Subnucleus Reticularis Dorsalis Neurons Research Articles

Electroacupuncture Inhibits Visceral Nociception via Somatovisceral Interaction at Subnucleus Reticularis Dorsalis Neurons in the Rat Medulla.

Electroacupuncture (EA) is an efficacious treatment for alleviating visceral pain, but the underlining mechanisms are not fully understood. This study investigated the role of medullary subnucleus reticularis dorsalis (SRD) neurons in the effects of EA on visceral pain. We recorded the discharges of SRD neurons extracellularly by glass micropipettes on anesthetized rats. The responses characteristics of SRD neurons to different intensities of EA (0.5, 1, 2, 4, 6, and 8 mA, 0.5 ms, and 2 Hz) on acupoints “Zusanli” (ST 36) and “Shangjuxu” (ST 37) before and during noxious colorectal distension (CRD) were analyzed. Our results indicated that SRD neurons responded to either a noxious EA stimulation ranging from 2 to 8 mA or to noxious CRD at 30 and 60 mmHg by increasing their discharge frequency at an intensity-dependent manner. However, during the stimulation of both CRD and EA, the increasing discharges of SRD neurons induced by CRD were significantly inhibited by 2–8 mA of EA. Furthermore, SRD neurons can encode the strength of EA, where a positive correlation between current intensity and the magnitude of neuronal responses to EA was observed within 2–6 mA. Yet, the responses of SRD neurons to EA stimulation reached a plateau when EA exceeded 6 mA. In addition, 0.5–1 mA of EA had no effect on CRD-induced nociceptive responses of SRD neurons. In conclusion, EA produced an inhibiting effect on visceral nociception in an intensity-dependent manner, which probably is due to the somatovisceral interaction at SRD neurons.

Medulla Oblongata Mechanism of Inhibitory Effect of Thermal Stimulation to Nociceptive Colorectal Distention in Rats

Objective: To discuss mechanism of moxibustion (thermal stimulation) effect and best moxibustion stimulus parameter. Methods: Experiments were performed on 48 male Sprague-Dawley rats. Unit discharges from individual single neuron were recorded extracellularly with glass-microelectrode in Subnucleus Reticularis Dorsalis (SRD). Visceral-intrusive stimulation is done by colorectal distension. Thermal stimulation with different temperature (40°C, 42°C, 44°C, 46°C, 48°C, 50°C, 52°C) and different stimulus area (diameter of circle : 1.0 cm, 1.5 cm, 2.0 cm, 2.5 cm, 3.0 cm, 3.5 cm, 4.0cm) was applied around RN12 during nociceptive colorectal distension. Results: SRD neurons could be activated by visceral stimulation within noxious range. Under low temperature of stimulus, especially under 45°C of pain threshold to ordinary people, visceral nociceptive afferent facilitated thermal stimulus from the body surface. While after thermal stimulation reached a harmful degree, the thermal stimulus will inhibit visceral nociceptive afferent. Moreover, statistics show that the higher the temperature is, the smaller the size of stimulation area is needed, and they correlate with each other negatively. Conclusion: Visceral nociception could be inhibited by somatic thermal stimulation with specific parameter at medulla level. According to our finding, best thermal stimulation temperature is around 48°C and the best size of stimulation area is around 3.14-7.07cm2 (with 2.0-3.0cm diameter).

Changes in responses of neurons in spinal and medullary subnucleus reticularis dorsalis to acupoint stimulation in rats with visceral hyperalgesia.

The purpose of this study was to explore the mechanism of acupoints sensitization phenomenon at the spinal and medulla levels. Experiments were performed on adult male Sprague-Dawley rats and visceral noxious stimuli was generated by colorectal distension (CRD). The activities of wide dynamic range (WDR) and subnucleus reticularis dorsalis (SRD) neurons were recorded. The changes of the reactions of WDR and SRD neurons to electroacupuncture (EA) on acupoints of “Zusanli-Shangjuxu” before and after CRD stimulation were observed. The results showed that visceral nociception could facilitate the response of neurons to acupoints stimulation. In spinal dorsal horn, EA-induced activation of WDR neurons further increased to 106.84 ± 17.33% (1.5 mA) (P < 0.001) and 42.27 ± 13.10% (6 mA) (P < 0.01) compared to the neuronal responses before CRD. In medulla oblongata, EA-induced activation of SRD neurons further increased to 63.28 ± 15.96% (1.5 mA) (P < 0.001) and 25.02 ± 7.47% (6 mA) (P < 0.01) compared to that before CRD. Taken together, these data suggest that the viscerosomatic convergence-facilitation effect of WDR and SRD neurons may underlie the mechanism of acupoints sensitization. But the sensitizing effect of visceral nociception on WDR neurons is stronger than that on SRD neurons.

