Pain behaviour after castration of piglets; effect of pain relief with lidocaine and/or meloxicam

Behavioural responses and the effect of lidocaine and meloxicam on behaviour of piglets after castration were studied. A total of 144 piglets of 2 to 5 days of age were allocated to one of six treatments: castration (CAST), castration with lidocaine (LIDO), castration with meloxicam (MELO), castration with lidocaine and meloxicam (L + M), handling (SHAM) and no handling (NONE). Behaviour was observed for 5 days after the procedure, growth until weaning was recorded and characteristics of the castration wound noted. MELO piglets showed significantly (P < 0.05) more no pain-related behaviour than CAST and LIDO at the afternoon after castration, and were not significantly different from SHAM and NONE. LIDO piglets showed an increase (P < 0.001) in tail wagging, lasting for 3 days. This increase was not seen in L + M piglets. The occurrence of several behaviours changed with age, independent of treatment. A treatment effect on growth was not found. Wound healing was rapid in all treatments, but thickening of the heal was observed in several piglets, suggesting perturbation in the cicatrization process. Our study showed a pain-relieving effect of meloxicam after castration. Local anaesthesia resulted in piglets performing more tail wagging during the first few days after castration, which was prevented by administering meloxicam in combination with local anaesthesia.     

Effects of a local anaesthetic and NSAID in castration of piglets,on the acute pain responses,growth and mortality

The present study addresses the questions whether on-farm use of local anaesthesia with lidocaine leads to a reduction in pain responses during castration, and whether the non-steroidal anti-inflammatory drug meloxicam improves technical performance after castration of piglets. Five treatments were included in the study: (1) castration without anaesthesia or analgesia (CAST), (2) castration after local anaesthesia with lidocaine (LIDO), (3) castration after administration of meloxicam (MELO), (4) castration after lidocaine and meloxicam (L + M) and (5) sham castration (SHAM). To reduce litter influences, each treatment was present in each of the 32 litters (n = 32 per treatment). During castration, vocalizations were recorded continuously. Blood samples were collected 15 min before and 20 min after castration for determination of plasma levels of total cortisol, glucose, lactate and creatine kinase (CK). Mortality was registered and piglets were weighed several times to calculate growth. Several aspects of vocalizations during castration showed consistent and significantly different levels in CAST compared with LIDO, L + M and SHAM. CAST piglets squealed longer, louder and higher. Vocalizations of MELO piglets most resembled those of CAST. An increase in cortisol was seen in all treatments. However, in SHAM piglets this increase was significantly lower than in the other treatments. LIDO piglets showed a significantly smaller increase in plasma cortisol levels compared with CAST and MELO. L + M piglets differed significantly only from the SHAM group. Lactate levels differed significantly between LIDO and MELO, the level in LIDO being decreased after castration. In the other treatments an increase was measured. No treatment effects were found in plasma glucose and CK levels, nor in growth and mortality of the piglets. In conclusion, on the basis of vocalizations and plasma cortisol, local anaesthesia with lidocaine reduces pain responses in piglets during castration. A positive effect of meloxicam on technical performance was not found.     

Pre-natal stress amplifies the immediate behavioural responses to acute pain in piglets

Pre-natal stress (PNS) or undernutrition can have numerous effects on an individual''s biology throughout their lifetime. Some of these effects may be adaptive by allowing individuals to tailor their phenotype to environmental conditions. Here we investigated, in the domestic pig Sus scrofa, whether one possible consequence of a predicted adverse environment could be altered pain perception. The behavioural response of piglets to the surgical amputation (‘docking’) of their tail or a sham procedure was measured for 1 min in piglets born to mothers who either experienced mid-gestation social stress or were left undisturbed throughout pregnancy. A behavioural pain score was found to predict the docked status of piglets with high discriminant accuracy. Piglets exposed to PNS had a significantly higher pain score than controls, and for each litter of tail-docked piglets, the average pain score was correlated with mid-gestation maternal cortisol levels. The data presented here provide evidence that the experience of stress in utero can result in a heightened acute response to injury in early life. Speculatively, this may represent an adaptive alteration occurring as a consequence of a pre-natal ‘early warning’ of environmental adversity.     

