Inhibition of primate spinothalamic tract neurons by stimulation in ventral posterior lateral (VPLc) thalamic nucleus: possible mechanisms

Gerhart, K. D.; Yezierski, Robert P.; Fang, Zheng; Willis, W. D.

doi:10.1152/jn.1983.49.2.406

Cited by 121 publications

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“…Tsubokawa et al 17 observed that VB stimulation is effective in inhibiting abnormal hyperactivity in the medullary dorsal horn of cats submitted to retrogasserian rhizotomy and that such inhibition is resistant to naloxone. Gerhart et al 7 demonstrated that unilateral VB stimulation inhibits the activity of dorsal horn nociceptive neurons, bilaterally, as well as their responses to both noxious and innocuous stimuli (Fig 1). They also showed that these effects could be abolished by a lesion in the spinal cord including both bilateral DLF and the ventral part of the ipsilateral lateral funiculus.…”

Section: Commentsmentioning

confidence: 96%

“…However, no significant change in LCGU was detected in the spinal dorsal horn, nucleus raphe magnus and nucleus raphe dorsalis. Gerhart et al 7 demonstrated that, in monkeys, the latency for VB stimulation induced inhibition of dorsal horn neurons in the lumbosacral enlargement is 33.7 ms. Willis et al 19 , working with monkeys also, showed that the latency for VB stimulation excitation of RVM neurons is 35.6 ms and that the latency for antidromic activation of RVM neurons by stimulation of the DLF in an upper lumbar level is 8.2 ms. One can easily see, contrarily to what would be expected from Tsubokawa's hypothesis, that the latency for inhibition of dorsal horn neurons by VB stimulation is less than the sum of the latencies for VB stimulation excitation of RVM neurons and DLF stimulation antidromic excitation of RVM neurons.…”

Section: Commentsmentioning

confidence: 99%

“…Tsubokawa et al 1 5 , 1 7 , 1 8 proposed that VB stimulation produces pain relief by excitation of the rostroventral medulla (RVM), which, in turn, projects inhibitory descending axons through both dorsolateral funiculi (DLF) of the spinal cord to the dorsal horn nociceptive neurons (Fig 1). Gerhart et al 7 demonstrated that such inhibition is abolished by a spinal cord lesion including both bilateral DLF and the ventral part of the ipsilateral lateral funiculus. Based on these observations, one could expect that unilateral VB stimulation would produce bilateral pain relief, VB and periventricularperiaqueductal gray (PVG-PAG) stimulation would be useful for treating the same modalities of pain (the pathway involved in DH nociceptive neurons inhibition by PVG-PAG stimulation is the same as that proposed for VB stimulation) and that in patients with complete cord transection presenting with central cord-based pain, VB stimulation would not work at all.…”

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Pathways involved in thalamic ventrobasal stimulation for pain relief: evidence against the hypothesis VB stimulation -> rostroventral medulla excitation -> dorsal horn inhibition

Filho

Tasker

1994

Arq. Neuro-Psiquiatr.

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SUMMARY -Despite its use for a long time, the way thalamic ventrobasal (VB) stimulation acts to produce pain relief is still unknown. One of the most accepted hypotheses, sponsored by Tsubokawa among others, proposes that VB stimulation excites raphespinal and reticulospinal neurons of the rostroventral medulla which in turn send respectively inhibitory serotonergic and noradrenergic axons through both dorsolateral funiculi (DLF) to the dorsal horn ( DH) nociceptive neurons; this pathway would be the same as is involved in periventricular-periaqueductal gray (PVG-PAG) stimulation induced inhibition of DH nociceptive neurons. This hypothesis implicates the necessity of DLF intactness; in fact, it was showed that section of bilateral DLF inhibits the response of DH nociceptive neurons to VB stimulation. If the above mentioned hypothesis is correct, one could expect that unilateral VB stimulation would produce bilateral pain relief, VB and PVG stimulation would be useful for treating the same modalities of pain and that in patients with central cord-based pain harboring complete cord transection, VB stimulation would not work at all. In order to check these possibilities, the patiens with central cord-based pain admitted to the Division of Neurosurgery, Toronto Hospital between June 1978 and July 1991 to undergo deep brain stimulation (DBS) were reviewed. Sixteen patients were operated on. Based on clinical criteria, four out of these sixteen patients were thought to present complet cord transection (all four were men, with an average age of 48 years and pain secondary to cord injury). The effectiveness of the procedure was evaluated in this subset of patients: 75% of them enjoyed excellent pain relief with VB stimulation; PVG stimulation, however, performed in three out of these four patients, did not produce pain relief. Besides, our clinical experience has demonstrated that VB stimulation is effective in treating only contralateral pain.These results, as well as certain experimental data provided by a review of the literature, seem to provide evidence enough to contest Tsubokawa's hypothesis.KEY WORDS: pain, analgesia, electrical stimulation therapy, thalamic nuclei, thalamus, stereotaxis. V i a s e n v o l v i d a s n o a l í v i o d a d o r p e l a e s t i m u l a ç ã o t a l â m i c a v e n t r o b a s a l : e v i d ê n c i a c o n t r a a h i p ó t e s e e s t i m u l a ç ã o v e n t r o b a s a l -> e x c i t a ç ã o d o b u l b o r o s t r o v e n t r a l -> i n i b i ç ã o d o c o r n o d o r s a lRESUMO -A despeito de seu uso há longo tempo, a maneira pela qual a estimulação talâmica ventrobasal (VB) produz alívio da dor é ainda desconhecida. Segundo uma das hipóteses mais aceitas, defendida por Tsubokawa dentre outros, a estimulação de VB excita neurônios rafe-espinhais e reticulo-espinhais do bulbo rostroventral, os quais por sua vez emitem respectivamente axônios serotoninérgicos e noradrenérgicos inibitórios para os neurônios nociceptivos de ambos os cornos dorsais através dos funículos dorsolaterais...

