scholarly journals An evolutionary medicine perspective on pain and its disorders

2019 ◽  
Vol 374 (1785) ◽  
pp. 20190288 ◽  
Author(s):  
Randolph M. Nesse ◽  
Jay Schulkin
Keyword(s):  
Chronic Pain ◽  
Tissue Damage ◽  
Mental States ◽  
Preliminary Evidence ◽  
Evolutionary Medicine ◽  
Smoke Detector ◽  
Pain Mechanisms ◽  
Trade Offs ◽  
Pathological Pain ◽  
The Cost

Enormous progress in understanding the mechanisms that mediate pain can be augmented by an evolutionary medicine perspective on how the capacity for pain gives selective advantages, the trade-offs that shaped the mechanisms, and evolutionary explanations for the system's vulnerability to excessive and chronic pain. Syndromes of deficient pain document tragically the utility of pain to motivate escape from and avoidance of situations causing tissue damage. Much apparently excessive pain is actually normal because the cost of more pain is often vastly less than the cost of too little pain (the smoke detector principle). Vulnerability to pathological pain may be explained in part because natural selection has shaped mechanisms that respond adaptively to repeated tissue damage by decreasing the pain threshold and increasing pain salience. The other half of an evolutionary approach describes the phylogeny of pain mechanisms; the apparent independence of different kinds of pain is of special interest. Painful mental states such as anxiety, guilt and low mood may have evolved from physical pain precursors. Preliminary evidence for this is found in anatomic and genetic data. Such insights from evolutionary medicine may help in understanding vulnerability to chronic pain. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.

scholarly journals Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain

2021 ◽  
Author(s):  
Annemarie Dedek ◽  
Jian Xu ◽  
Louis-Étienne Lorenzo ◽  
Antoine G. Godin ◽  
Chaya M. Kandegedara ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sexual Dimorphism ◽  
Nmda Receptor ◽  
Ex Vivo ◽  
Female Rats ◽  
Pain Mechanisms ◽  
Human Organ ◽  
Neuronal Mechanism ◽  
Lamina I ◽  
Pathological Pain

The prevalence and severity of many chronic pain syndromes differ across sex, and recent studies have identified differences in immune signalling within spinal nociceptive circuits as a potential mediator. Although it has been proposed that sex-specific pain mechanisms converge once they reach neurons within the superficial dorsal horn (SDH), direct investigations using rodent and human preclinical pain models have been lacking. Here, we discovered that in the Freund′s Adjuvant in vivo model of inflammatory pain, where both male and female rats display tactile allodynia, a pathological coupling between KCC2-dependent disinhibition and NMDA receptor potentiation within SDH neurons was observed in male but not female rats. Unlike males, the neuroimmune mediator, BDNF, failed to downregulate inhibitory signalling elements (KCC2 and STEP61) and upregulate excitatory elements (pFyn, GluN2B, and pGluN2B) in female rats, resulting in no effect of ex vivo BDNF on synaptic NMDA receptor responses in female lamina I neurons. Importantly, this sex difference in spinal pain processing was conserved from rodents to humans. As in rodents, ex vivo spinal treatment with BDNF downregulated markers of disinhibition and upregulated markers of facilitated excitation in SDH neurons from male but not female human organ donors. Ovariectomy in female rats recapitulated the male pathological pain neuronal phenotype, with BDNF driving a coupling between disinhibition and NMDA receptor potentiation in adult lamina I neurons following the prepubescent elimination of sex hormones in females. This discovery of sexual dimorphism in a central neuronal mechanism of chronic pain across species provides a foundational step towards a better understanding and treatment for pain in both sexes.

scholarly journals MODERN VIEW OF DIAGNOSIS AND APPROACHES TO THE TREATMENT OF CHRONIC PAIN IN CHILDREN WITH PARALYTIC SYNDROMES (LITERATURE REVIEW)

2021 ◽  
Vol 11 (4(42)) ◽  
pp. 60-67
Author(s):  
N. Orlova ◽  
O. Riga
Keyword(s):  
Chronic Pain ◽  
Tissue Damage ◽  
Cultural Context ◽  
Medical Condition ◽  
International Association ◽  
Emotional Experience ◽  
Recovery Period ◽  
Medical Science ◽  
The Body ◽  
Pain Mechanisms

Over the past decades, more and more attention in medical science has been paid to the diagnosis and study of pain mechanisms in the pediatric population. According to experts in the field of chronic pain in children, it occurs in 12% of all pediatric patients, which negatively affects the quality of children’s life and life of their families. Today, a particularly important problem in most countries of the world is pain in children with paralytic syndromes of III - V level according to GMFCS. About 20-35% of children with paralytic syndromes suffer from chronic pain. Although there are means and knowledge on how to treat pain, children's pain is often not recognized, ignored, or even denied. More than 50% of children with paralytic syndromes suffer from moderate to severe pain daily and in several parts of the body. The International Association for the Study of Pain (IASP) defines pain as “an unpleasant, sensual, and emotional experience associated with actual or potential tissue damage or perceived tissue damage. The inability to communicate verbally does not negate the possibility that the individual is in pain and needs appropriate analgesic treatment. Pain is always subjective ... ". Determining the type of pain helps to identify its cause, which can guide the choice of treatment. The main cause of pain in children includes acute nociceptive pain (ie pain caused by activation of peripheral nerve endings, including somatic and visceral pain), neuropathic pain (ie due to damage or dysfunction of the somatosensory system), psychosocial - spiritual - emotional pain. Chronic pain is a continuous or intermittent pain that lasts longer than the expected normal recovery period. Chronic pain can also occur and persist in the absence of a specific pathophysiology or medical condition. The expression of pain depends on a child's age, cognitive development and socio-cultural context.