Ear tagging in piglets: the cortisol response with and without analgesia in comparison with castration and tail docking

The objectives of the present study were to compare the cortisol response caused by ear tagging piglets with the distress caused by other known painful husbandry procedures (e.g. castration and tail docking) and to evaluate the effectiveness of analgesia with meloxicam to reduce the cortisol response caused by these procedures. In total, 210 male piglets were randomised to equal numbers (n=30) into one of seven groups: a control group which was only handled (H), an ear tagged group that received no analgesia (ET), an ear tagged group with analgesia (ETM), a castration group with no analgesia (C), a castration group with analgesia (CM), a tail-docked group with no analgesia (TD) and a tail-docked group with analgesia (TDM). The procedures were carried out on day 3 or 4 after farrowing. Five blood samples were taken from each piglet: 30 min before the respective procedure (baseline value), and 30, 60 min, 4 and 7 h after processing, to assess cortisol concentrations. Means as well as the area under the curve (AUC) value were analysed and the effective sizes of the procedures were established. At 7 h after the experimental treatment, cortisol concentrations had returned to base values in all groups. ET evoked a greater cortisol response than H piglets at 30 min (P<0.001) and 60 min (P=0.001). The cortisol response to ET was lower than C at 30 min (P=0.001) but did not differ significantly at the other sample times. The mean cortisol response was similar between ET and TD piglets over all sample times. Taking both intensity and duration of the cortisol response into account (AUC), ET evoked a greater response than TD. Analgesia (ETM) resulted in significantly lower cortisol levels than ET at 30 and 60 min post-procedure. Castration (C) provoked the highest cortisol response of all procedures; a significant analgesic effect (CM) was shown only at 4 h post-procedure. TD resulted in significantly higher cortisol levels than H piglets only at 30 min; analgesia (TDM) significantly reduced the cortisol response at 30 min. We conclude that ear tagging causes a dramatic increase in cortisol levels compared with handling alone in piglets, which suggests that this procedure causes substantial distress. However, further research is needed to confirm these results.     

He—Ne激光治疗带状疱疹神经痛

４３例带状疱疹病人随机分为Ｈｅ－Ｎｅ激光治疗组（２９例）及红外线对照组（１４例）,分别进行局部治疗（两组全身用药相同）。采用“６点行为疼痛测定法”对治疗期及治疗完成时的神经痛程度客观评分,经方差分析,治疗期及治疗后的结果显示激光治疗组的疗效明显优于对照组（ｐ＜０．０５～０．０１）;３月后随访,疱疹后神经痛的发生率两组相比亦有显著性差异（ｐ＜０．０１）。并对Ｈｅ－Ｎｅ激光在治疗带状疱疹神经痛的作用机理进行了讨论。     

Electric shock causes physiological stress responses in shore crabs,consistent with prediction of pain

Animal pain is defined by a series of expectations or criteria, one of which is that there should be a physiological stress response associated with noxious stimuli. While crustacean stress responses have been demonstrated they are typically preceded by escape behaviour and thus the physiological change might be attributed to the behaviour rather than a pain experience. We found higher levels of stress as measured by lactate in shore crabs exposed to brief electric shock than non-shocked controls. However, shocked crabs showed more vigorous behaviour than controls. We then matched crabs with the same level of behaviour and still found that shocked crabs had stronger stress response compared with controls. The finding of the stress response, coupled with previous findings of long-term motivational change and avoidance learning, fulfils the criteria expected of a pain experience.     

美洛昔康对Aβ诱导Alzheimer’s disease大鼠脑内炎症损伤的影响

目的：研究美洛昔康对β-淀粉样蛋白（Aβ）诱导的阿尔茨海默病（AD）模型大鼠脑内炎症损伤的保护作用,并探讨其抑制炎症作用的机制。方法：Aβ1-40海马注射建立AD大鼠模型。免疫组化法观察大鼠海马核因子κBp65（NF-κBp65）和星形胶质细胞（AS）胶质纤维酸性蛋白（GFAP）表达变化;Western-blot法测定大鼠皮层组织GFAP的表达;ELISA法检测大鼠皮层组织肿瘤坏死因子-α（TNF-α）水平变化;RT-PCR法检测大鼠海马组织白细胞介素-1β（IL-1β）mRNA的表达情况。结果：美洛昔康能抑制AD大鼠海马NF-κBp65和GFAP的表达;降低大鼠皮层TNF-α的含量;抑制AD大鼠海马IL-1βmRNA的表达。结论：美洛昔康通过减少AD模型大鼠海马、皮层组织GFAP表达,抑制AS的增生,降低NF-κBp65的活性,减少炎症因子TNF-α和IL-1β的水平,减轻脑内炎症反应。     

