Cortical excitability in tramadol dependent patients: A transcranial magnetic stimulation study

Khedr, Eman M.; Gabra, Romany H.; Noaman, Mostafa M.; El-Fetoh, Noha Abo; Farghaly, Hanan S.M.

doi:10.1016/j.drugalcdep.2016.09.027

Cited by 10 publications

(5 citation statements)

References 48 publications

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“…Finally, the patients' maintenance medications (e.g., selective serotonin and norepinephrine reuptake inhibitor antidepressants (SSNRI) and analgesics) were not discontinued during the study. There are reports that analgesics (e.g., Tramadol) affects cortical excitability [67]. At the same time, serotogenic and adrenergic drugs were shown to modulate plasticity induced by other brain stimulation techniques such as transcranial direct current stimulation (tDCS) and paired associative stimulation (PAS) [68,69].…”

Section: Discussionmentioning

confidence: 99%

Comparing the Impact of Multi-Session Left Dorsolateral Prefrontal and Primary Motor Cortex Neuronavigated Repetitive Transcranial Magnetic Stimulation (nrTMS) on Chronic Pain Patients

et al. 2021

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Repetitive transcranial stimulation (rTMS) has been shown to produce an analgesic effect and therefore has a potential for treating chronic refractory pain. However, previous studies used various stimulation parameters (including cortical targets), and the best stimulation protocol is not yet identified. The present study investigated the effects of multi-session 20 Hz (2000 pulses) and 5 Hz (1800 pulses) rTMS stimulation of left motor cortex (M1-group) and left dorsolateral prefrontal cortex (DLPFC-group), respectively. The M1-group (n = 9) and DLPFC-group (n = 7) completed 13 sessions of neuronavigated stimulation, while a Sham-group (n = 8) completed seven sessions of placebo stimulation. The outcome was measured using the German Pain Questionnaire (GPQ), Depression, Anxiety and Stress Scale (DASS), and SF-12 questionnaire. Pain perception significantly decreased in the DLPFC-group (38.17%) compared to the M1-group (56.11%) (p ≤ 0.001) on the later sessions. Health-related quality of life also improved in the DLPFC-group (40.47) compared to the Sham-group (35.06) (p = 0.016), and mental composite summary (p = 0.001) in the DLPFC-group (49.12) compared to M1-group (39.46). Stimulation of the left DLPFC resulted in pain relief, while M1 stimulation was not effective. Nonetheless, further studies are needed to identify optimal cortical target sites and stimulation parameters.

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Section: Discussionmentioning

confidence: 99%

Comparing the Impact of Multi-Session Left Dorsolateral Prefrontal and Primary Motor Cortex Neuronavigated Repetitive Transcranial Magnetic Stimulation (nrTMS) on Chronic Pain Patients

et al. 2021

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“…Early indications of a central mechanism of action came from a study that demonstrated prevention of thermal hindpaw hyperalgesia (with no altered nociception) upon intraperitoneal application of low dose tramadol [56]. A supraspinal mechanism of action is postulated since human imaging studies have demonstrated enhanced reward system activation upon tramadol consumption [57] while dependency is shown to hyperexcite the motor cortex coupled with inhibitory deficits [58].…”

Section: Supraspinal Sites Of Action: Pain Modulationmentioning

confidence: 99%

Central Nervous System Targets: Supraspinal Mechanisms of Analgesia

Bannister

Dickenson

2020

Neurotherapeutics

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While the acute sensation of pain is protective, signaling the presence of actual or potential bodily harm, its persistence is unpleasant. When pain becomes chronic, it has limited evolutionarily advantage. Despite the differing nature of acute and chronic pain, a common theme is that sufferers seek pain relief. The possibility to medicate pain types as varied as a toothache or postsurgical pain reflects the diverse range of mechanism(s) by which pain-relieving “analgesic” therapies may reduce, eliminate, or prevent pain. Systemic application of an analgesic able to cross the blood–brain barrier can result in pain modulation via interaction with targets at different sites in the central nervous system. A so-called supraspinal mechanism of action indicates manipulation of a brain-defined circuitry. Pre-clinical studies demonstrate that, according to the brain circuitry targeted, varying therapeutic pain-relieving effects may be observed that relate to an impact on, for example, sensory and/or affective qualities of pain. In many cases, this translates to the clinic. Regardless of the brain circuitry manipulated, modulation of brain processing often directly impacts multiple aspects of nociceptive transmission, including spinal neuronal signaling. Consideration of supraspinal mechanisms of analgesia and ensuing pain relief must take into account nonbrain-mediated effects; therefore, in this review, the supraspinally mediated analgesic actions of opioidergic, anti-convulsant, and anti-depressant drugs are discussed. The persistence of poor treatment outcomes and/or side effect profiles of currently used analgesics highlight the need for the development of novel therapeutics or more precise use of available agents. Fully uncovering the complex biology of nociception, as well as currently used analgesic mechanism(s) and site(s) of action, will expedite this process.

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“…The mean patients' AIMS score was 12.4 + 2.9 ranging from 5 to 17 points. RMT, AMT, I/O, cSP and iSP were evaluated as previously reported by Khedr et al [8,9,10,11]. Any trials in which there was detectable pre-stimulus EMG activity were discarded from the analysis on the basis that this indicated that the participants were not completely relaxed.…”

Section: Educationmentioning

confidence: 99%

Changes in recruitment of motor cortex excitation and inhibition in patients with drug-induced tardive syndromes

Khedr

Fawal

Abdel-Warith

et al. 2019

Neurophysiologie Clinique

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Objectives: It has recently been suggested that drug induced Tardive Syndromes (TS) might be due to maladaptive plasticity which increases motor excitability in cerebral cortex and basal ganglia. In order to test this hypothesis we performed the first measurements of cortical excitability in TS. Methods: Motor cortex excitability was examined using transcranial magnetic stimulation (TMS) in 22 TS patients and compared with that in 20 age and sex-matched healthy individuals. Resting and active motor threshold (RMT, AMT) and input-output curves (I/O curves) assessed corticospinal excitability. The duration of the contralateral silent period (cSP) at a range of stimulation intensities and ipsilateral silent period (iSP) were used as measures of inhibition.Results: There were no significant differences in RMT and AMT between patients and controls, although the input-output curves were significantly steeper in patients. The cSP (at different stimulus intensities) and iSP were both longer in the patients compared to the control group. But most of this difference could be accounted for by increased recruitment of motor evoked potentials (MEPs) in patients. Conclusion:TS is characterized by hyperexcitability of corticospinal output that might contribute to the lack of selectivity in muscle recruitment and contribute to excess involuntary movement. The findings are opposite to those in naturally-occurring hyperkinesia such as Sydenham's and Huntington's chorea suggesting a fundamental difference in the pathophysiology.

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Cortical excitability in tramadol dependent patients: A transcranial magnetic stimulation study

Cited by 10 publications

References 48 publications

Comparing the Impact of Multi-Session Left Dorsolateral Prefrontal and Primary Motor Cortex Neuronavigated Repetitive Transcranial Magnetic Stimulation (nrTMS) on Chronic Pain Patients

Comparing the Impact of Multi-Session Left Dorsolateral Prefrontal and Primary Motor Cortex Neuronavigated Repetitive Transcranial Magnetic Stimulation (nrTMS) on Chronic Pain Patients

Central Nervous System Targets: Supraspinal Mechanisms of Analgesia

Changes in recruitment of motor cortex excitation and inhibition in patients with drug-induced tardive syndromes

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