Current issues in fish welfare

Human beings may affect the welfare of fish through fisheries, aquaculture and a number of other activities. There is no agreement on just how to weigh the concern for welfare of fish against the human interests involved, but ethical frameworks exist that suggest how this might be approached. Different definitions of animal welfare focus on an animal's condition, on its subjective experience of that condition and/or on whether it can lead a natural life. These provide different, legitimate, perspectives, but the approach taken in this paper is to focus on welfare as the absence of suffering. An unresolved and controversial issue in discussions about animal welfare is whether non‐human animals exposed to adverse experiences such as physical injury or confinement experience what humans would call suffering. The neocortex, which in humans is an important part of the neural mechanism that generates the subjective experience of suffering, is lacking in fish and non‐mammalian animals, and it has been argued that its absence in fish indicates that fish cannot suffer. A strong alternative view, however, is that complex animals with sophisticated behaviour, such as fish, probably have the capacity for suffering, though this may be different in degree and kind from the human experience of this state. Recent empirical studies support this view and show that painful stimuli are, at least, strongly aversive to fish. Consequently, injury or experience of other harmful conditions is a cause for concern in terms of welfare of individual fish. There is also growing evidence that fish can experience fear‐like states and that they avoid situations in which they have experienced adverse conditions. Human activities that potentially compromise fish welfare include anthropogenic changes to the environment, commercial fisheries, recreational angling, aquaculture, ornamental fish keeping and scientific research. The resulting harm to fish welfare is a cost that must be minimized and weighed against the benefits of the activity concerned. Wild fish naturally experience a variety of adverse conditions, from attack by predators or conspecifics to starvation or exposure to poor environmental conditions. This does not make it acceptable for humans to impose such conditions on fish, but it does suggest that fish will have mechanisms to cope with these conditions and reminds us that pain responses are in some cases adaptive (for example, suppressing feeding when injured). In common with all vertebrates, fish respond to environmental challenges with a series of adaptive neuro‐endocrine adjustments that are collectively termed the stress response. These in turn induce reversible metabolic and behavioural changes that make the fish better able to overcome or avoid the challenge and are undoubtedly beneficial, in the short‐term at least. In contrast, prolonged activation of the stress response is damaging and leads to immuno‐suppression, reduced growth and reproductive dysfunction. Indicators associated with the response to chronic stress (physiological endpoints, disease status and behaviour) provide a potential source of information on the welfare status of a fish. The most reliable assessment of well‐being will be obtained by examining a range of informative measures and statistical techniques are available that enable several such measures to be combined objectively. A growing body of evidence tells us that many human activities can harm fish welfare, but that the effects depend on the species and life‐history stage concerned and are also context‐dependent. For example, in aquaculture, adverse effects related to stocking density may be eliminated if good water quality is maintained. At low densities, bad water quality may be less likely to arise whereas social interactions may cause greater welfare problems. A number of key differences between fish and birds and mammals have important implications for their welfare. Fish do not need to fuel a high body temperature, so the effects of food deprivation on welfare are not so marked. For species that live naturally in large shoals, low rather than high densities may be harmful. On the other hand, fish are in intimate contact with their environment through the huge surface area of their gills, so they are vulnerable to poor water quality and water borne pollutants. Extrapolation between taxa is dangerous and general frameworks for ensuring welfare in other vertebrate animals need to be modified before they can be usefully applied to fish. The scientific study of fish welfare is at an early stage compared with work on other vertebrates and a great deal of what we need to know is yet to be discovered. It is clearly the case that fish, though different from birds and mammals, however, are sophisticated animals, far removed from unfeeling creatures with a 15 s memory of popular misconception. A heightened appreciation of these points in those who exploit fish and in those who seek to protect them would go a long way towards improving fish welfare.     

