A hallmark feature of chronic pain is its ability to impact other sensory and affective experiences. It is notably associated with hypersensitivity at the site of tissue injury. It is less clear, however, if chronic pain can also induce a generalized site-nonspecific enhancement in the aversive response to nociceptive inputs. Here, we showed that chronic pain in one limb in rats increased the aversive response to acute pain stimuli in the opposite limb, as assessed by conditioned place aversion. Interestingly, neural activities in the anterior cingulate cortex (ACC) correlated with noxious intensities, and optogenetic modulation of ACC neurons showed bidirectional control of the aversive response to acute pain. Chronic pain, however, altered acute pain intensity representation in the ACC to increase the aversive response to noxious stimuli at anatomically unrelated sites. Thus, chronic pain can disrupt cortical circuitry to enhance the aversive experience in a generalized anatomically nonspecific manner.DOI: http://dx.doi.org/10.7554/eLife.25302.001

Recent discoveries of striatal GABAergic interneurons require a new conceptualization of the organization of intrastriatal circuitry and their cortical and thalamic inputs. We investigated thalamic inputs to the two populations of striatal neuropeptide Y (NPY) interneurons, plateau low threshold spike (PLTS) and NPY-neurogliaform (NGF) cells. Optogenetic activation of parafascicular inputs evokes suprathreshold monosynaptic glutamatergic excitation in NGF interneurons and a disynaptic, nicotinic excitation through cholinergic interneurons. In contrast, the predominant response of PLTS interneurons is a disynaptic inhibition dependent on thalamic activation of striatal tyrosine hydroxylase interneurons (THINs). In contrast, THINs do not innervate NGF or fast spiking interneurons, showing significant specificity in THINs outputs. Chemospecific ablation of THINs impairs prepulse inhibition of the acoustic startle response suggesting an important behavioural role of this disynaptic pathway. Our findings demonstrate that the impact of the parafascicular nucleus on striatal activity and some related behaviour critically depend on synaptic interactions within interneuronal circuits.

Background: Vitamin B12 deficiency is believed to be widespread in Indian population. However, more data is needed to fuel a meaningful debate on preventive and therapeutic strategies. Aims and Objectives: Objective of the current study is to evaluate status of vitamin B12 levels in people from a tier 3 city and among people living in an urban area with or without diabetes. Settings and Design: Retrospective, cross-sectional study. Methodology: Data captured in electronic medical records (EMR) of an endocrine practice and from a diagnostic laboratory was analysed. Statistical Analysis Used: Statistical analysis was done using open source software “Jamovi”. Results: Prevalence of vitamin B12 deficiency (Vitamin B12 levels <200 pg/ml) in tier 3 city was 47.19% ( n = 267). From an urban endocrine practice, database of 11913 patients was searched for reports of vitamin B12 levels. Prevalence of vitamin B12 deficiency was 37.76% in people with pre-diabetes ( n = 92), 31.23% in people with endocrine problems other than diabetes and pre-diabetes ( n = 285) and 18.25% in people with diabetes ( n = 378). Tier 3 city population had significantly lower vitamin B12 levels than people living in an urban area and attending an endocrine clinic. Vitamin B12 levels were significantly higher in people with diabetes as compared to people with other endocrine problems. Conclusion: Prevalence of vitamin B12 deficiency is 47% in north Indian population. People with diabetes have higher vitamin B12 levels than general population though still have high prevalence of deficiency. This data shows that Vitamin B12 deficiency is widespread in Indian population.

Pain is a complex sensory and affective experience. The current definition for pain relies on verbal reports in clinical settings and behavioral assays in animal models. These definitions can be subjective and do not take into consideration signals in the neural system. Local field potentials (LFPs) represent summed electrical currents from multiple neurons in a defined brain area. Although single neuronal spike activity has been shown to modulate the acute pain, it is not yet clear how ensemble activities in the form of LFPs can be used to decode the precise timing and intensity of pain. The anterior cingulate cortex (ACC) is known to play a role in the affective-aversive component of pain in human and animal studies. Few studies, however, have examined how neural activities in the ACC can be used to interpret or predict acute noxious inputs. Here, we recorded in vivo extracellular activity in the ACC from freely behaving rats after stimulus with non-noxious, low-intensity noxious, and high-intensity noxious stimuli, both in the absence and chronic pain. Using a supervised machine learning classifier with selected LFP features, we predicted the intensity and the onset of acute nociceptive signals with high degree of precision. These results suggest the potential to use LFPs to decode acute pain.