined. MRF neurons exhibited convergence of nociceptive cutaneous inputs from widespread areas of the body and face. 2. MRF neurons exhibited low levels of background activity. Background activity increased after periods of intense cutaneous mechanical or thermal stimulation. Nearly all MRF neurons tested failed to respond to heterosensory stimuli (flashes, whistle sounds), and none responded to joint movements. 3. MRF neurons were excited by and encoded the intensity of noxious mechanical stimulation. Responses to stimuli on contralateral limbs were greater than those to stimuli on ipsilateral limbs. Responses were greater to stimuli on the forelimbs than to stimuli on the hindlimbs. 4. MRF neurons responded to noxious thermal stimulation (51 degrees C) of widespread areas of the body. Mean responses from stimulation at different locations were generally parallel to those for noxious mechanical stimulation. Responses increased with intensity of noxious thermal stimulation (45-50 degrees C). 5. MRF neurons responded with one or two peaks of activation to percutaneous electrical stimulation applied to the limbs, the face, or the tail. The differences in latency of responses to stimulating two locations along the tail suggested that activity was elicited by activation of peripheral fibers with a mean conduction velocity in the A delta range. Stimulation of the contralateral hindlimb elicited greater responses, with lower thresholds and shorter latencies, than did stimulation of the ipsilateral hindlimb. 6. Electrophysiological properties of monkey MRF neurons resembled those of neurons in the medullary subnucleus reticularis dorsalis (SRD) in the rat. Neurons in the caudal medullary reticular formation could play a role in processing nociceptive information. Convergence of nociceptive cutaneous input from widespread areas of the body suggests that MRF neurons may contribute to autonomic, affective, attentional, and/or sensory-motor processes related to pain.

Ascending pathways in the spinal cord involved in the activation of subnucleus reticularis dorsalis neurons in the medulla of the rat

1. Recordings were made from neurons in the left medullary subnucleus reticularis dorsalis (SRD) of anesthetized rats. Two populations of neurons were recorded: neurons with total nociceptive convergence (TNC), which gave responses to A delta- and C-fiber activation from the entire body after percutaneous electrical stimulation, and neurons with partial nociceptive convergence (PNC), which responded to identical stimuli with an A delta-peak regardless of which part of the body was stimulated and with a C-fiber peak of activation from some, mainly contralateral, parts of the body. 2. The effects of various, acute, transverse sections of the cervical (C4-C5) spinal cord on the A delta- and C-fiber-evoked responses were investigated by building poststimulus histograms (PSHs) after 50 trials of supramaximal percutaneous electrical stimulation of the extremity of either hindpaw (2-ms duration; 3 times threshold for C-fiber responses), before and 30-40 min after making the spinal lesion. 3. In the case of TNC neurons, hemisections of the left cervical cord blocked the responses elicited from the right hindpaw and slightly, but not significantly, diminished those evoked from the left hindpaw. Conversely, hemisections of the right cervical cord abolished TNC responses elicited from the left hindpaw without significantly affecting the responses elicited from the right hindpaw. 4. Lesioning the dorsal columns or the left dorsolateral funiculus was found not to affect the TNC neuronal responses elicited from either hindpaw. By contrast, lesioning the left lateral funiculus or the most lateral part of the ventrolateral funiculus, respectively, reduced and blocked the responses elicited from the right hindpaw without affecting those evoked from the left hindpaw. 5. After lesions that included the most lateral parts of the left ventral funiculus, PNC neuronal responses elicited from the right hindpaw were also abolished, whereas those elicited from the left hindpaw remained unchanged. 6. We conclude that the signals responsible for the activation of SRD neurons travel principally in the lateral parts of the ventrolateral quadrant, a region that classically has been implicated in the transmission of noxious information. Both a crossed and a double-crossed pathway are involved in this process. The postsynaptic fibers of the dorsal columns and the spinocervical and spinomesencephalic tracts do not appear to convey signals that activate SRD neurons. 7. The findings also suggest that lamina I nociceptive specific neurons, the axons of which travel within the dorsolateral funiculus, do not contribute very much to the activation of SRD neurons.