4-(3-Alkyl/benzyl-guanidino)benzenesulfonamides as selective carbonic anhydrase VII inhibitors

The treatment of chronic neuropathic pain remains one of the most challenging of all neurological diseases and very much an art. There exists no consensus for the optimal management of this condition at the moment. Gaining inspiration from recent studies which pointed out the involvement of brain-associated carbonic anhydrase (CA, EC 4.2.1.1) isoform VII in the pathology of various neurodegenerative diseases, which highlighted the relationship between selective inhibition of this isozyme and relieve of neuropathic pain, herein we report the synthesis and CA VII inhibitory activity of novel 4-(3-alkyl/benzyl-guanidino)benzenesulfonamides. Ten benzyl-substituted and five alkyl-substituted 4-guanidinobenzenesulfonamide derivatives were obtained, some of which (7c, 7h, 7m and 7o) exhibited satisfactory selectivity towards CA VII over CA I and II, with K_I-s in the subnanomolar range and good selectivity indexes for inhibiting the target versus the off-target isoforms.     

Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats

The endocannabinoid system (ECS) plays an important role in pain processing and modulation. Since the specific effects of endocannabinoids within the orofacial area are largely unknown, we aimed to determine whether an increase in the endocannabinoid concentration in the cerebrospinal fluid (CSF) caused by the peripheral administration of the FAAH inhibitor URB597 and tooth pulp stimulation would affect the transmission of impulses between the sensory and motor centers localized in the vicinity of the third and fourth cerebral ventricles. The study objectives were evaluated on rats using a method that allowed the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation and URB597 treatment. The amplitude of ETJ was a measure of the effect of endocannabinoids on the neural structures. The concentrations of the endocannabinoids tested (AEA and 2-AG) were determined in the CSF, along with the expression of the cannabinoid receptors (CB1 and CB2) in the tissues of the mesencephalon, thalamus, and hypothalamus. We demonstrated that anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), was significantly increased in the CSF after treatment with a FAAH inhibitor, while tooth pulp stimulation had no effect on the AEA and 2-AG concentrations in the CSF. We also found positive correlations between the CSF AEA concentration and cannabinoid receptor type 1 (CB1R) expression in the brain, and between 2-AG and cannabinoid receptor type 2 (CB2R), and negative correlations between the CSF concentration of AEA and brain CB2R expression, and between 2-AG and CB1R. Our study shows that endogenous AEA, which diffuses through the cerebroventricular ependyma into CSF and exerts a modulatory effect mediated by CB1Rs, alters the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve. In addition, our findings may be consistent with the emerging concept that AEA and 2-AG have different regulatory mechanisms because they are involved differently in orofacial pain. We also suggest that FAAH inhibition may offer a therapeutic approach to the treatment of orofacial pain.     

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain

Pain is a multidimensional perception that includes unpleasant somatosensory and affective experiences; however, the underlying neural circuits that mediate different components of pain remain elusive. Although hyperactivity of basolateral amygdala glutamatergic (BLA^Glu) neurons is required for the somatosensory and emotional processing of pain, the precise excitatory inputs to BLA^Glu neurons and their roles in mediating different aspects of pain are unclear. Here, we identified two discrete glutamatergic neuronal circuits in male mice: a projection from the insular cortex glutamatergic (IC^Glu) to BLA^Glu neurons, which modulates both the somatosensory and affective components of pain, and a projection from the mediodorsal thalamic nucleus (MD^Glu) to BLA^Glu neurons, which modulates only the aversive-affective component of pain. Using whole-cell recording and fiber photometry, we found that neurons within the IC→BLA and MD→BLA pathways were activated in mice upon inflammatory pain induced by injection of complete Freund’s adjuvant (CFA) into their paws. Optical inhibition of the IC^Glu→BLA pathway increased the nociceptive threshold and induced behavioral place preference in CFA mice. In contrast, optical inhibition of the MD^Glu→BLA pathway did not affect the nociceptive threshold but still induced place preference in CFA mice. In normal mice, optical activation of the IC^Glu→BLA pathway decreased the nociceptive threshold and induced place aversion, while optical activation of the MD^Glu→BLA pathway only evoked aversion. Taken together, our results demonstrate that discrete IC^Glu→BLA and MD^Glu→BLA pathways are involved in modulating different components of pain, provide insights into its circuit basis, and better our understanding of pain perception.     