Processing noxious information at the subnucleus reticularis dorsalis (SRD) of anesthetized cats: Wind-up mechanisms

With the exception of one monkey’s study, where wind-up was not reported, electrophysiological data from SRD neurons were obtained in rodents where they show wind-up. This work was designed to examine the response properties of SRD neurons in anesthetized cats to study how general the data from rats may be. Since cat’s SRD cells showed wind-up, its underlying mechanisms were approached, an issue not previously addressed at supraspinal level. Electrical stimulation, extracellular (combined with microiontophoresis) and intracellular techniques revealed that Aδ information reaches the SRD via the ventrolateral cord, whereas C information preferentially follows a dorsal route. Wind-up was usually generated by spinal and peripheral stimulation, but it was also evoked either by stimulating the nucleus reticularis gigantocellularis (NRGc), even after spinal cord section and bilateral full thickness removal of the cerebral cortex, or by applying microiontophoretic pulses of l-glutamate at 0.3–1 Hz. Wind-up relied on afferent repetitive activity gradually depolarizing the SRD neurons leading 3–4.5 Hz subthreshold membrane rhythmic activity to threshold. Riluzole retarded wind-up generation and decreased the number of spikes per stimulus during wind-up. GABA or glycine abolished spontaneous and sensory-evoked activity and bicuculline, but not strychnine, increased spontaneous and stimulus-evoked activity. These results demonstrate that wind-up at the SRD is not merely the reflection of spinal wind-up, but (i) can be locally generated, (ii) is partially dependent upon persistent sodium currents, and (iii) is under the modulation of a tonic GABAa-dependent inhibition decreasing SRD excitability. Injury and/or inflammation producing tonic C-fiber activation will surpass tonic inhibition generating wind-up.

The integrative role of the rat medullary subnucleus reticularis dorsalis in nociception.

Neurons within the medullary subnucleus reticularis dorsalis (SRD) of the rat convey selectively nociceptive information from all parts of the body. We have sought to define the neuronal networks that convey information from widespread noxious stimuli to the diffuse thalamocortical system and also modulate spinal outflow. The experiments, which were performed in rats, were designed to determine whether efferents from the SRD issue collaterals to the thalamus and spinal cord. Injections of the tracers fluorogold and tetramethylrhodamine-labelled dextran were centred stereotaxically in two areas that receive dense projections from the SRD: the cervical spinal cord and the lateral ventromedial thalamus (VMl), respectively. In other experimental series, SRD neurons were characterized electrophysiologically and individually labelled in a Golgi-like manner following juxtacellular iontophoresis of biotin-dextran. More than half reticulothalamic neurons within the SRD provided monosynaptic connections to the spinal cord. SRD neurons that responded to Adelta- or Adelta- and C-fibre activation from any area of the body had axons that gave both ascending and descending collaterals. Because the SRD innervates several areas involved in motor processing and receives strong, direct influences from several cortical regions, it could provide a structural basis for the processing of nociceptive and motor activities.

Spatial encoding properties of subnucleus reticularis dorsalis neurons in the rat medulla

The effect of spatial summation, produced by noxious thermal stimuli, was investigated on medullary Subnucleus Reticularis Dorsalis (SRD) neurons of anaesthetized rats. Neurons with ‘whole body’ receptive fields were excited by a random sequence of thermal stimuli involving four different surface areas of a hindpaw (1.9, 4.8, 7.5 and 18 cm 2). The responses of SRD neurons progressively decrease when the area of noxious stimulation exceeded 4.8 cm 2. The shape of the stimulus–response curve closely match the shape of dorsal horn convergent neurons, previously recorded under similar experimental conditions. These results suggest that, with respect to spatial encoding properties, SRD neurons are driven by the same supraspinally-mediated inhibitory mechanisms as dorsal horn convergent neurons.

Organization of cortical projections to the medullary subnucleus reticularis dorsalis: A retrograde and anterograde tracing study in the rat

The distribution and organization of cortical projections to the subnucleus reticularis dorsalis (SRD), the neighboring cuneate nucleus (Cu), and trigeminal nucleus caudalis (Sp5C) were studied in the rat using microinjections of wheat germ agglutinin-apo horseradish peroxidase-gold and Biotin-Dextran. Cortical cells projecting to the caudal medulla were confined to the contralateral layer V with their descending axons crossing the midline at the level of pyramidal decussation. Cortical afferents to Sp5C originated from cells located mainly in the primary somatosensory cortex (S1) and the insular cortex, whereas cortical projections to the Cu originated mainly from the primary motor cortex (M1), the primary and secondary somatosensory cortex (S1 and S2). The SRD received dense cortical afferents from larger, widespread cortical areas: M1, M2, S1, S2, and the insular cortex. The existence of dense cortico-SRD connections supports the possibility of a pyramidal influence over SRD neurons, which might modify nociceptive information ascending to the cortex itself. This proposal is consistent with the fact that SRD efferents terminate densely in thalamic areas that influence sensorimotor cortical regions which in turn project to the SRD. Moreover, these corticofugal mechanisms could allow the cortex to select its own input by suppressing or augmenting transmission of signals through SRD-hindbrain/forebrain pathways or by coordinating activities in spino-SRD-spinal circuits and thus selecting the relevant information produced by the noxious stimulus.

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.

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.

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)