Behavioural responses of piglets to castration: the effect of piglet age

It has long been assumed that neonatal animals are less sensitive than older animals to pain, and this reasoning has been used to recommend that routine surgical procedures be performed at an early age. In this study we tested if vocal and other behavioural responses to castration increase with piglet age. Piglets (n=84) from 14 litters were assigned to one of six treatment groups: castration or sham castration at 3, 10 or 17 days of age. During the procedure castrated piglets produced high-frequency calls (>1000Hz) at more than three times the rate of piglets in the sham-castrate group. The rate of low-frequency (<1000Hz) calls was also higher for piglets in the castrate group. The rate of high-frequency calling was lower for the youngest pigs but there was no relationship between age and the effect of treatment for any of the vocal responses measured (i.e. no age by treatment interaction). During the first 2h after castration, castrated piglets spent more time sitting or standing and less time lying. During the subsequent 22h, castrated piglets spent marginally more time at the udder and less time lying down. Older piglets missed more nursings. However, the effect of castration did not vary with the age of the piglet for any measure. We conclude that while the factors affecting both the shams and the castrates (e.g. distress due to restraint) may vary with age, the pain of castration is not affected by age within the range of ages that we tested.     

The effect of two different doses of oral clodronate on pain in patients with bone metastases

The aim of this study was to evaluate the efficacy of low dose oral clodronate in palliation of pain arising from bone metastases (BM) and to determine the optimal oral clodronate dose which inhibits osteolysis caused by tumor. Fifty patients with bone pain caused by BM were included in this study. All were receiving antitumor chemotherapy or hormonal therapy. The patients were randomized into three groups according to the dose of clodronate. Groups A and B were given 800 mg/d and 1600 mg/d of oral clodronate respectively for 3 months. Group C was the control group. The effect of clodronate in pain palliation was evaluated with pain score, performance status, and changes in analgesic use. The effect on osteolysis was examined with urinary calcium, hydroxyproline (OHP) and serum cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) levels. Group A contained 16 patients, and groups B and C contained 17 patients each. After 3 months use of oral clodronate, significant decrease in the pain score of groups A and B was noted when, compared to group C (P=0.024 andP=0.007, respectively) The analgesic use of 11 patients in group A (69%) and 8 patients in group B (47%) was decreased, but only the decrease in group A was statistically significant (P=0.038). Pain score increased in 5 patients in group C (29%), and 3 patients in groups A (19%) and B (18%) each. Urinary calcium, OHP and serum ICTP levels increased in group C and decreased in groups A and B, but only the decrease of urinary calcium levels of group B was significant (P=0.003). In conclusion, low dose (800 mg/d) oral clodronate seems to be as effective as standard dose (1600 mg/d) in palliation of bone pain secondary to BM.     

Interaction of local anesthetics with the K+ channel pore domain

Local anesthetics and related drugs block ionic currents of Na⁺, K⁺ and Ca²⁺ conducted across the cell membrane by voltage-dependent ion channels. Many of these drugs bind in the permeation pathway, occlude the pore and stop ion movement. However channel-blocking drugs have also been associated with decreased membrane stability of certain tetrameric K⁺ channels, similar to the destabilization of channel function observed at low extracellular K⁺ concentration. Such drug-dependent stability may result from electrostatic repulsion of K⁺ from the selectivity filter by a cationic drug molecule bound in the central cavity of the channel. In this study we used the pore domain of the KcsA K⁺ channel protein to test this hypothesis experimentally with a biochemical assay of tetramer stability and theoretically by computational simulation of local anesthetic docking to the central cavity. We find that two common local anesthetics, lidocaine and tetracaine, promote thermal dissociation of the KcsA tetramer in a K⁺-dependent fashion. Docking simulations of these drugs with open, open-inactivated and closed crystal structures of KcsA yield many energetically favorable drug-channel complexes characterized by nonbonded attraction to pore-lining residues and electrostatic repulsion of K⁺. The results suggest that binding of cationic drugs to the inner cavity can reduce tetramer stability of K⁺ channels.     