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Section: Commentsmentioning

confidence: 96%

Section: Commentsmentioning

confidence: 99%

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confidence: 99%

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Pathways involved in thalamic ventrobasal stimulation for pain relief: evidence against the hypothesis VB stimulation -> rostroventral medulla excitation -> dorsal horn inhibition

Filho

Tasker

1994

Arq. Neuro-Psiquiatr.

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“…Gerhart et al (1983) reported that stimulation of the ventral posterior lateral thalamus nucleus could inhibit spinothalamic tract neurons in anesthetized monkeys. The response of spinothalamic tract neurons to electrical stimulation of A and C fibers in the sural nerve were reduced during thalamic stimulation.…”

Section: Painmentioning

confidence: 99%

Brain Stimulation for Neurological and Psychiatric Disorders, Current Status and Future Direction

Chang¹

2004

J Pharmacol Exp Ther

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Interest in brain stimulation therapies has been rejuvenated over the last decade and brain stimulation therapy has become an alternative treatment for many neurological and psychiatric disorders, including Parkinson's disease (PD), dystonia, pain, epilepsy, depression, and schizophrenia. The effects of brain stimulation on PD are well described, and this treatment has been widely used for such conditions worldwide. Treatments for other conditions are still in experimental stages and large-scale, well controlled studies are needed to refine the treatment procedures. In the treatment of intractable brain disorders, brain stimulation, especially transcranial magnetic stimulation (TMS), is an attractive alternative to surgical lesioning as it is relatively safe, reversible, and flexible. Brain stimulation, delivered either via deeply implanted electrodes or from a surface-mounted transcranial magnetic device, can alter abnormal neural circuits underlying brain disorders. The neural mechanisms mediating the beneficial effects of brain stimulation, however, are poorly understood. Conflicting theories and experimental data have been presented. It seems that the action of stimulation on brain circuitry is not limited to simple excitation or inhibition. Alterations of neural firing patterns and long-term effects on neurotransmitter and receptor systems may also play important roles in the therapeutic effects of brain stimulation. Future research on both the basic and clinical fronts will deepen our understanding of how brain stimulation works. Realtime computation of neural activity allows for integration of brain stimulation signals into ongoing neural processing. In this way abnormal circuit activity can be adjusted by optimal therapeutic brain stimulation paradigms.The modern era of brain stimulation treatment started in the 1950s with an early application of deep brain stimulation (DBS) to treat patients with intractable pain. Interest in DBS as a treatment for movement disorders has surged since the late 1980s. With the development of new devices such as transcranial magnetic stimulators and refinements in DBS paradigms, brain stimulation has been gradually replacing surgical ablation as a uniquely promising clinical procedure for the treatment of many neurological disorders that are unresponsive to existing therapies. Movement DisordersParkinson's Disease. Although pharmacological dopamine (DA) enhancement has therapeutic benefits for PD, long-term use also produces the undesirable side effect of dyskinesia. Surgical ablation and DBS were explored during the 1970s and 1980s. Benabid et al. (1987) reported that high-frequency stimulation of the ventral intermediate thalamic nucleus can suppress the tremor syndrome of PD. During the following decade, we witnessed tremendous interest and great success of DBS treatments in PD.Currently, the major targets of DBS for PD treatment are the subthalamic nucleus (STN) and the internal segment of globus pallidus (GPi) within the thalamocortical basal ganglia pathways....