Dorsal Horn Pain Mechanisms

2019 ◽  
pp. 444-469 ◽  
Author(s):  
Hanns Ulrich Zeilhofer ◽  
Robert Ganley
Keyword(s):  
Dorsal Horn ◽  
Neuronal Excitability ◽  
Functional Organization ◽  
Synaptic Integration ◽  
Synaptic Efficacy ◽  
Pain Mechanisms ◽  
Pain Pathway ◽  
Pathological Pain ◽  
The Subject ◽  
Equivalent Structure

The spinal dorsal horn and its equivalent structure in the brainstem constitute the first sites of synaptic integration in the pain pathway. A huge body of literature exists on alterations in spinal nociceptive signal processing that contribute to the generation of exaggerated pain states and hence to what is generally known as “central sensitization.” Such mechanisms include changes in synaptic efficacy or neuronal excitability, which can be evoked by intense nociceptive stimulation or by inflammatory or neuropathic insults. Some of these changes cause alterations in the functional organization of dorsal horn sensory circuits, leading to abnormal pathological pain sensations. This article reviews the present state of this knowledge. It does not cover the contributions of astrocytes and microglia in detail as their functions are the subject of a separate chapter.

scholarly journals Adaptive mechanisms driving maladaptive pain: how chronic ongoing activity in primary nociceptors can enhance evolutionary fitness after severe injury

2019 ◽  
Vol 374 (1785) ◽  
pp. 20190277 ◽  
Author(s):  
Edgar T. Walters
Keyword(s):  
Chronic Pain ◽  
Motor Impairment ◽  
Low Frequency ◽  
Severe Injury ◽  
Ongoing Activity ◽  
Pain Mechanisms ◽  
Bodily Injury ◽  
Adaptive Mechanisms ◽  
Survival And Reproduction ◽  
Ongoing Pain

Chronic pain is considered maladaptive by clinicians because it provides no apparent protective or recuperative benefits. Similarly, evolutionary speculations have assumed that chronic pain represents maladaptive or evolutionarily neutral dysregulation of acute pain mechanisms. By contrast, the present hypothesis proposes that chronic pain can be driven by mechanisms that evolved to reduce increased vulnerability to attack from predators and aggressive conspecifics, which often target prey showing physical impairment after severe injury. Ongoing pain and anxiety persisting long after severe injury continue to enhance vigilance and behavioural caution, decreasing the heightened vulnerability to attack that results from motor impairment and disfigurement, thereby increasing survival and reproduction (fitness). This hypothesis is supported by evidence of animals surviving and reproducing after traumatic amputations, and by complex specializations that enable primary nociceptors to detect local and systemic signs of injury and inflammation, and to maintain low-frequency discharge that can promote ongoing pain indefinitely. Ongoing activity in nociceptors involves intricate electrophysiological and anatomical specializations, including inducible alterations in the expression of ion channels and receptors that produce persistent hyperexcitability and hypersensitivity to chemical signals of injury. Clinically maladaptive chronic pain may sometimes result from the recruitment of this powerful evolutionary adaptation to severe bodily injury. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.

scholarly journals A framework for reducing the overhead of the quantum oracle for use with Grover’s algorithm with applications to cryptanalysis of SIKE

2020 ◽  
Vol 15 (1) ◽  
pp. 143-156
Author(s):  
Jean-François Biasse ◽  
Benjamin Pring
Keyword(s):  
Search Algorithm ◽  
Circuit Complexity ◽  
Quantum Circuit ◽  
Grover’S Algorithm ◽  
Search Problems ◽  
Trade Offs ◽  
Single Target ◽  
Grover's Algorithm ◽  
Quantum Oracle ◽  
The Cost

AbstractIn this paper we provide a framework for applying classical search and preprocessing to quantum oracles for use with Grover’s quantum search algorithm in order to lower the quantum circuit-complexity of Grover’s algorithm for single-target search problems. This has the effect (for certain problems) of reducing a portion of the polynomial overhead contributed by the implementation cost of quantum oracles and can be used to provide either strict improvements or advantageous trade-offs in circuit-complexity. Our results indicate that it is possible for quantum oracles for certain single-target preimage search problems to reduce the quantum circuit-size from $O\left(2^{n/2}\cdot mC\right)$ (where C originates from the cost of implementing the quantum oracle) to $O(2^{n/2} \cdot m\sqrt{C})$ without the use of quantum ram, whilst also slightly reducing the number of required qubits.This framework captures a previous optimisation of Grover’s algorithm using preprocessing [21] applied to cryptanalysis, providing new asymptotic analysis. We additionally provide insights and asymptotic improvements on recent cryptanalysis [16] of SIKE [14] via Grover’s algorithm, demonstrating that the speedup applies to this attack and impacting upon quantum security estimates [16] incorporated into the SIKE specification [14].