Comparing the local dynamic stability of trunk movements between varsity athletes with and without non-specific low back pain

The local dynamic stability of trunk movements, quantified using the maximum Lyapunov exponent (λ_max), can provide important information on the neuromuscular control of spine stability during movement tasks. Although previous research has displayed the promise of this technique, all studies were completed with healthy participants. Therefore the goal of this study was to compare the dynamic stability of spine kinematics and trunk muscle activations, as well as antagonistic muscle co-contraction, between athletes with and without low back pain (LBP). Twenty interuniversity varsity athletes (10 LBP, 10 healthy controls) were recruited to participate in the study. Each participant completed a repetitive trunk flexion task at 15 cycles per minute, both symmetrically and asymmetrically, while trunk kinematics and muscular activity (EMG) were monitored. The local dynamic stability of low back EMG was significantly higher (lower λ_max) in healthy individuals (p=0.002), whereas the dynamic stability of kinematics, the dynamic stability of full trunk system EMG, and the amount of antagonistic co-contraction were significantly higher when moving asymmetrically (p<0.05 for all variables). Although non-significant, kinematic and trunk system EMG stability also tended to be impaired in LBP participants, whereas they also tended to co-contract their antagonist muscles more. This study provides evidence that Lyapunov analyses of kinematic and muscle activation data can provide insight into the neuromuscular control of spine stability in back pain participants. Future research will repeat these protocols in patients with higher levels of pain, with hopes of developing a tool to assess impairment and treatment effectiveness in clinical and workplace settings.     

The effect of stimulus number on the stability of responses for an extensive heat pain test

Background.?The use of relatively lower stimulus presentation numbers in quantitative sensory testing may influence the computation accuracy of participants’ discriminability. The minimum trial number for obtaining a stabilized participant discrimination ability was determined.

Materials and methods.?Twelve participants’ ability to discriminate between noxious heat stimuli pairs (45°C/46°C, 46°C/47°C, and 47°C/48°C) was assessed using a six-category confidence rating scale. Heat stimuli were administered to the forearm. Two conditions with presentation numbers of 17 trials per stimulus (representing the median number of trials in previous studies) and 40 trials per stimulus (used in a previous study with a similar protocol) were used.

Results and discussion.?Participants’ discriminability stabilized at approximately the 20th trial based on the lowest frequency of indeterminate and non-model conforming results under both conditions. A simple linear regression model showed a statistically significant positive relationship between discriminability for the two conditions (slope?=?0.65, p?<?0.001; constant?=?0.33, p?=?0.02; r^2?=?0.51). As a rule of thumb, approximately 20 trials per stimulus intensity could be used to obtain a stabilized discriminability outcome.     

Interaction of spin-labeled local anesthetics with the sodium channel of squid axon membranes

Summary The effects of spin-labeled local anesthetics on sodium currents of internally perfused squid axons were studied using the voltage-clamp technique. Internal application (10 m) of the most potent spin-labeled local anesthetic used in this study produced a small initial block of sodium currents. However, after sixty repetitive pulses (to +80 mV) given at 1 Hz, the sodium currents were drastically reduced. In addition to this frequency-dependent phenomenon, the anesthetic effect on the sodium currents was also sensitive to the voltage of the pulses. Both the frequency- and voltage-dependent properties remained intact after removal of sodium inactivation with pronase. The recovery of sodium currents from this frequency-dependent anesthetic effect followed a single exponential curve with a surprisingly long time constant of about 10 min. Such a long recovery time, which is longer than any known sodium inactivation process, led us to suggest that the recovery process represents the dissociation of drug molecules from their binding sites. We have also found that increasing hydrophobic character of the homologues series of spin-labeled local anesthetics enhances the frequency- and voltage-dependent block of sodium currents. This effect strongly suggests that hydrophobic interaction is an integral component of the binding site. These probes with their selective effects on the sodium currents, are expected to be highly useful in studying the molecular structure of the sodium channels.     

