Recordings From Brain Stem Neurons Responding to Chemical Stimulation of the Subarachnoid Space

1997 ◽  
Vol 77 (6) ◽  
pp. 3122-3133 ◽  
Author(s):  
A. Ebersberger ◽  
M. Ringkamp ◽  
P. W. Reeh ◽  
H. O. Handwerker

Ebersberger, A., M. Ringkamp, P. W. Reeh, and H. O. Handwerker. Recordings from brain stem neurons responding to chemical stimulation of the subarachnoid space. J. Neurophysiol. 77: 3122–3133, 1997. The subarachnoid space at the base of the skull was perfused continuously with artificial cerebrospinal fluid in anesthetized rats. A combination of inflammatory mediators consisting of histamine, bradykinin, serotonin, and prostaglandin E2 (10−5 M) at pH of 6.1 was introduced into the flow for defined periods to stimulate meningeal primary afferents. Secondary neurons in the caudal nucleus of the trigeminal brain stem were searched by electrical stimulation of the cornea. Of the units receiving oligosynaptic input from the cornea, 44% were excited by stimulation of the meninges with inflammatory mediators. Most of these units had small receptive fields including cornea and the periorbital region, and their responsiveness was restricted to stimuli of noxiuos intensity. Three types of responses to stimulation of the meninges with algogenic agents were encountered: responses that did not outlast the stimulus period, responses outlasting the stimulus period for several minutes, and oscillating response patterns containing periods of enhanced and suppressed activity. The response pattern of a unit was reproducible, however, upon repetitive stimulation at 20-min intervals; the response magnitude showed tachyphylaxis upon stimulus repetition. The preparation presented mimics pathophysiolocial states normally accompanied by headache, e.g., subarachnoidal bleeding. Responsiveness of neurons in the caudal nucleus of the trigeminal brain stem to inflammatory mediators may play a role in the generation and maintenance of headache, e.g., migraine.

1998 ◽  
Vol 79 (2) ◽  
pp. 964-982 ◽  
Author(s):  
Rami Burstein ◽  
Hiroyoshi Yamamura ◽  
Amy Malick ◽  
Andrew M. Strassman

Burstein, Rami, Hiroyoshi Yamamura, Amy Malick, and Andrew M. Strassman. Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J. Neurophysiol. 79: 964–982, 1998. Chemical activation and sensitization of trigeminal primary afferent neurons innervating the intracranial meninges have been postulated as possible causes of certain headaches. This sensitization, however, cannot explain the extracranial hypersensitivity that often accompanies headache. The goal of this study was to test the hypothesis that chemical activation and sensitization of meningeal sensory neurons can lead to activation and sensitization of central trigeminal neurons that receive convergent input from the dura and skin. This hypothesis was investigated by recording changes in the responsiveness of 23 [16 wide-dynamic range (WDR), 5 high threshold (HT), and 2 low threshold (LT)] dura-sensitive neurons in nucleus caudalis to mechanical stimulation of their dural receptive fields and to mechanical and thermal stimulation of their cutaneous receptive fields after local application of inflammatory mediators or acidic agents to the dura. Responses to brief chemical stimulation were recorded in 70% of the neurons; most were short, lasting the duration of the stimulus only. Twenty minutes after chemical stimulation of the dura, the following changes occurred: 1) 95% of the neurons showed significant increases in sensitivity to mechanical indentation of the dura: their thresholds to dural indentation changed from 1.57 to 0.49 g (means, P < 0.0001), and the response magnitude to identical stimuli increased by two- to fourfold; 2) 80% of the neurons showed significant increases in cutaneous mechanosensitivity: their responses to brush and pressure increased 2.5- ( P < 0.05) and 1.6-fold ( P < 0.05), respectively; 3) 75% of the neurons showed a significant increase in cutaneous thermosensitivity: their thresholds to slow heating of the skin changed from 43.7 ± 0.7 to 40.3 ± 0.7°C ( P < 0.005) and to slow cooling from 23.7 ± 3.3 to 29.2 ± 1.8°C ( P < 0.05); 4) dural receptive fields expanded within 30 min and cutaneous receptive fields within 2–4 h; and 5) ongoing activity developed in WDR and HT but not in LT neurons. Application of lidocaine to the dura abolished the response to dural stimulation but had minimal effect on the increased responses to cutaneous stimulation (suggesting involvement of a central mechanism in maintaining the sensitized state). Antidromic activation (current of <30 μA) of dura-sensitive neurons revealed projections to the hypothalamus, thalamus, and midbrain. These findings suggest that chemical activation and sensitization of dura-sensitive peripheral nociceptors could lead to enhanced responses in central neurons and that this central sensitization therefore could result in extracranial tenderness (mechanical and thermal allodynia) in the absence of extracranial pathology. The projection targets of these neurons suggest a possible role in mediating the autonomic, endocrine, and affective symptoms that accompany headaches.


