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

Abstract

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...

Pathophysiology of the constant burning, tingling element of neuropathic pain: A new hypothesis

“…If the hypotheses proposed by Tsubokawa et al [58,59], Willis et al [74] and Gerhart et al [22] had been correct, VP-DBS should have been ineffective in all patients as well, as the mechanism of action proposed by these authors also depends on the integrity of the spinal cord (dorsolateral funiculi or dorsal column). However, this assumption was not borne out by our observations [61,62].…”

“…VP-DBS, clinically introduced by Mazars et al, has been used since the 1960's, and is indicated for treating the constant element of NPP [25,34,[52][53][54][55]58,59,61,62,[64][65][66][67]69,70]. Its activation provides relief of the contralateral pain exclusively.…”

“…They were detected in the MT of patients with NPP by Rinaldi et al and Jeanmonod et al [27,45]. According to Tasker and other authors, electrical stimulation of the MT in patients without NPP does not provoke any conscious impact; in patients with NPP, however, it can elicit contralateral pain, mimicking the patient's own pain [23,49,[51][52][53]62]. Among the MT afferents there is the reticulothalamic tract (RTT), whose stimulation in the midbrain, in patients with NPP, induces a response similar to the one produced by stimulation of the MT [39,50,52,53].…”

“…Vilela-Filho has proposed that the activation of a circuit built based on the presented evidence, which he later named prosencephalomesencephalic circuit (PMC), would be the mechanism responsible for the pain relief induced by VP-DBS [62]. The proposed PMC would work as follows: stimulation of VP (GLU/ ASP) ?…”

“…Vilela Filho, in an attempt to clarify the mechanisms involved in the pain relief produced by VP deep brain stimulation (DBS), proposed that it is due to the activation of a polysynaptic pathway, which he subsequently named as prosencephalomesencephalic circuit -PMC [62]. This circuit will be reviewed in detail afterwards.…”