Intrathecal Baclofen: Effects on Spasticity, Pain, and Consciousness in Disorders of Consciousness and Locked-in Syndrome

Pistoia, Francesca; Sacco, Simona; Sarà, Marco; Franceschini, Marco; Carolei, Antonio

doi:10.1007/s11916-014-0466-8

Cited by 42 publications

(32 citation statements)

References 58 publications

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“…Intrathecal baclofen is primarily used as a centrally acting treatment for spasticity but it has been suggested as a potential drug to stimulate the recovery of consciousness in a few uncontrolled studies and case-reports. 15,28 The effects of midazolam (benzodiazepine receptor agonist) 18 and ziconitide (atypical analgesic, selective blocker of N-type calcium channels) 19 have also been reported in two single-case studies as stimulant for the recovery of consciousness of patients with prolonged DOC (one MCS and one UWS, respectively). 18,19 These anecdotal findings need to be confirmed with controlled studies.…”

Section: Intrathecal Baclofen and Other Drugsmentioning

confidence: 99%

Therapeutic interventions in patients with prolonged disorders of consciousness

Thibaut

Schiff

Giacino

et al. 2019

The Lancet Neurology

262

229

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The management of patients with severe brain injuries and prolonged disorders of consciousness (DOC) raises important issues particularly with respect to their therapeutic options. The lack of treatment is challenged by new clinical and neuroimaging data indicating that some patients with prolonged DOC may benefit from therapeutic interventions, even years after the injury. The majority of the studies aiming at improving patients' level of consciousness and functional recovery includes behavioural and brain imaging open-label trials and case-reports, but several randomized clinical trials (RCT) have been conducted, especially using non-invasive brain stimulation. Only a couple of RCTs focused on the effects of drugs or sensory stimulation approaches, and only two Class II studies, on amantadine and transcranial direct current stimulation, have been published. While new therapeutic approaches seem to be valuable for patients with prolonged DOC, optimized stimulation parameters, alternative drugs or rehabilitation strategies still need to be tested and validated.

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Section: Intrathecal Baclofen and Other Drugsmentioning

confidence: 99%

Therapeutic interventions in patients with prolonged disorders of consciousness

Thibaut

Schiff

Giacino

et al. 2019

The Lancet Neurology

262

229

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“…Substance P receptor was found most commonly in the alveus of the hippocampus, an area of GABAergic neurons commonly associated with inhibition of pain and epileptiform activity. 49–51 …”

Section: Methodsmentioning

confidence: 99%

Honokiol for the Treatment of Neonatal Pain and Prevention of Consequent Neurobehavioral Disorders

Woodbury

Chen

et al. 2015

J. Nat. Prod.

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This study examined the short- and long-term neuroprotective and analgesic activity of honokiol (a naturally occurring lignan isolated from Magnolia) on developing brains in neonates exposed to inflammatory pain, known to cause neuronal cell death. Postnatal day 4 (P4) neonatal rat pups were subjected to intraplantar formalin injection to four paws as a model of severe neonatal pain. Intraperitoneal honokiol (10 mg/kg) or corn oil vehicle control was administered 1 h prior to formalin insult, and animals were maintained on honokiol through postnatal day 21 (P21). Behavioral tests for stress and pain were performed after the painful insult, followed by morphological examinations of the brain sections at P7 and P21. Honokiol significantly attenuated acute pain responses 30 min following formalin insult and decreased chronic thermal hyperalgesia later in life. Honokiol-treated rats performed better on tests of exploratory behavior and performed significantly better in tests of memory. Honokiol treatment normalized hippocampal and thalamic c-Fos and hippocampal alveus substance P receptor expression relative to controls at P21. Together, these findings support that (1) neonatal pain experiences predispose rats to the development of chronic behavioral changes and (2) honokiol prevents and reduces both acute and chronic pathological pain-induced deteriorations in neonatal rats.

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“…This may include identifying possibilities for therapies using neuromodulation, with neuroimaging being used also in the monitoring of changes in time within the same patient and evaluating the effectiveness of treatment strategies [25,66,67]. Some therapeutic approaches have in fact been reported to speed the recovery of consciousness in subgroups of patients in UWS/VS or MCS [68,69,70,71,72,73,74,75,76]. These approaches include the use of pharmacological agents, such as zolpidem, levodopa, dopamine agonists and intrathecal baclofen as well as non-pharmacological therapies including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation and spinal cord stimulation [68,69,70,71,72,73,74,75,76].…”

Section: Emerging Neuroimaging Evidence About the Experience Of Pamentioning

confidence: 99%

Disorders of Consciousness: Painless or Painful Conditions?—Evidence from Neuroimaging Studies

et al. 2016

Self Cite

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The experience of pain in disorders of consciousness is still debated. Neuroimaging studies, using functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET), multichannel electroencephalography (EEG) and laser-evoked potentials, suggest that the perception of pain increases with the level of consciousness. Brain activation in response to noxious stimuli has been observed in patients with unresponsive wakefulness syndrome (UWS), which is also referred to as a vegetative state (VS), as well as those in a minimally conscious state (MCS). However, all of these techniques suggest that pain-related brain activation patterns of patients in MCS more closely resemble those of healthy subjects. This is further supported by fMRI findings showing a much greater functional connectivity within the structures of the so-called pain matrix in MCS as compared to UWS/VS patients. Nonetheless, when interpreting the results, a distinction is necessary between autonomic responses to potentially harmful stimuli and conscious experience of the unpleasantness of pain. Even more so if we consider that the degree of residual functioning and cortical connectivity necessary for the somatosensory, affective and cognitive-evaluative components of pain processing are not yet clear. Although procedurally challenging, the particular value of the aforementioned techniques in the assessment of pain in disorders of consciousness has been clearly demonstrated. The study of pain-related brain activation and functioning can contribute to a better understanding of the networks underlying pain perception while addressing clinical and ethical questions concerning patient care. Further development of technology and methods should aim to increase the availability of neuroimaging, objective assessment of functional connectivity and analysis at the level of individual cases as well as group comparisons. This will enable neuroimaging to truly become a clinical tool to reliably investigate pain in severely brain-injured patients as well as an asset for research.

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Intrathecal Baclofen: Effects on Spasticity, Pain, and Consciousness in Disorders of Consciousness and Locked-in Syndrome

Cited by 42 publications

References 58 publications

Therapeutic interventions in patients with prolonged disorders of consciousness

Therapeutic interventions in patients with prolonged disorders of consciousness

Honokiol for the Treatment of Neonatal Pain and Prevention of Consequent Neurobehavioral Disorders

Disorders of Consciousness: Painless or Painful Conditions?—Evidence from Neuroimaging Studies

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