bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistence of pain in humans and other mammals
Authors: Williams Amanda C. de C. 
Published: September 2019

Evolutionary models of chronic pain are relatively undeveloped, but mainly concern dysregulation of an efficient acute defence, or false alarm. Here, a third possibility, mismatch with the modern environment, is examined. In ancestral human and free-living animal environments, survival needs urge a return to activity during recovery, despite pain, but modern environments allow humans and domesticated animals prolonged inactivity after injury. This review uses the research literature to compare humans and other mammals, who share pain neurophysiology, on risk factors for pain persistence, behaviours associated with pain, and responses of conspecifics to behaviours. The mammal populations studied are mainly laboratory rodents in pain research, and farm and companion animals in veterinary research, with observations of captive and free-living primates. Beyond farm animals and rodent models, there is virtually no evidence of chronic pain in other mammals. Since evidence is sparse, it is hard to conclude that it does not occur, but its apparent absence is compatible with the mismatch hypothesis.
This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Listening to your gut: immune challenge to the gut sensitizes body wall nociception in the caterpillarManduca sexta
Authors: Adamo Shelley A. , McMillan Laura E. 
Published: September 2019

Immune–nociceptor connections are found in animals across phyla. Local inflammation and/or damage results in increased nociceptive sensitivity of the affected area. However, in mammals, immune responses far from peripheral nociceptors, such as immune responses in the gut, produce a general increase in peripheral nociceptive sensitivity. This phenomenon has not, to our knowledge, been found in other animal groups. We found that consuming heat-killed pathogens reduced the tactile force needed to induce a defensive strike in the caterpillarManduca sexta. This increase in the nociceptive sensitivity of the body wall is probably part of the reconfiguration of behaviour and physiology that occurs during an immune response (e.g. sickness behaviour). This increase may help enhance anti-predator behaviour as molecular resources are shifted towards the immune system.This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Early-life injury produces lifelong neural hyperexcitability, cognitive deficit and altered defensive behaviour in the squidEuprymna scolopes
Authors: Howard Ryan B. , Lopes Lauren N. , Lardie Christina R. , Perez Paul P. , Crook Robyn J. 
Published: September 2019

Injury occurring in the neonatal period in mammals is known to induce plasticity in pain pathways that may lead to pain dysfunction in later life. Whether these effects are unique to the mammalian nervous system is not well understood. Here, we investigate whether similar effects of early-life injury are found in a large-brained comparative model, the cephalopodEuprymna scolopes. We show that the peripheral nervous system ofE. scolopesundergoes profound and permanent plasticity after injury of peripheral tissue in the early post-hatching period, but not after the same injury given in the later juvenile period. Additionally, both innate defensive behaviour and learning are impaired by injury in early life. We suggest that these similar patterns of nervous system and behavioural remodelling that occur in squid and in mammals indicate an adaptive value for long-lasting plasticity arising from early-life injury, and suggest that injuries inflicted in very early life may signal to the nervous system that the environment is highly dangerous. Thus, neonatal pain plasticity may be a conserved pattern whose purpose is to set the developing nervous system's baseline responsiveness to threat.This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
The facial expression of pain in humans considered from a social perspective
Authors: Kappesser Judith 
Published: September 2019

The social modulation of pain in humans has been neglected so far with respect to verbal as well as non-verbal communication of pain. The facial pain expression is a powerful way to communicate pain, and there are some theoretical accounts available on how social modulation may affect the encoding of the facial expression of pain. Some accounts, particularly in the pain field, are proximate explanations on the mechanisms involved, whereas an evolutionary psychology account takes a more comprehensive approach. A review of nine experimental studies revealed that in the majority of studies (6/9), social context had an effect on the facial pain expression, but results were inconsistent. Several conceptual and methodological issues are discussed which may explain these inconsistencies and could help in design of future experimental studies.
This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
The translatability of pain across species
Authors: Mogil Jeffrey S. 
Published: September 2019

The poor translational record of pain research has suggested to some observers that species differences in pain biology might be to blame. In this review, I consider the evidence for species similarity and differences in the pain research literature. Impressive feats of translation have been demonstrated in relation to certain genetic effects, social modulation of pain and pain memory. The degree to which pain biology in rodents predicts pain biology in humans has important implications both for evolutionary accounts of pain, but also the success of analgesic drug development going forward.
This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Peripheralstraightjacket(α2δ Ca2+channel subunit) expression is required for neuropathic sensitization inDrosophila
Authors: Khuong Thang M. , Hamoudi Zina , Manion John , Loo Lipin , Muralidharan Arjun , Neely G. Gregory 
Published: September 2019