The interaction of local anesthetics with the ryanodine receptor of the sarcoplasmic reticulum

The effects of various local anesthetics (LAs) on the skeletal muscle ryanodine receptor were tested. The LAs were divided into three categories according to their effects on the binding of ryanodine to the junctional sarcoplasmic reticulum membranes. Ryanodine binding was assayed in the presence of 0.2 m NaCl and 10 m CaCl₂. Tetracaine and dibucaine inhibit the binding with half-maximal inhibition (CI₅₀) of 0.12 and 0.25 mm, respectively, while inhibition by benzocaine and procaine occurs with CI₅₀ of about 10-fold higher. Lidocaine, its analogue QX-314, and prilocaine, on the other hand, stimulate the binding up to fourfold with half-maximal stimulation occurring with about 2 mm of the drugs. Lidocaine increases both the receptor affinity for ryanodine by about fivefold and the rate of ryanodine association with its binding site by about 10-fold.Tetracaine interacts with the ryanodine receptor in a non-competitive fashion with respect to ryanodine but it competes with lidocaine for its binding site, suggesting the existence of a single site for the inhibitory and stimulatory LA.     

Impact of dietary protein on microbiota composition and activity in the gastrointestinal tract of piglets in relation to gut health: a review

In pigs, the microbial ecosystem of the gastrointestinal tract (GIT) is influenced by various factors; however, variations in diet composition have been identified as one of the most important determinants. Marked changes in fermentation activities and microbial ecology may occur when altering the diet, for example, from milk to solid feed during weaning. In that way, access of pathogens to the disturbed ecosystem is alleviated, leading to infectious diseases and diarrhea. Thus, there is increasing interest in improving intestinal health by use of dietary ingredients suitable to beneficially affect the microbial composition and activity. For example, fermentable carbohydrates have been shown to promote growth of beneficial Lactobacillus species and bifidobacteria, thereby enhancing colonization resistance against potential pathogens or production of short-chain fatty acids, which can be used as energy source for epithelial cells. On the other hand, fermentation of protein results in the production of various potentially toxic products, such as amines and NH₃, and is often associated with growth of potential pathogens. In that way, excessive protein intake has been shown to stimulate the growth of potentially pathogenic species such as Clostridium perfringens, and to reduce fecal counts of beneficial bifidobacteria. Therefore, it seems to be a promising approach to support growth and metabolic activity of the beneficial microbiota by developing suitable feeding strategies. For example, a reduction of dietary CP content and, at the same time, dietary supplementation with fermentable carbohydrates have proven to successfully suppress protein fermentation. In addition, the intestinal microbiota seems to be sensible to variations in dietary protein source, such as the use of highly digestible protein sources may reduce growth of protein-fermenting and potentially pathogenic species. The objective of the present review is to assess the impact of dietary protein on microbiota composition and activity in the GIT of piglets. Attention will be given to studies designed to determine the effect of variations in total protein supply, protein source and supplementation of fermentable carbohydrates to the diet on composition and metabolic activity of the intestinal microbiota.     

On the specific and unspecific effects of a polymeric glucomannan mycotoxin adsorbent on piglets when fed with uncontaminated or with Fusarium toxins contaminated diets

Abstract

A 35-day feeding experiment was performed with weaned piglets (initial live weight of 7.7±1 kg) to test the effects of a Fusarium toxin contamination of the diet (4.44 mg deoxynivalenol [DON] per kg diet) compared to an uncontaminated control diet. Both diet types were fed either unsupplemented or supplemented with a polymeric glucomannan mycotoxin adsorbent (GMA) to examine the claimed efficacy of detoxification of this feed additive through unspecific performance parameters and the specific proof of the prevention of DON absorption. Feeding of the mycotoxin-contaminated diets resulted in a decrease in feed intake and live weight gain by 28% and 14% when compared to the control group. These effects were independent of GMA addition. Based on the lack of significant interactions between diet mycotoxin-contamination and GMA supplementation for the performance data, and because of the inefficiency of GMA in decreasing DON absorption, it was concluded that the supplementation of DON-contaminated piglet diets with GMA cannot be recommended as an effective tool for alleviation of adverse DON effects.     