Responses of neurones of the centralis nucleus of the amigdala to peripheral noxious stimuli

The present study was designed to investigate a role of the subnucleus reticularis dorsalis (SRD) in the analgesia produced by a low dose of naloxone during carrageenan-induced inflammation. Male Sprague–Dawley rats were divided into the following two groups: (1) rats with bilateral lesions of the SRD (n=13) and 2) sham-operated rats (n=24). In each group, effects of a low dose of naloxone (5 μg/kg, i.p.) on thermal nociception were examined 4 h, 7 and 28 days after the induction of unilateral inflammation. Carrageenan (6 mg in 0.15 ml saline) was injected subcutaneously into the plantar surface of the left hindpaw. The analgesic effect was assessed by prolongation of the paw withdrawal latency (PWL) to heating. Prior to carrageenan injection, a low dose of naloxone did not prolong PWLs in either group. Four hours after carrageenan, a low dose of naloxone produced a prolongation of PWLs in both sham-operated and SRD-lesioned rats. Seven days after carrageenan, naloxone failed to produce analgesia in the SRD-lesioned rats but did produce analgesia in the sham-operated rats. At 28 days, a low dose of naloxone induced hyperalgesia in the inflamed paw of both groups, whereas naloxone was ineffective in the contralateral non-inflamed paw. These results suggest that the SRD plays a role in naloxone-induced analgesia during the subacute phase of inflammation (e.g. 7 days after induction of inflammation).

Efferent projections from the subnucleus reticularis dorsalis (SRD) of the rat medulla studied with the PHA-L methods

Efferent projections from the subnucleus reticularis dorsalis (SRD) of the rat medulla studied with the PHA-L methods

Ascending pathways involved in the activation of subnucleus reticularis dorsalis (SRD) neurones in the rat medulla

Terminal fibers anterogradely labeld with Phaseolus vulgaris leucoagglutinin (PHA-L) were observed in the locus coeruleus in the brainstem of the cat and the cynomolgus monkey following injections in lamina I of the spinal or medullary dorsal horn. Thus, thermoreceptive- or nociceptive-specific lamina I cells that project to the locus coeruleus could directly influence arousal, vigilance, and the descending control of spinal integration.

Effects of systemic morphine upon Aδ- and C-fibre evoked activities of subnucleus reticularis dorsalis neurones in the rat medulla

The effects of intravenous administration of morphine were examined on Aδ- and C-fibre evoked activities of subnucleus reticularis dorsalis (SRD) neurones in the rat medulla. This region may have an important role in nociception since SRD neurones exhibit whole body receptive fields from which they can be activated preferentially or exclusively by noxious stimulation. The present study demonstrates that morphine can depress the C-fibre evoked responses of SRD neurones in a dose-related (3–12 mg/kg range) and naloxone reversible fashion; however the Aδ-fibre evoked responses of these neurones were depressed only with the greatest dose employed. Since a similar dose can depress by 50% the C-fibre evoked activities of SRD and spinal dorsal horn convergent neurones, it is suggested that the depressant effect of morphine on SRD neurones arises primarily from its spinal action.

Encoding of electrical, thermal, and mechanical noxious stimuli by subnucleus reticularis dorsalis neurons in the rat medulla.