Nerve injury leads to devastating and often untreatable neuropathic pain. While acute noxious sensation (nociception) is a crucial survival mechanism and is conserved across phyla, chronic neuropathic pain is considered a maladaptive response owing to its devastating impact on a patient's quality of life. We have recently shown that a neuropathic pain-like response occurs in adultDrosophila. However, the mechanisms underlying this phenomenon are largely unknown. Previous studies have shown that the α2δ peripheral calcium channel subunitstraightjacket(stj) is a conserved factor required for thermal pain perception. We demonstrate here thatstjis required in peripheralppk+sensory neurons for acute thermal responses and that it mediates nociceptive hypersensitivity in an adultDrosophilamodel of neuropathic pain-like disease. Given that calcium channels are the main targets of gabapentinoids (pregabalin and gabapentin), we assessed if these drugs can alleviate nociceptive hypersensitivity. Our findings suggest that gabapentinoids may prevent nociceptive hypersensitivity by preserving central inhibition after nerve injury. Together, our data further highlight the similarity of some mechanisms for pain-like conditions acrossphylaand validates the scientific use ofDrosophilaneuropathic sensitization models for analgesic drug discovery.This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Evolution of nociception and pain: evidence from fish models
Authors: Sneddon Lynne U. 
Published: September 2019

In order to survive, animals must avoid injury and be able to detect potentially damaging stimuli via nociceptive mechanisms. If the injury is accompanied by a negative affective component, future behaviour should be altered and one can conclude the animal experienced the discomfort associated with pain. Fishes are the most successful vertebrate group when considering the number of species that have filled a variety of aquatic niches. The empirical evidence for nociception in fishes from the underlying molecular biology, neurobiology and anatomy of nociceptors through to whole animal behavioural responses is reviewed to demonstrate the evolutionary conservation of nociception and pain from invertebrates to vertebrates. Studies in fish have shown that the biology of the nociceptive system is strikingly similar to that found in mammals. Further, potentially painful events result in behavioural and physiological changes such as reduced activity, guarding behaviour, suspension of normal behaviour, increased ventilation rate and abnormal behaviours which are all prevented by the use of pain-relieving drugs. Fish also perform competing tasks less well when treated with a putative painful stimulus. Therefore, there is ample evidence to demonstrate that it is highly likely that fish experience pain and that pain-related behavioural changes are conserved across vertebrates.
This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Evolution of acid nociception: ion channels and receptors for detecting acid
Authors: Pattison Luke A. , Callejo Gerard , St John Smith Ewan 
Published: September 2019

Nociceptors, i.e. sensory neurons tuned to detect noxious stimuli, are found in numerous phyla of the Animalia kingdom and are often polymodal, responding to a variety of stimuli, e.g. heat, cold, pressure and chemicals, such as acid. Owing to the ability of protons to have a profound effect on ionic homeostasis and damage macromolecular structures, it is no wonder that the ability to detect acid is conserved across many species. To detect changes in pH, nociceptors are equipped with an assortment of different acid sensors, some of which can detect mild changes in pH, such as the acid-sensing ion channels, proton-sensing G protein-coupled receptors and several two-pore potassium channels, whereas others, such as the transient receptor potential vanilloid 1 ion channel, require larger shifts in pH. This review will discuss the evolution of acid sensation and the different mechanisms by which nociceptors can detect acid.This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Discrimination between nociceptive reflexes and more complex responses consistent with pain in crustaceans
Authors: Elwood Robert W. 
Published: September 2019

Animals have quick-acting nociceptive reflexes that protect them from tissue damage. Some taxa have also evolved the capacity for pain. Pain appears to be linked to long-term changes in motivation brought about by the aversive nature of the experience. Pain presumably enhances long-term protection through behaviour modification based, in part, on memory. However, crustaceans have long been viewed as responding purely by reflex and thus not experiencing pain. This paper considers behavioural and physiological criteria that distinguish nociception from potential pain in this taxon. These include trade-offs with other motivational systems and prolonged motivational change. Complex, prolonged grooming or rubbing demonstrate the perception of the specific site of stimulus application. Recent evidence of fitness-enhancing, anxiety-like states is also consistent with the idea of pain. Physiological changes in response to noxious stimuli mediate some of the behavioural change. Rapid avoidance learning and prolonged memory indicate central processing rather than mere reflexes. Thus, available data go beyond the idea of just nociception. However, the impossibility of total proof of pain described in ways appropriate for our own species means that pain in crustaceans is still disputed. Pain in animals should be defined in ways that do not depend on human pain experience.This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.
Self-reported Morisky 8 item medication adherence scale to statins concords with pill count method and correlates with serum lipid profile parameters and Serum HMGCoA Reductase levels
Authors: Grover Abhinav , Oberoi Mansi , Rehan Harmeet , Gupta Lalit , Yadav Madhur 
Published: September 2019