The modification of cortical reorganization and chronic pain by sensory feedback

Recent neuroscientific evidence has revealed that the adult brain is capable of substantial plastic change in areas such as the primary somatosensory cortex that were formerly thought to be modifiable only during early experience. We discuss research on phantom limb pain as well as chronic back pain that revealed functional reorganization in both the somatosensory and the motor system in these chronic pain states. In phantom limb pain patients, cortical reorganization is correlated with the amount of phantom limb pain; in low back pain patients the amount of reorganizational change increases with chronicity. We present a model of the development of chronic pain that assumes an important role of somatosensory pain memories. In phantom limb pain, we propose that those patients who experienced intense pain prior to the amputation will later likely develop enhanced cortical reorganization and phantom limb pain. We show that cortical plasticity related to chronic pain can be reduced by behavioral interventions that provide feedback to the brain areas that were altered by somatosensory pain memories.     

神经病理性疼痛不同性质疼痛患者血清BDNF、TLR4表达水平差异及其诊断价值分析

摘要 目的：分析神经病理性疼痛（NP）不同性质疼痛患者血清脑源性神经生长因子（BDNF）、Toll受体4（TLR4）表达水平差异及其诊断价值。方法：选取2021年5月～2022年5月本院收治的80例NP患者和100例健康体检者作为研究对象,将NP患者其纳入NP组,将健康体检者纳入对照组,并参照神经病理性疼痛量表（NPS）区分NP组患者的疼痛性质（钝痛20例,不适感28例,深部痛17例,体表痛15例）,分别检测两组患者和NP组不同性质疼痛患者的血清BDNF、TLR4表达水平,采用双变量Spearman相关性检验血清BDNF、TLR4与NP不同性质疼痛的相关性,同时建立多因素Logistic模型,分析NP不同性质疼痛的影响因素,并比较其诊断效能。结果：与对照组比较,NP组血清BDNF表达水平较低,TLR4表达水平较高（P＜0.05）;NP钝痛、不适感、深部痛、体表痛的血清BDNF、TLR4表达水平比较（P＜0.05）;血清BDNF与NP钝痛、不适感、深部痛、体表痛呈负相关性,血清TLR4与NP钝痛、不适感、深部痛、体表痛呈正相关性（P＜0.05）;Logistic多因素分析结果显示,BDNF、TLR4均是NP钝痛、不适感、深部痛、体表痛的独立危险因素（P＜0.05）;血清BDNF、TLR4和BDNF+TLR4对NP钝痛、不适感、深部痛、体表痛的ACU均＞0.70。结论：血清BDNF、TLR4与钝痛、不适感、深部痛、体表痛等性质的NP均存在一定关联,在诊断不同NP性质方面具有较高的敏感性和特异性,有利于为临床治疗提供参考依据。     