2005 ◽  
Vol 289 (4) ◽  
pp. R1107-R1115 ◽  
Author(s):  
Y. Ootsuka ◽  
R. M. McAllen

Anatomical studies indicate that sympathetic preganglionic neurons receive inputs from several brain stem cell groups, but the functional significance of this organization for vasomotor control is not known. We studied the roles of two brain stem premotor cell groups, the medullary raphé and the rostral ventrolateral medulla (RVLM), in determining the activity of sympathetic vasomotor supply to the tail of urethane-anesthetized, artificially ventilated rats. Chemical inactivation of either RVLM (bilaterally) or raphé cells by microinjecting glycine (120–200 nl, 0.5 M) or muscimol (40–160 nl, 2.1–8 mM) was sufficient to inhibit ongoing tail sympathetic fiber activity and to block its normally strong response to mild cooling via the trunk skin (reducing rectal temperature from 38.5 to 37°C). After bilateral RVLM inactivation, tail sympathetic fibers could still be excited by chemical stimulation of raphé neurons (l-glutamate, 120 nl, 50 mM), and strong cooling (rectal temperature ∼33°C) caused a low level of ongoing activity. After chemical inhibition of raphé neurons, however, neither strong cooling nor chemical stimulation of RVLM neurons activated tail sympathetic fibers. Electrical stimulation of the RVLM elicited tail sympathetic fiber volleys before and after local anesthesia of the raphé (150–500 nl of 5% tetracaine), demonstrating the existence of an independent descending excitatory pathway from the RVLM. The data show that neurons in both the medullary raphé and the RVLM, acting together, provide the essential drive to support vasomotor tone to the tail. Inputs from these two premotor nuclei interact in a mutually facilitatory manner to determine tonic, and cold-induced, tail sympathetic activity.


2003 ◽  
Vol 148 (2) ◽  
pp. 211-218 ◽  
Author(s):  
Y. Boucher ◽  
C. Simons ◽  
J. Cuellar ◽  
S.-W. Jung ◽  
M. Carstens ◽  
...  

Cephalalgia ◽  
2016 ◽  
Vol 36 (9) ◽  
pp. 875-886 ◽  
Author(s):  
XiChun Zhang ◽  
Andrew M Strassman ◽  
Victor Novack ◽  
Mitchell F Brin ◽  
Rami Burstein

Background Administration of onabotulinumtoxinA (BoNT-A) to peripheral tissues outside the calvaria reduces the number of days chronic migraine patients experience headache. Because the headache phase of a migraine attack, especially those preceded by aura, is thought to involve activation of meningeal nociceptors by endogenous stimuli such as changes in intracranial pressure (i.e. mechanical) or chemical irritants that appear in the meninges as a result of a yet-to-be-discovered sequence of molecular/cellular events triggered by the aura, we sought to determine whether extracranial injections of BoNT-A alter the chemosensitivity of meningeal nociceptors to stimulation of their intracranial receptive fields. Material and methods Using electrophysiological techniques, we identified 161 C- and 135 Aδ-meningeal nociceptors in rats and determined their mechanical response threshold and responsiveness to chemical stimulation of their dural receptive fields with TRPV1 and TRPA1 agonists seven days after BoNT-A administration to different extracranial sites. Two paradigms were compared: distribution of 5 U BoNT-A to the lambdoid and sagittal sutures alone, and 1.25 U to the sutures and 3.75 U to the temporalis and trapezius muscles. Results Seven days after it was administered to tissues outside the calvaria, BoNT-A inhibited responses of C-type meningeal nociceptors to stimulation of their intracranial dural receptive fields with the TRPV1 agonist capsaicin and the TRPA1 agonist mustard oil. BoNT-A inhibition of responses to capsaicin was more effective when the entire dose was injected along the suture lines than when it was injected into muscles and sutures. As in our previous study, BoNT-A had no effect on non-noxious mechanosensitivity of C-fibers or on responsiveness of Aδ-fibers to mechanical and chemical stimulation. Discussion This study demonstrates that extracranial administration of BoNT-A suppresses meningeal nociceptors’ responses to stimulation of their intracranial dural receptive fields with capsaicin and mustard oil. The findings suggest that surface expression of TRPV1 and TRPA1 channels in dural nerve endings of meningeal nociceptors is reduced seven days after extracranial administration of BoNT-A. In the context of chronic migraine, reduced sensitivity to molecules that activate meningeal nociceptors through the TRPV1 and TRPA1 channels can be important for BoNT-A’s ability to act as a prophylactic.


