An improved behavioural assay demonstrates that ultrasound vocalizations constitute a reliable indicator of chronic cancer pain and neuropathic pain

<p>Abstract</p> <p>Background</p> <p>On-going pain is one of the most debilitating symptoms associated with a variety of chronic pain disorders. An understanding of mechanisms underlying on-going pain, i.e. stimulus-independent pain has been hampered so far by a lack of behavioural parameters which enable studying it in experimental animals. Ultrasound vocalizations (USVs) have been proposed to correlate with pain evoked by an acute activation of nociceptors. However, literature on the utility of USVs as an indicator of chronic pain is very controversial. A majority of these inconsistencies arise from parameters confounding behavioural experiments, which include novelty, fear and stress due to restrain, amongst others.</p> <p>Results</p> <p>We have developed an improved assay which overcomes these confounding factors and enables studying USVs in freely moving mice repetitively over several weeks. Using this improved assay, we report here that USVs increase significantly in mice with bone metastases-induced cancer pain or neuropathic pain for several weeks, in comparison to sham-treated mice. Importantly, analgesic drugs which are known to alleviate tumour pain or neuropathic pain in human patients significantly reduce USVs as well as mechanical allodynia in corresponding mouse models.</p> <p>Conclusions</p> <p>We show that studying USVs and mechanical allodynia in the same cohort of mice enables comparing the temporal progression of on-going pain (i.e. stimulus-independent pain) and stimulus-evoked pain in these clinically highly-relevant forms of chronic pain.</p

Biological aspects of the Indo-Pacific sergeant Abudefduf vaigiensis (Quoy and Gaimard, 1825) from Gulf of Mannar, Tamil Nadu, India

Food and feeding habits of the commercially important marine ornamental fish Abudefduf vaigiensis from the Gulf of Mannar were evaluated. Analysis of gut contents indicated that A. vaigiensis is an omnivorous fish, feeding on any available food item in its environment, such as seaweeds, cladocerans, copepods and insects. Most of the sampled fishes had either quarter-full or half-full or three-fourth full stomachs. The index of preponderance indicated seaweeds as the preferred food item among majority of length classes except for those falling within the 80-89 and 100-109 length classes, in which a preference towards copepods was observed. On a monthly basis, seaweed Spongomorpha sp. emerged as the predominant food item. Gastro-somatic index (GaSI) for males recorded the highest value in July (1.20) and lowest (0.36) in November, while that of females recorded the highest value in July (0.95) and lowest value (0.47) in January. Hepato-somatic index (HSI) of females recorded the highest in December (2.01) and lowest in July (0.83), while that of males recorded the highest value in January (1.25) and lowest in September (0.81). Gonadosomatic index (GSI) in females recorded maximum in February (4.23) and lowest in June (1.32) while that of males recorded the highest value in February (0.85) and lowest value in July (0.35). The results of the study indicate that adopting seasonal regulatory measures is essential for sustainable exploitation of the species, since their trade relies on wild collection. The study also revealed a negative correlation between the feeding patterns of these fish and their reproductive development

Neuropathic pain caused by miswiring and abnormal end organ targeting

Nerve injury leads to chronic pain and exaggerated sensitivity to gentle touch (allodynia) as well as a loss of sensation in the areas in which injured and non-injured nerves come together1-3. The mechanisms that disambiguate these mixed and paradoxical symptoms are unknown. Here we longitudinally and non-invasively imaged genetically labelled populations of fibres that sense noxious stimuli (nociceptors) and gentle touch (low-threshold afferents) peripherally in the skin for longer than 10 months after nerve injury, while simultaneously tracking pain-related behaviour in the same mice. Fully denervated areas of skin initially lost sensation, gradually recovered normal sensitivity and developed marked allodynia and aversion to gentle touch several months after injury. This reinnervation-induced neuropathic pain involved nociceptors that sprouted into denervated territories precisely reproducing the initial pattern of innervation, were guided by blood vessels and showed irregular terminal connectivity in the skin and lowered activation thresholds mimicking low-threshold afferents. By contrast, low-threshold afferents-which normally mediate touch sensation as well as allodynia in intact nerve territories after injury4-7-did not reinnervate, leading to an aberrant innervation of tactile end organs such as Meissner corpuscles with nociceptors alone. Genetic ablation of nociceptors fully abrogated reinnervation allodynia. Our results thus reveal the emergence of a form of chronic neuropathic pain that is driven by structural plasticity, abnormal terminal connectivity and malfunction of nociceptors during reinnervation, and provide a mechanistic framework for the paradoxical sensory manifestations that are observed clinically and can impose a heavy burden on patients.The research leading to these results has received funding from the following sources: an ERC Advanced Investigator grant to R.K. (Pain Plasticity 294293); grants from the Deutsche Forschungsgemeinschaft to R.K. (SFB1158, projects B01, B06), to T.K. (SFB1158, project B08), to S.G.L. (SFB1158, project A01) and to V.G. (SFB1158, project A03); a grant to B.O. (project number 371923335); and grant CIDEGENT/2020/052 from Generalitat Valenciana to F.J.T. R.K. is a member of the Molecular Medicine Partnership Unit of the European Molecular Biology Laboratory and Medical Faculty Heidelberg. V.G. and T.A.N. were partially supported by a post-doctoral fellowship and physician scientist fellowship, respectively, from the Medical Faculty Heidelberg. D.M. was partially supported by a post-doctoral fellowship from Excellence Cluster CellNetworks. We acknowledge support from the Interdisciplinary Neurobehavioral Core (INBC) for the behavioural experiments, the data storage service SDS@hd and bwMLS&WISO HPC supported by the state of Baden-Württemberg and the German Research Foundation (DFG) through grants INST 35/1314-1 FUGG and INST 35/1134-1 FUGG, respectively.Peer reviewe

A Review on Prevalence of Inflammatory Bowel Disease in India

Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD) was believed to be a Western disease, but are now increasingly being reported from India and other Asian countries where IBD was almost unheard of 30 years ago. Now India is projected to have one of the highest IBD burden across the world. There is rising incidence and prevalence of IBD in India topping the Southeast Asian countries. The clinical presentation of IBD in India is similar to other South East Asian countries. IBD is considered as a result of the complex interaction between the environment, diet, certain medications, genetic variables and a severe autoimmune response against normal bacteria in the gut. However exact cause is still unknown. Also there exists a gender distribution in IBD. In India IBD is more prevalent in males compared to females. This review summarizes the prevalence of IBD in India and some possible risk factors contributing to it. Keywords: Inflammatory bowel disease, prevalence, Indi