1. In anesthetized rats, recordings were made within the medullary subnucleus reticularis dorsalis (SRD) from neurons that exhibited convergence of nociceptive inputs from the entire body. Neurons with total nociceptive convergence (TNC) responded to suprathreshold percutaneous electrical stimuli (2-ms duration) with an early and a late peak due to activation of A delta- and C-fibers, respectively, no matter which part of the body was stimulated. Neurons with partial nociceptive convergence (PNC) responded to the same stimuli with an A delta-peak regardless of which part of the body was stimulated and with a C-peak of activation from some, mainly contralateral, parts of the body. The characteristics of the responses of these neurons to the application of graded intensities of electrical, thermal, and mechanical stimuli were analyzed. 2. All TNC neurons and 85% of PNC neurons responded to A delta- and C-fiber activation following percutaneous electrical stimulation of the contralateral hindpaw. With regard to A delta-fiber-evoked responses, a linear relationship between the logarithm of the applied current and the magnitude of the responses was found within the 0.25- to 6.0-mA and 0.5- to 24-mA ranges for TNC and PNC neurons, respectively; however, these curves were essentially similar. With regard to C-fiber-evoked responses, such a linear relationship was found within the 1.5- to 6.0-mA range for both types of SRD neurons, although the TNC neurons presented larger C-fiber-evoked responses than did the PNC neurons. 3. TNC and PNC neurons linearly increased their discharges during the application of noxious thermal stimuli to the contralateral hindpaw within the range 44-52 degrees C; the mean responses evoked by noxious heat from TNC neurons were of higher magnitude than those from PNC neurons. The majority of SRD neurons presented long-lasting afterdischarges, especially with the highest temperature employed (52 degrees C). 4. TNC neurons monotonically increased their discharges during graded mechanical or thermal stimulation of the tail. When mechanical stimuli were applied, a linear relationship was found between the logarithm of the strength of the mechanical stimulus and the neuronal discharges, in the 5.3- to 7.4-N/cm2 range. With thermal stimulation, TNC neurons linearly increased their discharges in the 44-52 degrees C range. When increasing amounts of the tail were immersed in a 50 degrees C waterbath, TNC neurons increased their discharges within a restricted range of tail surface areas (0.9-5.7 cm2); further increases in the stimulated surface size were not followed by increases in firing rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Convergence of heterotopic nociceptive information onto subnucleus reticularis dorsalis neurons in the rat medulla.

1. In anesthetized rats recordings were made from neurons in the medulla caudal to the obex. In the medullary dorsal horn, typical trigeminal noxious specific, nonnoxious specific, and convergent neurons were found. In nucleus cuneatus, typical dorsal column units were recorded. In subnucleus reticularis dorsalis (SRD), recordings were made from neurons which exhibited convergence of nociceptive inputs from the entire body. In subnucleus reticularis ventralis (SRV) we recorded both from neurons with spontaneous activity that were either unaffected or inhibited by noxious stimuli applied to various parts of the body and from respiratory neurons. The present paper deals particularly with the nature of the stimuli that activated reticular neurons exhibiting nociceptive convergence. 2. Neurons with nociceptive convergence could be activated by mechanical, thermal, or chemical noxious stimuli applied to widespread areas of the body. By using percutaneous electrical stimulation, we found that they responded to the activation of peripheral fibers in the A delta- and C-range. Two neuronal subpopulations were defined according to the way in which SRD neurons responded to the electrical stimuli, namely: "neurons with total nociceptive convergence" (TNC) and "neurons with partial nociceptive convergence" (PNC). 3. The great majority (84%) of TNC neurons did not exhibit spontaneous activity and none of these neurons gave responses to heterosensory (flashes, whistle sounds) or proprioceptive stimuli. Most (88%) did not respond to any kind of innocuous cutaneous stimuli. By contrast, the entire population of TNC neurons responded to noxious mechanical, thermal, and visceroperitoneal stimuli. In the majority of cases (71%) long-lasting afterdischarges were observed following cessation of the application of the nociceptive stimulus. 4. All the TNC neurons responded to suprathreshold percutaneous electrical stimulation (2-ms duration) with two peaks of activation no matter which part of the body was stimulated. By stimulating two regions of the tail, 100 mm apart, we determined that the early and late peaks of activation were triggered by activities in peripheral fibers with mean conduction velocities of 10.8 +/- 0.5 and 0.74 +/- 0.05 (SE) m/s, respectively, i.e., A delta- and C-fibers. The mean thresholds for obtaining A delta-fiber components were found in the 0.4-0.7-mA range; the mean thresholds for obtaining C-fiber components were found in the 6-7.5- and 3-4-mA range for the face and the other parts of the body, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)