ABSTRACTBackgroundIt is imperative that non-compliance to statins be identified and addressed to optimize the clinical benefit of statins. Patient self-reporting methods are convenient to apply in clinical practice but need to be validated.ObjectiveWe studied the concordance of a patient self-report method, MMAS (Morisky eight item medication adherence scale) with pill count method in measuring adherence to statins and their correlation with extended lipid profile parameters and serum HMGCoA-R (hydroxymethylglutaryl coenzyme A reductase) enzyme levels.MethodsMMAS and pill count method were used to measure the adherence to statins in patients on statins for any duration. Patients were subjected to estimation of extended lipid profile and serum HMGCoA-R levels at the end of 3 months follow-up.ResultsOut of a total of 200 patients included in the study, 117 patients had low adherence (score less than 6 on MMAS) whereas 65 and 18 patients had medium (score 6 to less than 8) and high adherence (score of 8) respectively. Majority of patients who had low adherence to statins by MMAS were nonadherent by pill count method yielding concordance of 96.5%. Medium or high adherence to statins by MMAS method had concordance of 89.1% with pill count method. The levels of total cholesterol, low density lipoprotein-cholesterol, apolipoprotein B and HMGCoA-R were significantly negatively correlated with compliance measured by pill count and MMAS with similar correlation coefficients. HMGCoA-R levels demonstrated a plateau phenomenon with levels being 9-10 ng/ml when compliance to statin therapy was greater than 60% by pill count and greater than 6 on Morisky scale.ConclusionIn conclusion, MMAS and pill count methods showed concordance in measuring adherence to statins. These methods need to be explored further for their interchangeability as surrogates for biomarker levels.
A mosquito survey along a transect of urbanization in Dschang, West Region of Cameroon, reveals potential risk of arbovirus spillovers
Authors: Audrey Mayi Marie Paul , Roland Bamou , Borel Djiappi-Tchamen , Carelle Djojo-Tachegoum , Albin Fontaine , Christophe Antonio-Nkondjio , Timoleon Tchuinkam 
Published: September 2019

AbstractBackgroundWith the advance of globalization and the decline of wild habitats, mosquito-borne viruses are no longer confined to their original sylvatic environments and are emerging or remerging worldwide. However, little is known about the mosquito species implicated in the spillovers of these viruses from their enzootic cycles.MethodWe conducted an entomological field survey to catalogue the relative abundance of the Culicidae fauna in rural, peri-urban and urban areas in the Dschang locality in West Cameroon. Mosquitoes were collected from March-April and July-August 2019 at both aquatic and adult stages, and identified using stereomicroscopes and morphological identification keys.ResultsA total of 1,401 mosquitoes belonging to 4 genera and 26 species were collected (n=427, 470 and 504 in rural, peri-urban and urban areas respectively). The most abundant species Aedes africanus (45.47%) as well as Culex moucheti (8.92 %) were encountered in peri-urban and rural environments. Species like Culex duttoni (14.49%), Culex quinquefasciatus (2.35%) and Aedes aegypti (1.36%) were solely found in urban area. Aedes albopictus (14.42%), Culex (Culiciomyia) (6.57%), Culex tigripes (1.43%) and Eretmapodites chrysogaster (0.64%) on the other hand were collected in the three study sites. Importantly, all these species have been suspected or incriminated as vectors of many arboviruses.ConclusionThis study identified potential sylvatic, urban and bridge-vectors that can play a role in current or future virus emergence in Cameroon. Further investigations are needed to assess if arboviruses are circulating in these areas and to study the vector role of each mosquito species in arbovirus transmission.
Differential Nr4a1 and Nr4a3 expression discriminates tonic from activated TCR signalling events in vivo
Authors: Jennings Emma , Elliot Thomas A.E. , Thawait Natasha , Kanabar Shivani , Yam-Puc Juan Carlos , Ono Masahiro , Toellner Kai-Michael , Wraith David C. , Anderson Graham , Bending David 
Published: September 2019