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“…There is also experimental evidence against this hypothesis: A) Aiko et al 2 demonstrated increase in local glucose utilization in SI, but not in the DH, following VB stimulation, B) SI stimulation inhibits preferentially DH nociceptive neurons responses to innocuous stimuli while VB stimulation has no preferential effect, although DH nociceptive cells responses to C fiber volleys are reduced to a greater extent than their responses to A fiber volleys 11,30 , C) SI stimulation ipsilateral to an spinothalamic tract neuron produces only weak inhibitory effects, while ipsilateral VB stimulation usually causes a powerful inhibition 11 and D) Inhibition of the responses of spinothalamic cells to noxious stimuli following VB stimulation is observed even when SI stimulation fails to inhibit the responses of the same cells to such stimuli 11 .…”

Section: Vb Stimulation Produces Pain Relief By Antidromic Activationmentioning

confidence: 99%

Thalamic ventrobasal stimulation for pain relief: probable mechanisms, pathways and neurotransmitters

Filho¹

1994

Arq. Neuro-Psiquiatr.

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SUMMARY -Thalamic ventrobasal (VB) stimulation, first performed by Mazars, in 1961, is a valuable means for treating central and deafferentation pain. The way it acts to achieve pain relief, however, is still a matter of controversy. In this paper, the author examines previously proposed hypotheses and suggests that VB stimulation induces pain relief by activation of a multisynaptyic inhibitory pathway to the medial thalamus, in which the dopaminergic nigrostriatal system exerts an important role and by modulation of abnormal activity in VB itself. The multisynaptic pathway involved, as well as the neurotransmitters, are suggested: VB stimulation excites somatosensory cortex through the glutaminergic thalamocortical pathway, which in turn, sends excitatory glutaminergic axons to the motor cortex. The sensorymotor cortex originates the excitatory glutaminergic corticostriatal pathway to the anterior putamen. The anterior putamen sends excitatory peptidergic (substance P) pathways to the globus pallidus interims (striatopallidal pathway) and to the substantia nigra reticulata (striatonigral pathway). The globus pallidus interims inhibits the medial thalamus through the pallidothalamic GABAergic pathway. The substantia nigra reticulata sends inhibitory GABAergic projections to the medial thalamus (nigrothalamic pathway) and excites the substantia nigra compacta. The substantia nigra compacta projects excitatory dopaminergic axons to the striatal neurons (nigrostriatal pathway) with output to the globus pallidus internus and substantia nigra reticulata and so on. Data to support this hypothesis are provided by an extensive review of the literature.KEY WORDS: pain, analgesia, electrical stimulation, thalamic nuclei, thalamus, cerebral cortex, basal ganglia, neurotransmitters. Estimulação talâmica ventrobasal para alívio da dor: prováveis mecanismos, vias e neurotransmissoresRESUMO -A estimulação talâmica ventrobasal (VB), primeiramente realizada por Mazars em 1961, é método útil para o tratamento de dor central e dor de deaferentação. A maneira como ela atua para produzir alívio da dor, porém, é ainda questão de controvérsia. Neste estudo, o autor examina as hipóteses anteriormente propostas e sugere que o alívio da dor obtido pela estimulação de VB se deve a dois prováveis mecanismos: (1) Modulação da atividade anormal em VB e (2) Ativação de uma via multisináptica inibitória para os neurônios nociceptives do tálamo medial, na qual o sistema dopaminérgico nigroestriatal exerce importante papel. A via multisináptica envolvida, bem como os neurotransmissores, são sugeridos: a estimulação de VB, através da via tálamo-cortical glutaminérgica, excitaria o córtex somatosensitivo que, por sua vez, excitaria o córtex motor através dos neurotransmissores excitatórios glutamato e aspartate. No córtex sensitivo-motor se originaria a via corticoestriatal glutaminérgica excitatória para o putâmen anterior, o qual emitiria uma via peptidérgica (substância P) excitatória para o globo pálido interno (via estriatopalidal) e para a s...

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Inhibition of primate spinothalamic tract neurons by stimulation in ventral posterior lateral (VPLc) thalamic nucleus: possible mechanisms

Cited by 121 publications

References 0 publications

Pathways involved in thalamic ventrobasal stimulation for pain relief: evidence against the hypothesis VB stimulation -> rostroventral medulla excitation -> dorsal horn inhibition

Pathways involved in thalamic ventrobasal stimulation for pain relief: evidence against the hypothesis VB stimulation -> rostroventral medulla excitation -> dorsal horn inhibition

Brain Stimulation for Neurological and Psychiatric Disorders, Current Status and Future Direction

Thalamic ventrobasal stimulation for pain relief: probable mechanisms, pathways and neurotransmitters

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