scholarly journals Wideband Rectangular Foldable and Non-foldable Antenna for Internet of Things Applications

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Steve W. Y. Mung ◽  
Cheuk Yin Cheung ◽  
Ka Ming Wu ◽  
Joseph S. M. Yuen
Keyword(s):  
Internet Of Things ◽  
Printed Circuit Board ◽  
Circuit Board ◽  
Design Parameters ◽  
Multiple Frequency ◽  
Wireless Applications ◽  
Printed Circuit ◽  
Iot Applications ◽  
Trade Offs ◽  
The Cost

This article presents a simple wideband rectangular antenna in foldable and non-foldable (printed circuit board (PCB)) structures for Internet of Things (IoT) applications. Both are simple structures with two similar rectangular metal planes which cover multiple frequency bands such as GPS, WCDMA/LTE, and 2.4 GHz industrial, scientific, and medical (ISM) bands. This wideband antenna is suitable to integrate into the short- and long-range wireless applications such as the short-range 2.4 GHz ISM band and standard cellular bands. This lowers the overall size of the product as well as the cost in the applications. In this article, the configuration and operation principle are presented as well as its trade-offs on the design parameters. Simulated and experimental results of foldable and non-foldable (PCB) structures show that the antenna is suited for IoT applications.

Demographic life history traits of reproductive natterjack toads (Bufo calamita) vary between northern and southern latitudes

2006 ◽  
Vol 27 (3) ◽  
pp. 365-375 ◽  
Author(s):  
Delfi Sanuy ◽  
Christoph Leskovar ◽  
Neus Oromi ◽  
Ulrich Sinsch
Keyword(s):  
Life History ◽  
Life History Traits ◽  
Large Female ◽  
Breeding Period ◽  
Female Size ◽  
Data Set ◽  
Bufo Calamita ◽  
Trade Offs ◽  
Age Variation ◽  
The Cost

AbstractDemographic life history traits were investigated in three Bufo calamita populations in Germany (Rhineland-Palatinate: Urmitz, 50°N; 1998-2000) and Spain (Catalonia: Balaguer, Mas de Melons, 41°N; 2004). We used skeletochronology to estimate the age as number of lines of arrested growth in breeding adults collected during the spring breeding period (all localities) and during the summer breeding period (only Urmitz). A data set including the variables sex, age and size of 185 males and of 87 females was analyzed with respect to seven life history traits (age and size at maturity of the youngest first breeders, age variation in first breeders, longevity, potential reproductive lifespan, median lifespan, age-size relationship). Spring and summer cohorts at the German locality differed with respect to longevity and potential reproductive lifespan by one year in favour of the early breeders. The potential consequences on fitness and stability of cohorts are discussed. Latitudinal variation of life history traits was mainly limited to female natterjacks in which along a south-north gradient longevity and potential reproductive lifespan increased while size decreased. These results and a review of published information on natterjack demography suggest that lifetime number of offspring seem to be optimized by locally different trade-offs: large female size at the cost of longevity in southern populations and increased longevity at the cost of size in northern ones.

HCN2 ion channels: basic science opens up possibilities for therapeutic intervention in neuropathic pain

2016 ◽  
Vol 473 (18) ◽  
pp. 2717-2736 ◽  
Author(s):  
Christoforos Tsantoulas ◽  
Elizabeth R. Mooney ◽  
Peter A. McNaughton
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Ion Channels ◽  
Warning Signal ◽  
Sensory Nerves ◽  
Nociceptive Neurons ◽  
Pain Syndromes ◽  
Medical Need ◽  
Pathological Pain ◽  
Genetic Deletion

Nociception — the ability to detect painful stimuli — is an invaluable sense that warns against present or imminent damage. In patients with chronic pain, however, this warning signal persists in the absence of any genuine threat and affects all aspects of everyday life. Neuropathic pain, a form of chronic pain caused by damage to sensory nerves themselves, is dishearteningly refractory to drugs that may work in other types of pain and is a major unmet medical need begging for novel analgesics. Hyperpolarisation-activated cyclic nucleotide (HCN)-modulated ion channels are best known for their fundamental pacemaker role in the heart; here, we review data demonstrating that the HCN2 isoform acts in an analogous way as a ‘pacemaker for pain’, in that its activity in nociceptive neurons is critical for the maintenance of electrical activity and for the sensation of chronic pain in pathological pain states. Pharmacological block or genetic deletion of HCN2 in sensory neurons provides robust pain relief in a variety of animal models of inflammatory and neuropathic pain, without any effect on normal sensation of acute pain. We discuss the implications of these findings for our understanding of neuropathic pain pathogenesis, and we outline possible future opportunities for the development of efficacious and safe pharmacotherapies in a range of chronic pain syndromes.

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