SummaryNr4areceptors are activated by T cell receptor (TCR) and B cell receptor (BCR) signalling and play key roles in T cell differentiation and promoting T cell exhaustion. How TCR signalling pathways regulate Nr4a receptors and their sensitivities to different physiological types of TCR signalling (e.g. tonic versus activating) remains unknown. Here we utilise Nr4a1/Nur77-GFP andNr4a3-Tocky mice to elucidate the signalling pathways that govern Nr4a receptor expression in CD4+and CD8+T cells. Our findings reveal thatNr4a1-3are Src family kinase-dependent. Moreover,Nr4a2andNr4a3are abolished by calcineurin inhibitors and bind NFAT1, highlighting a necessary and sufficient role for NFAT in the control ofNr4a2andNr4a3, but redundancy for NFAT forNr4a1. During T cell development, Nr4a1 is activated by tonic signalling during TCR-beta selection in the thymus, whilst Nr4a3 requires cognate peptide:MHC interactions for expression. Thus, due to differential sensitivity of Nr4a1 and Nr4a3 to TCR signalling pathways, T cells undergoing tonic versus activating TCR signalling events can be distinguished in vivo.
Inertial sensor-based centripetal acceleration as a correlate for lateral margin of stability during walking and turning
Authors: Fino Peter C. , Horak Fay B. , Curtze Carolin 
Published: September 2019

AbstractThere is growing interest in using inertial sensors to continuously monitor gait during free-living mobility. Inertial sensors can provide many gait measures, but they struggle to capture the spatial stability of the center-of-mass due to limitations estimating sensor-to-sensor distance. While the margin of stability (MoS) is an established outcome describing the instantaneous mechanical stability of gait relating to fall-risk, methods to estimate the MoS from inertial sensors have been lacking. Here, we developed and tested a framework, based on centripetal acceleration, to determine a correlate for the lateral MoS using inertial sensors during walking with or without turning. Using three synchronized sensors located bilaterally on the feet and lumbar spine, the average centripetal acceleration over the subsequent step can be used as a correlate for lateral MoS. Relying only on a single sensor on the lumbar spine yielded similar results if the stance foot can be determined from other means. Additionally, the centripetal acceleration correlate of lateral MoS demonstrates clear differences between walking and turning, inside and outside turning limbs, and speed. While limitations and assumptions need to be considered when implemented in practice, this method presents a novel correlate for the lateral MoS during walking and turning using inertial sensors, although further validation is required for other activities and populations.
Cortical auditory distance representation based on direct-to-reverberant energy ratio
Authors: Kopco Norbert , Doreswamy Keerthi Kumar , Huang Samantha , Rossi Stephanie , Ahveninen Jyrki 
Published: September 2019

AbstractAuditory distance perception and its neuronal mechanisms are poorly understood, mainly because 1) it is difficult to separate distance processing from intensity processing, 2) multiple intensity-independent distance cues are often available, and 3) the cues are combined in a context-dependent way. A recent fMRI study identified human auditory cortical area representing intensity-independent distance for sources presented along the interaural axis (Kopco et al., PNAS, 109, 11019-11024). For these sources, two intensity-independent cues are available, interaural level difference (ILD) and direct-to-reverberant energy ratio (DRR). Thus, the observed activations may have been contributed by not only distance-related, but also direction-encoding neuron populations sensitive to ILD. Here, the paradigm from the previous study was used to examine DRR-based distance representation for sounds originating in front of the listener, where ILD is not available. In a virtual environment, we performed behavioral and fMRI experiments, combined with computational analyses to identify the neural representation of distance based on DRR. The stimuli varied in distance (15-100 cm) while their received intensity was varied randomly and independently of distance. Behavioral performance showed that intensity-independent distance discrimination is accurate for frontal stimuli, even though it is worse than for lateral stimuli. fMRI activations for sounds varying in frontal distance, as compared to varying only in intensity, increased bilaterally in the posterior banks of Heschl's gyri, the planum temporale, and posterior superior temporal gyrus regions. Taken together, these results suggest that posterior human auditory cortex areas contain neuron populations that are sensitive to distance independent of intensity and of binaural cues relevant for directional hearing.HighlightsPosterior auditory cortices (AC) are sensitive to frontally presented distance cuesThese effects are independent of intensity- and direction-related binaural cuesfMRI activations to frontal distance cues are found in the right and left ACThe frontal reverberation-related auditory distance cues are behaviorally relevant