Evidence for increased motor cortical facilitation and decreased inhibition in atypical depression.

OBJECTIVE: Major depressive disorder (MDD) is a clinically heterogeneous condition. However, the role of cortical glutamate and gamma-aminobutyric acid (GABA) receptor-mediated activity, implicated in MDD pathophysiology, has not been explored in different MDD subtypes. Our aim was to assess the atypical and melancholic depression subtypes regarding potential differences in GABA and glutamate receptor-mediated activity through established transcranial magnetic stimulation (TMS) neurophysiological measures from the motor cortex. METHOD: We evaluated 81 subjects free of antidepressant medication, including 21 healthy controls and 20 patients with atypical, 20 with melancholic, and 20 with undifferentiated MDD. Single and paired-pulse TMS paradigms were used to evaluate intracortical facilitation (ICF), cortical silent period (CSP), and short intracortical inhibition (SICI), which index glutamate, GABAB receptor-, and GABAA receptor-mediated activity respectively. RESULTS: Patients with MDD demonstrated significantly decreased mean CSP values than healthy controls (Cohen's d = 0.22-0.3, P < 0.01 for all comparisons). Atypical depression presented a distinct cortical excitability pattern of decreased cortical inhibition and increased cortical facilitation, that is, an increased mean ICF and SICI ratios than other depression subtypes (d = 0.22-0.33, P < 0.01 for all comparisons). CONCLUSION: Different MDD subtypes may demonstrate different neurophysiology in relation to GABAA and glutamatergic activity. TMS as an investigational tool might be useful to distinguish between different MDD subtypes.

Beyond weakness: Characterization of pain, sensory profile and conditioned pain modulation in patients with motor neuron disease: A controlled study.

BACKGROUND: Motor neuron diseases (MND) represent a group of disorders that evolve with inexorable muscle weakness and medical management is based on symptom control. However, deeper characterization of non-motor symptoms in these patients have been rarely reported. METHODS: This cross-sectional study aimed to describe non-motor symptoms in MND and their impact on quality of life and functional status, with a focus on pain and sensory changes. Eighty patients (31 females, 55.7 ± 12.9 years old) with MND underwent a neurological examination, pain, mood, catastrophizing and psychophysics assessments [quantitative sensory testing (QST) and conditioned pain modulation (CPM)], and were compared to sex- and age-matched healthy controls (HC). RESULTS: Chronic pain was present in 46% of patients (VAS =5.18 ± 2.0). Pain of musculoskeletal origin occurred in 40.5% and was mainly located in the head/neck (51%) and lower back (35%). Neuropathic pain was not present in this sample. Compared to HC, MND patients had a lower cold detection threshold (p < 0.002), and significantly lower CPM scores (4.9 ± 0.2% vs. 22.1 ± 0.2%, p = 0.012). QST/CPM results did not differ between MND patients with and without pain. Pain intensity was statistically correlated with anxiety, depression and catastrophism, and spasticity scores were inversely correlated with CPM (ρ = -0.30, p = 0.026). CONCLUSIONS: Pain is frequently reported by patients with MNDs. Somatosensory and CPM changes exist in MNDs and may be related to the neurodegenerative nature of the disease. Further studies should investigate the most appropriate treatment strategies for these patients. SIGNIFICANCE: We report a comprehensive evaluation of pain and sensory abnormalities in motor neuron disease (MND) patients. We assessed the different pain syndromes present in MND with validated tools, and described the QST and conditioned pain modulation profiles in a controlled design.

Sensory abnormalities and pain in Parkinson disease and its modulation by treatment of motor symptoms.

Pain and sensory abnormalities are present in a large proportion of Parkinson disease (PD) patients and have a significant negative impact in quality of life. It remains undetermined whether pain occurs secondary to motor impairment and to which extent it can be relieved by improvement of motor symptoms. The aim of this review was to examine the current knowledge on the mechanisms behind sensory changes and pain in PD and to assess the modulatory effects of motor treatment on these sensory abnormalities. A comprehensive literature search was performed. We selected studies investigating sensory changes and pain in PD and the effects of levodopa administration and deep brain stimulation (DBS) on these symptoms. PD patients have altered sensory and pain thresholds in the off-medication state. Both levodopa and DBS improve motor symptoms (i.e.: bradykinesia, tremor) and change sensory abnormalities towards normal levels. However, there is no direct correlation between sensory/pain changes and motor improvement, suggesting that motor and non-motor symptoms do not necessarily share the same mechanisms. Whether dopamine and DBS have a real antinociceptive effect or simply a modulatory effect in pain perception remain uncertain. These data may provide useful insights into a mechanism-based approach to pain in PD, pointing out the role of the dopaminergic system in pain perception and the importance of the characterization of different pain syndromes related to PD before specific treatment can be instituted.