The effect of local or general anesthesia on the physiology and behavior of tail docked pigs

Tail docking of pigs is a routine procedure on farms to help control tail-biting behavior; however, docking can cause pain. The objective of this research was to evaluate the effect of local or general anesthesia on the physiology (experiment 1) and behavior (experiment 2) of tail docked pigs. Pigs were allocated to one of six treatment groups: (i) sham docking (CON); (ii) docking using conventional cutting (CUT) with side-cutting pliers; (iii) CUT docking plus local anesthesia injected immediately before docking (LA); (iv) CUT docking plus short-acting local anesthesia applied topically to the tail wound (SHORT); (v) CUT docking plus long-acting anesthesia applied topically to the tail wound (LONG) and (vi) CUT docking while the pig was anesthetized with carbon dioxide gas (CO(2)). In experiment 1, blood samples were collected from pigs (10 pigs per treatment) before and 30, 60 and 120 min after docking to measure leukocyte counts and percentages and cortisol concentrations. In experiment 2, the above treatments were repeated (10 pigs per treatment); the percentage of stress vocalizations were recorded during the administration of the treatments and behavior was recorded for up to 120 min after docking or handling. All pigs were weighed before and 24 h after docking and wound healing was recorded until weaning. The neutrophil/lymphocyte ratio was greater (P < 0.05) in CUT, LA, SHORT and LONG compared with CON pigs. At 30 min, cortisol concentrations were greater (P < 0.05) in CUT, LA, LONG and CO(2) compared with CON pigs. Cortisol concentrations did not differ (P > 0.05) between SHORT and CON pigs 30 min after docking. Cortisol concentrations did not differ (P > 0.05) among pigs given pain relief at the time of docking compared with pigs' docked without pain relief. Body weight change and wound scores did not differ (P > 0.05) among treatments. The percentage of stress vocalizations increased (P < 0.05) in CUT, SHORT and LONG, but not in CON, LA and CO(2) pigs in response to docking or handling. The percentage of time pigs spent lying without contact after docking tended to be greater (P = 0.06) in CUT pigs compared with all other docking treatments and CON pigs. In this study, none of the anesthesia treatments tested were effective at significantly changing the physiological or behavioral response to tail docking in pigs.     

Comparing the efficacy of pain managements after total hip arthroplasty: A network meta-analysis

The aim of our current study is to compare efficiency of various interventions implemented for pain management after total hip arthroplasty (THA). PubMed and EMBASE were searched for randomized clinical trials (RCTs) reporting the pain scales for evaluate the efficacy of pain control after THA including at least one pair of direct control groups. Pain scale values and the associated 95% credible interval (CrI) were used to describe efficacy. Surface under the cumulative ranking curve (SUCRA) of each means of pain control was calculated to compare the relative ranking of different interventions. Thirty-five eligible literatures were involved in data analysis. The interventions for postoperative pain management we examined were psoas compartment block (PCB), posterior nerve block (PNB), fascia iliaca block (FIB), periarticular injection (PAI), femoral nerve block (FNB), lumbar plexus block (LPB), spinal anesthesia (SA), epidural analgesia (EPI), intrathecal morphine (IA), intravenous patient-controlled analgesia (IV-PCA), patient-controlled analgesia (PCA), onsteroidal anti-inflammatory drug (NSAID), local infiltration analgaesia (LIA), and reverse LIA (rLIA). In 0 to 6 hours analysis, patients under SA were found to have significantly lower pain score and SA was ranked the best. In 6 to 12 hours analysis, SA was found to be significantly more effective than other interventions and its SUCRA was the highest. No intervention showed a significant effect on reducing pain score for 12 to 24 hours and 24 to 48 hours after THA. SA is the best intervention to reduce THA postoperative pain in the first 24 hours. LPB is a better choice to reduce pain 12 to 48 hours after THA.