Articles: neuralgia.
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Pharmacol Res Perspect · Oct 2018
Randomized Controlled TrialTolerability, pharmacokinetics, and pharmacodynamics of mirogabalin in healthy subjects: Results from phase 1 studies.
Three phase 1 pharmacokinetic (PK)/pharmacodynamics (PD) studies were conducted in healthy men and women to further characterize the safety, tolerability, and PK/PD of mirogabalin administration with or without food and to guide the dose selection and regimen for phase 2 and 3 clinical development. The 3 studies included 2 randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose studies, and 1 open-label, crossover study to evaluate the PK of mirogabalin administered under fasting and fed (high-fat meal) conditions. Forty-eight and 47 healthy volunteers completed the single- and multiple-dose studies, respectively. ⋯ No significant accumulation occurred with multiple doses over 14 days. After single doses of mirogabalin (15 mg), the bioavailability was considered equivalent in the fed and fasted states, indicating that mirogabalin can be taken without food restrictions. Based on these data, mirogabalin 15 mg twice daily was selected as the highest target dose for further clinical development.
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Preclinical research for neuropathic pain has depended primarily on the use of behavioural nociceptive testing that is sensory-discriminatory-based and reflexive in nature. This can be particularly problematic in spinal cord injury (SCI)-associated neuropathic pain research where hyperreflexia may develop thus confounding interpretation of reflexive responses as pain symptoms. To address this, we have designed an affective-motivational-based Overground System that has interchangeable floors to allow examination of nociceptive behaviours in response to mechanical and cold stimuli prior to and following spinal cord injury. ⋯ We have designed an Overground System that is easy to establish and addresses a major concern in preclinical pain research by providing a cognitive- and motivational-based system for hypersensitivity detection. The affective-motivational-based Overground System allows examination of pain-like behaviours in response to cold (thermal) and rough (mechanical) stimulation prior to and following spinal cord injury. This system provides a more holistic and comprehensive assessment of nociceptive responses following SCI and helps overcome concerns of hyperreflexia confounding-evoked behavioural outcome measures in SCI models. Further, the incorporation of cognitive and motivational components brings preclinical research closer to replicating the clinical experience of a patient's motivation to participate in rewarding lifestyle activities in relation to their pain.
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There is no standardized approach to the greater occipital nerve (GON) block technique for treating occipital neuralgia. The aim of the present study was to validate the previously-suggested guidelines for conventional injection techniques and to provide navigational guidelines for safe GON block. The GON, lesser occipital nerve (LON) and occipital artery (OA) were carefully dissected in the occipital region of embalmed cadavers. ⋯ The safe injection points on the EOP-MP line are about 3 cm from the EOP, 1 cm inferior parallel to the EOP-MP line, and about 3 cm away from the MP. Clin. Anat. 31:1058-1064, 2018. © 2018 Wiley Periodicals, Inc.
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The endocannabinoid system (ECS) controls a large number of vital functions. Suboptimal tone of the ECS in certain regions of the nervous system may be associated with disorders that are also associated with pain. Pain and inflammation processes can be modulated by the exogenous supply of cannabinoids. ⋯ The "Cannabis-als-Medizin-Gesetz" (cannabis as medicine law) allows the prescription of cannabis preparations under certain conditions. Available data indicate good long-term efficacy and tolerability. However, there is little systematic long-term experience from clinical studies.
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Early hyperexcitability activity of injured nerve/neuron is critical for developing sympathetic nerve sprouting within dorsal root ganglia (DRG) since lacosamide (LCM), an anticonvulsant, inhibits Na+ channel. The present study tried to test the potential effect of LCM on inhibiting sympathetic sprouting in vivo. ⋯ Early LCM administration inhibited sympathetic sprouting within DRG in CCD rats via reducing hyperexcitability of neurons. Early LCM administration suppressed neuropathic pain in CCD rats.