Into the island: a new technique of non-invasive cortical stimulation of the insula.

STUDY AIM: We describe a new neuronavigation-guided technique to target the posterior-superior insula (PSI) using a cooled-double-cone coil for deep cortical stimulation. INTRODUCTION: Despite the analgesic effects brought about by repetitive transcranial magnetic stimulation (TMS) to the primary motor and prefrontal cortices, a significant proportion of patients remain symptomatic. This encouraged the search for new targets that may provide stronger pain relief. There is growing evidence that the posterior insula is implicated in the integration of painful stimuli in different pain syndromes and in homeostatic thermal integration. METHODS: The primary motor cortex representation of the lower leg was used to calculate the motor threshold and thus, estimate the intensity of PSI stimulation. RESULTS: Seven healthy volunteers were stimulated at 10 Hz to the right PSI and showed subjective changes in cold perception. The technique was safe and well tolerated. CONCLUSIONS: The right posterior-superior insula is worth being considered in future studies as a possible target for rTMS stimulation in chronic pain patients.

The assessment and management of pain in the demented and non-demented elderly patient / Avaliação e manejo da dor em pacientes idosos com e sem demência

Persistent pain is a frequent health problem in the elderly. Its prevalence ranges from 45 percent to 80 percent. Chronic diseases, such as depression, cardiovascular disease, cancer and osteoporosis have a higher prevalence in aged individuals and increase the risk of developing chronic pain. The presence of pain is known to be associated with sleep disorders in these patients, as well as functional impairment, decreased sociability and greater use of the health system, with consequent increase in costs. Alzheimer's disease patients seem to have a normal pain discriminative capacity and they may probably have weaker emotional and affective experience of pain when compared to other types of dementia. Many patients have language deficits and thus cannot properly describe its characteristics. In more advanced cases, it becomes even difficult to determine whether pain is present or not. Therefore, the evaluation of these patients should be performed in a systematic way. There are three ways to measure the presence of pain: by direct questioning (self-report), by direct behavioral observation and by interviews with caregivers or informants. In recent years, many pain scales and questionnaires have been published and validated specifically for the elderly population. Some are specific to patients with cognitive decline, allowing pain evaluation to be conducted in a structured and reproducible way. The next step is to determine the type of painful syndrome and discuss the bases of the pharmacological management, the use of multiple medications and the presence of comorbidities demand the use of smaller doses and impose contra-indications against some drug classes. A multiprofessional approach is the rule in the management of these patients.

Dor persistente é um problema de saúde frequente no idoso e sua prevalência varia de 45 a 80 por cento. Doenças crônicas, como depressão, distúrbios cardiovasculares, câncer e osteoporose tem alta prevalência em indivíduos idosos e aumentam o risco de desenvolver dor crônica. Nestes indivíduos, a presença de dor está associada a distúrbios do sono, prejuízo funcional, diminuição da sociabilidade e maior procura dos serviços de saúde, com o consequente aumento dos custos de saúde. Pacientes com Alzheimer têm uma capacidade discriminativa dolorosa normal e uma experiência afetiva e emocional da dor mais atenuada quando comparados com outros tipos de demência. Muitos pacientes têm déficits de linguagem e não podem descrever adequadamente as características de sua dor. Em casos avançados, torna-se difícil determinar se a dor está realmente presente ou não. Desta forma, a avaliação destes doentes deve ser realizada de forma sistemática. Há três formas de se avaliar a dor: questionários diretos, observação direta do comportamento ou entrevistas diretas com os cuidadores ou informantes. Nos últimos anos muitas escalas e questionários para dor foram publicados e validados especificamente para a população idosa. Alguns são específicos para pacientes com declínio cognitivo, permitindo que a evolução da dor possa ser conduzida de uma forma estruturada e reprodutível. O passo seguinte é se determinar o tipo de síndrome dolorosa e se discutir as bases do manejo farmacológico. O uso de múltiplas medicações e a presença de comorbidades exige o uso de pequenas doses e impõem contra-indicações para algumas classes de drogas. A abordagem multidisciplinar é a regra no seguimento a longo prazo destes doentes.