An open-label, non-randomized comparison of venlafaxine and gabapentin as monotherapy or adjuvant therapy in the management of neuropathic pain in patients with peripheral neuropathy

Although many therapies are used in the management of neuropathic pain (NeP) due to polyneuropathy (PN), few comparison studies exist. We performed a prospective, non-randomized, unblended, efficacy comparison of the serotonin-norepinephrine reuptake inhibitor venlafaxine, as either monotherapy or adjuvant therapy, with a first-line medication for NeP, gabapentin, in patients with PN-related NeP. VAS pain scores were assessed after 3 and 6 months in intervention groups and in a cohort of patients receiving no pharmacotherapy. In a total of 223 patients, we analyzed pain quantity and quality (visual analogue scale [VAS] score, Brief Pain Inventory [BPI]), quality of life and health status measures [EuroQol 5 Domains, EQ-5D], Medical Outcomes Sleep Study Scale [MOSSS], Hospital Anxiety and Depression Scale [HADS] and Short Form 36 Health Survey [SF-36]) after 6 months of therapy. Significant improvements in VAS pain scores occurred for all treatment groups after 6 months. Improvements in aspects of daily life and anxiety were identified in all treatment groups. Our data suggest that monotherapy or adjuvant therapy with venlafaxine is comparable to gabapentin for NeP management. We advocate for head-to-head, randomized, double-blinded studies of current NeP therapies

Comparison of central versus peripheral delivery of pregabalin in neuropathic pain states

<p>Abstract</p> <p>Background</p> <p>Although pregabalin therapy is beneficial for neuropathic pain (NeP) by targeting the CaVα₂δ-1 subunit, its site of action is uncertain. Direct targeting of the central nervous system may be beneficial for the avoidance of systemic side effects.</p> <p>Results</p> <p>We used intranasal, intrathecal, and near-nerve chamber forms of delivery of varying concentrations of pregabalin or saline delivered over 14 days in rat models of experimental diabetic peripheral neuropathy and spinal nerve ligation. As well, radiolabelled pregabalin was administered to determine localization with different deliveries. We evaluated tactile allodynia and thermal hyperalgesia at multiple time points, and then analyzed harvested nervous system tissues for molecular and immunohistochemical changes in CaVα₂δ-1 protein expression. Both intrathecal and intranasal pregabalin administration at high concentrations relieved NeP behaviors, while near-nerve pregabalin delivery had no effect. NeP was associated with upregulation of CACNA2D1 mRNA and CaVα₂δ-1 protein within peripheral nerve, dorsal root ganglia (DRG), and dorsal spinal cord, but not brain. Pregabalin's effect was limited to suppression of CaVα₂δ-1 protein (but not CACNA2D1 mRNA) expression at the spinal dorsal horn in neuropathic pain states. Dorsal root ligation prevented CaVα₂δ-1 protein trafficking anterograde from the dorsal root ganglia to the dorsal horn after neuropathic pain initiation.</p> <p>Conclusions</p> <p>Either intranasal or intrathecal pregabalin relieves neuropathic pain behaviours, perhaps due to pregabalin's effect upon anterograde CaVα₂δ-1 protein trafficking from the DRG to the dorsal horn. Intranasal delivery of agents such as pregabalin may be an attractive alternative to systemic therapy for management of neuropathic pain states.</p

Retraction notice to "Differential impact of diabetes and hypertension in the brain: Adverse effects in grey matter" [Neurobiol. Dis., 44 (2011) 161–173, http://dx.doi.org/10.1016/j.nbd.2011.06.005]

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Why conservation biology can benefit from sensory ecology

Global expansion of human activities is associated with the introduction of novel stimuli, such as anthropogenic noise, artificial lights and chemical agents. Progress in documenting the ecological effects of sensory pollutants is weakened by sparse knowledge of the mechanisms underlying these effects. This severely limits our capacity to devise mitigation measures. Here, we integrate knowledge of animal sensory ecology, physiology and life history to articulate three perceptual mechanisms—masking, distracting and misleading—that clearly explain how and why anthropogenic sensory pollutants impact organisms. We then link these three mechanisms to ecological consequences and discuss their implications for conservation. We argue that this framework can reveal the presence of ‘sensory danger zones’, hotspots of conservation concern where sensory pollutants overlap in space and time with an organism’s activity, and foster development of strategic interventions to mitigate the impact of sensory pollutants. Future research that applies this framework will provide critical insight to preserve the natural sensory world

Ndel1 Promotes Axon Regeneration via Intermediate Filaments

Failure of axons to regenerate following acute or chronic neuronal injury is attributed to both the inhibitory glial environment and deficient intrinsic ability to re-grow. However, the underlying mechanisms of the latter remain unclear. In this study, we have investigated the role of the mammalian homologue of aspergillus nidulans NudE, Ndel1, emergently viewed as an integrator of the cytoskeleton, in axon regeneration. Ndel1 was synthesized de novo and upregulated in crushed and transected sciatic nerve axons, and, upon injury, was strongly associated with neuronal form of the intermediate filament (IF) Vimentin while dissociating from the mature neuronal IF (Neurofilament) light chain NF-L. Consistent with a role for Ndel1 in the conditioning lesion-induced neurite outgrowth of Dorsal Root Ganglion (DRG) neurons, the long lasting in vivo formation of the neuronal Ndel1/Vimentin complex was associated with robust axon regeneration. Furthermore, local silencing of Ndel1 in transected axons by siRNA severely reduced the extent of regeneration in vivo. Thus, Ndel1 promotes axonal regeneration; activating this endogenous repair mechanism may enhance neuroregeneration during acute and chronic axonal degeneration

The high-output singing displays of a lekking bat encode information on body size and individual identity

A growing body of research suggests that songs are an important part of the courtship behavior of many bat species, however there is little information on the basic characteristics of these vocalizations, or how they may function as a courtship signal. Lekking male lesser short-tailed bats (Mystacina tuberculata) appear to use vocal displays as a primary method for attracting mates, but it is unclear if these vocalizations constitute songs, and what characteristics females may use for mate selection. We recorded 16 lekking males and described the frequency and temporal properties of their vocalizations. We identified four notes (upsweeps, downsweeps, trills, and tones) that comprise courtship vocalizations, and males produced these notes either singly, or combined them linearly to form composite syllables. We classified 51 distinct syllable types (with an average of 29 types per male), with four (trills, upsweep-trills, trill-downsweeps, and upsweep-trill-downsweeps) comprising 69% of all syllables produced. The duration of trill-downsweeps scaled negatively with forearm length (a proxy for body size in bats), and all four main syllable types showed evidence of individuality. Based on the behavioral characteristics and contexts of these courtship vocalizations, we posit that this behavior constitutes singing. Furthermore, M. tuberculata potentially has one of the highest sustained song outputs yet described. Our results suggest the singing displays of M. tuberculata are signals that provide useful, honest cues of male characteristics and identity to females, and are as complex as the songs of many passerines