Curr Neuropharmacol
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Curr Neuropharmacol · Sep 2014
Combination of therapeutic hypothermia and other neuroprotective strategies after an ischemic cerebral insult.
Abrupt deprivation of substrates to neuronal tissue triggers a number of pathological events (the "ischemic cascade") that lead to cell death. As this is a process of delayed neuronal cell death and not an instantaneous event, several pharmacological and non-pharmacological strategies have been developed to attenuate or block this cascade. The most promising neuroprotectant so far is therapeutic hypothermia and its beneficial effects have inspired researchers to further improve its protective benefit by combining it with other neuroprotective agents. ⋯ A distinction is made between drugs interrupting only one event of the ischemic cascade from those mitigating different pathways and having multimodal effects. Also the combination of therapeutic hypothermia with hemicraniectomy, gene therapy and protein therapy is briefly discussed. Furthermore, those combinations that have been studied in a clinical setting are also reviewed.
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Pregabalin is an antagonist of voltage gated Ca2+ channels and specifically binds to alpha-2-delta subunit to produce antiepileptic and analgesic actions. It successfully alleviates the symptoms of various types of neuropathic pain and presents itself as a first line therapeutic agent with remarkable safety and efficacy. ⋯ Preclinical studies employing pregabalin in different neuropathic pain models have explored various molecular targets and the signaling systems including Ca2+ channel-mediated neurotransmitter release, activation of excitatory amino acid transporters (EAATs), potassium channels and inhibition of pathways involving inflammatory mediators. The present review summarizes the important aspects of pregabalin as analgesic in preclinical and clinical studies as well as focuses on the possible mechanisms.
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Curr Neuropharmacol · Dec 2013
"Bedside-to-Bench" Behavioral Outcomes in Animal Models of Pain: Beyond the Evaluation of Reflexes.
Despite the myriad promising new targets and candidate analgesics recently identified in preclinical pain studies, little translation to novel pain medications has been generated. The pain phenotype in humans involves complex behavioral alterations, including changes in daily living activities and psychological disturbances. These behavioral changes are not reflected by the outcome measures traditionally used in rodents for preclinical pain testing, which are based on reflexes evoked by sensory stimuli of different types (mechanical, thermal or chemical). ⋯ The aim has been to translate "bedside-to-bench" outcomes from the human pain phenotype to rodents, in order to complement traditional pain outcomes by providing a closer and more realistic measure of clinical pain in rodents. This review summarizes and discusses the most important nonstandard outcomes for pain assessment in preclinical studies. The advantages and drawbacks of these techniques are considered, and their potential impact on the validation of potential analgesics is evaluated.
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Curr Neuropharmacol · Sep 2012
Pharmacological risk factors for delirium after cardiac surgery: a review.
The objective of this review is to evaluate the literature on medications associated with delirium after cardiac surgery and potential prophylactic agents for preventing it. ⋯ These studies have shown that drugs taken perioperatively by cardiac surgery patients need to be considered in delirium risk management strategies. While medications with direct neurological actions are clearly important, this review has shown that specific cardiovascular drugs may also require attention. Future studies that are methodologically consistent are required to further validate these findings and improve their utility.
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The intensity of pain sensation exhibits marked day and night variations. Since the intensity of pain perception is low during dark hours of the night when melatonin levels are high, this hormone has been implicated as one of the prime antinociceptive substances. A number of studies have examined the antinociceptive role of melatonin in acute, inflammatory and neuropathic pain animal models. ⋯ Exogenous melatonin has been used effectively in the management of pain in medical conditions such as fibromyalgia, irritable bowel syndrome and migraine and cluster headache. Melatonin has been tried during surgical operating conditions and has been shown to enhance both preoperative and post-operative analgesia. The present review discusses the available evidence indicating that melatonin, acting through MT(1)/MT(2) melatonin receptors, plays an important role in the pathophysiological mechanism of pain.