腕踝针联合耳穴压豆治疗肝癌癌痛的疗效及对心理状态和血清疼痛介质的影响

摘要 目的：观察腕踝针联合耳穴压豆治疗原发性肝癌（PHC）癌痛的疗效及对心理状态和血清疼痛介质的影响。方法：选取湖南中医药大学第一附属医院2020年3月~2022年12月期间收治的PHC癌痛患者117例,按随机数字表法分为对照组和联合组,例数分别为58例和59例。两组患者均接受常规疼痛处理,对照组患者接受耳穴压豆治疗,联合组在对照组的基础上接受腕踝针治疗。对比两组疼痛缓解率、临床指标、心理状态和疼痛介质水平。结果：联合组的疼痛缓解率高于对照组（P<0.05）。联合组的数字疼痛法（NRS）评分低于对照组,止痛起效时间、每次疼痛持续时间短于对照组,爆发痛次少于对照组（P<0.05）。治疗后,两组焦虑自评量表（SAS）、抑郁自评量表（SDS）评分下降,且联合组低于对照组（P<0.05）。治疗后,两组5-羟色胺（5-HT）、P物质（SP）、前列腺素E₂（PGE₂）下降,且联合组低于对照组（P<0.05）。结论：腕踝针联合耳穴压豆治疗PHC癌痛,可有效减轻疼痛症状,降低血清疼痛介质水平,同时还可有效调节患者的心理状态,应用价值较好。     

经皮穴位电刺激联合常规镇痛对无痛人流术后宫缩痛镇痛效果及机制研究

摘要 目的：探讨经皮穴位电刺激联合常规镇痛对无痛人流术后宫缩痛镇痛效果及机制。方法：选择来我院行无痛人流患者100例。根据随机数字表法分为两组。对照组行术后常规镇痛治疗,同时在内关、合谷、三阴交最酸胀处黏贴电极但是不进行穴位刺激。观察组在术后常规镇痛基础上行经皮穴位电刺激治疗。对比不同时间点两组患者的机体一般情况、不同时间点两组患者的宫缩痛疼痛情况、T3时正性负性情绪量表评分、T3时血清P物质、前列腺素、5-羟色胺、β-内啡肽、强啡肽水平、T4点时的心理状态评分及满意度评分。结果：对照组T1、T2点时的BP、HR、RR、SpO₂明显较同组T0点低,对照组T3点与观察组T1、T2、T3点时BP、HR、RR、SpO₂与同组T0点对比无统计学意义（P>0.05）;对照组T1、T2点时的BP、HR、RR、SpO₂明显较观察组同时间点低（P<0.05）。T0点,两组VAS评分对比无统计学意义（P>0.05）;T1、T2、T3点时间,观察组的VAS评分明显较对照组低（P<0.05）;对照组T1、T2点的VAS评分明显较同组T0点高,观察组T1、T2、T3点的VAS评分明显较T0点低（P<0.05）。观察组的正性情绪明显较对照组高,负性情绪明显较对照组低（P<0.05）。观察组的血清P物质、前列腺素、5-羟色胺、β-内啡肽、强啡肽水平明显较对照组低（P<0.05）。观察组的心理状态评分明显较对照组低,满意度评分明显较对照组高（P<0.05）。结论：经皮穴位电刺激联合常规镇痛可明显改善无痛人流术后宫缩痛镇痛效果、患者心理状态及满意度,可能与其可降低血清P物质、前列腺素、5-羟色胺、β-内啡肽、强啡肽水平有关。     

The influence of spatial pulsed magnetic field application on neuropathic pain after tibial nerve transection in rat

The purpose of the study was to examine the influence of the spatial variable magnetic field (induction: 150–300?µT, 80–150?µT, 20–80?µT; frequency 40?Hz) on neuropathic pain after tibial nerve transection. The experiments were carried out on 64 male Wistar C rats. The exposure of animals to magnetic field was performed 1?d/20?min., 5?d/week, for 28?d. Behavioural tests assessing the intensity of allodynia and sensitivity to mechanical and thermal stimuli were conducted 1?d prior to surgery and 3, 7, 14, 21 and 28?d after the surgery. The extent of autotomy was examined. Histological and immunohistochemical analysis was performed. The use of extremely low-frequency magnetic fields of minimal induction values (20–80?µT/40?Hz) decreased pain in rats after nerve transection. The nociceptive sensitivity of healthy rats was not changed following the exposition to the spatial magnetic field of the low frequency. The results of histological and immunohistochemical investigations confirm those findings. Our results indicate that extremely low-frequency magnetic field may be useful in the neuropathic pain therapy.