1983 ◽  
Vol 276 (1) ◽  
pp. 81-93 ◽  
Author(s):  
Robert M. Bradley ◽  
Hazel M. Stedman ◽  
Charlotte M. Mistretta

1986 ◽  
Vol 56 (5) ◽  
pp. 1411-1423 ◽  
Author(s):  
J. E. Tattersall ◽  
F. Cervero ◽  
B. M. Lumb

Single-unit electrical activity has been recorded from 95 viscerosomatic neurons in the T9 and T11 segments of the cat's spinal cord. These neurons were excited by electrical and/or natural stimulation of visceral and somatic afferent fibers. The excitatory and inhibitory effects on these neurons of volleys in somatic and visceral afferent fibers and of electrical and chemical stimulation of the nucleus raphe magnus (NRM) and adjacent areas of the reticular formation (Ret. F.) have been studied. Electrical stimulation of the splanchnic nerve produced, after the initial excitation of the neurons, a period of inhibition lasting for up to 1 s. This inhibition reduced the responsiveness of the neurons to all inputs, somatic and visceral, and was still present after spinalization of the animals with cold block, which indicates a segmental organization of the inhibition. Electrical stimulation of afferent fibers within the somatic receptive field of the neurons produced, after the initial excitation, a period of inhibition similar to that induced by visceral afferent volleys. During this period of inhibition all inputs to the neurons were reduced. Reversible spinalization of the animals with cold block did not abolish this inhibition. On the basis of the effects of reversible spinalization on the visceral input to viscerosomatic neurons, two types of neurons were distinguished: 1) neurons whose visceral responses increased in the spinal state (neurons under tonic descending inhibition) and 2) neurons whose visceral responses were decreased or abolished in the spinal state (neurons subject to descending excitation). Neurons under tonic descending inhibition were inhibited by electrical stimulation of locations within the NRM and Ret. F. This inhibition lasted for less than 100 ms and could be evoked at intensities of stimulation of 100 microA or less. Neurons under descending excitation were also inhibited by electrical stimulation in the NRM and Ret. F. but, in addition, the inhibition was preceded by an excitation in 75% of these neurons. Chemical stimulation with DL-homocysteic acid (DLH) of locations within the NRM and Ret. F. was used to activate cell bodies, but not axons, located in these brain stem sites. The only effect observed following injections of DLH into the NRM and Ret. F. was inhibition of viscerosomatic neurons including those with descending excitation as well as those with descending inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)


1999 ◽  
Vol 82 (6) ◽  
pp. 3149-3159 ◽  
Author(s):  
Philip L. Newland

Despite the importance of gustation, little is known of the central pathways responsible for the processing and coding of different chemical stimuli. Here I have analyzed the responses of a population of spiking local interneurons, with somata at the ventral midline of the metathoracic ganglion, during stimulation of chemo- and mechanoreceptors on the legs of locusts. Volatile acidic stimuli were used to selectively activate the chemosensory neurons. Different members of the population of local interneurons received depolarizing or hyperpolarizing inputs during chemosensory stimulation. Many of the same interneurons that received chemosensory input also received mechanosensory inputs from tactile hairs on the leg, but others received exclusively mechanosensory inputs. Chemosensory inputs occurred with a short and constant latency, typical of monosynaptic connections. The chemosensory receptive fields of the spiking local interneurons mapped the surface of a hind leg so that spatial information relating to the location of a taste receptor was preserved. The amplitude of potentials in interneurons during chemosensory stimulation varied in a graded manner along the long axis of the leg, thus creating gradients in the chemosensory receptive fields of interneurons. Some interneurons were depolarized to a greater extent by chemical stimuli applied to basiconic sensilla on distal parts of the leg, whereas others were depolarized more by chemical stimulation of more proximal sensilla.


1975 ◽  
Vol 20 (12) ◽  
pp. 923-924
Author(s):  
MADGE E. SCHEIBEL ◽  
ARNOLD B. SCHEIBEL

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