The role of vanilloid receptor type 1 (TRPV1) in hyperalgesia related to bovine digital dermatitis.

Bovine digital dermatitis is a contagious and chronic disease affecting the digits of dairy cattle worldwide. Tissue degradation may alter ionic channels and further activate vanilloid channels, more specifically the vanilloid receptor type 1 (TRPV1) that can generate and modulate hyperalgesia in cows affected with bovine digital dermatitis. The aim of this pilot study was to identify and quantify TRPV1 channels in dairy cows presenting with different stages of bovine digital dermatitis and compare these data according to the disease evolution and degree of hyperalgesia described in previous studies. Biopsies were taken from 15 lactating Holstein cows (23 lesions), and immunochemistry was performed to identify the number of TRPV1 fibers in the 4 M-stages of digital dermatitis and the control group. This pilot study had 5 experimental groups, M1 (5 samples), M2 (5 samples), M3 (4 samples), M4 (4 samples), and the control group (5 samples), with inclusion criteria was the presence of a bovine digital dermatitis lesion in at least one digit. The pilot results demonstrate an increase in expression of TRPV1 receptors in group M4 in comparison with the other groups. Bovine digital dermatitis may cause an increase in expression of TRPV1 receptors in the chronic stages of the disease, possibly contributing to the hyperalgesia described in affected animals; nevertheless, further research is needed to define this relation.

Determination of acute tolerance and hyperalgesia to remifentanil constant rate infusion in dogs undergoing sevoflurane anaesthesia.

OBJECTIVE: To determine if acute opioid tolerance (AOT) or opioid-induced hyperalgesia (OIH) could develop and limit the remifentanil-induced reduction in the sevoflurane minimum alveolar concentration (MAC). The response to mechanical nociceptive threshold (MNT) was evaluated and related to OIH. STUDY DESIGN: A crossover, randomized, experimental animal study. ANIMALS: A total of nine Beagle dogs. METHODS: The dogs were anaesthetized with sevoflurane in 50% oxygen. Baseline sevoflurane MAC was measured (MACb1). Remifentanil (0.3 µg kg-1 minute-1) or 0.9% saline constant rate infusion (CRI) was administered intravenously (IV). Sevoflurane MAC was determined 20 minutes after CRI was initiated (MACpostdrug1), 30 minutes after MACpostdrug1 determination (MACpostdrug2) and after 1 week (MACb2). The MNT was determined at baseline (before anaesthesia), 3 and 7 days after anaesthesia. An increase of MACpostdrug2 ≥0.25% compared to MACpostdrug1 was considered evidence of AOT. A decrease in MNT at 3 and 7 days or an increase in MACb2 or both with respect to MACb1 were considered evidence of OIH. RESULTS: Remifentanil CRI reduced sevoflurane MACpostdrug1 by 43.7% with respect to MACb1. MACpostdrug2 was no different from MACpostdrug1 with the saline (p = 0.62) or remifentanil (p = 0.78) treatments. No significant differences were observed in the saline (p = 0.99) or remifentanil (p = 0.99) treatments between MACb1 and MACb2, or for MNT values between baseline, 3 and 7 days. CONCLUSION AND CLINICAL RELEVANCE: In dogs, under the study conditions, remifentanil efficacy in reducing sevoflurane MAC did not diminish in the short term, suggesting remifentanil did not induce AOT. Hyperalgesia was not detected 3 or 7 days after the administration of remifentanil. Contrary to data from humans and rodents, development of AOT or OIH in dogs is not supported by the findings of this study.

Gentiopicroside Ameliorates Diabetic Peripheral Neuropathy by Modulating PPAR- Γ/AMPK/ACC Signaling Pathway.

BACKGROUND/AIMS: Gentiopicroside is promising as an important secoiridoid compound against pain. The present study aimed to investigate the analgesic effect and the probable mechanism of Gentiopicroside on Diabetic Peripheral Neuropathy (DPN), and to figure out the association among Gentiopicroside, dyslipidemia and PPAR- γ/AMPK/ACC signaling pathway. METHODS: DPN rat models were established by streptozotocin and RSC96 cells were cultured. Hot, cold and mechanical tactile allodynia were conducted. Blood lipids, nerve blood flow, Motor Nerve Conduction Velocity (MNCV) and Sensory Nerve Conduction Velocity (SNCV) were detected. Gene and protein expression of PPAR- γ/AMPK/ACC pathway was analyzed by reverse transcription-quan titative polymerase chain reaction (RT-qPCR) and Westernblot. Besides, PPAR-γ antagonist GW9662 and agonist rosiglitazone, AMPK antagonist compound C and activator AICAR as well as ACC inhibitor TOFA were used to further confirm the relationship between PPAR-γ and AMPK. RESULTS: The results demonstrated that Gentiopicroside markedly ameliorated hyperalgesia with prolonged paw withdrawal latency to heat and cold stimuli and fewer responses to mechanical allodynia compared with DPN model group. Gentiopicroside regulated dyslipidemia, enhanced nerve blood flow and improved MNCV as well as SNCV. Gentiopicroside suppressed ACC expression through the activation of AMPK and PPAR-γ mediated the activation of AMPK and subsequent inhibition of ACC expression. CONCLUSION: In conclusion, the present study demon strated that Gentiopicroside exerted nerve-protective effect and attenuated experimental DPN by restoring dyslipidmia and improved nerve blood flow through regulating PPAR-γ/AMPK/ACC signal pathway. These results provided a promising potential treatment of DPN.

Long-term and trans-generational effects of neonatal experience on sheep behaviour.

Early life experiences can have profound long-term, and sometimes transgenerational, effects on individual phenotypes. However, there is a relative paucity of knowledge about effects on pain sensitivity, even though these may impact on an individual's health and welfare, particularly in farm animals exposed to painful husbandry procedures. Here, we tested in sheep whether neonatal painful and non-painful challenges can alter pain sensitivity in adult life, and also in the next generation. Ewes exposed to tail-docking or a simulated mild infection (lipopolysaccharide (LPS)) on days 3­4 of life showed higher levels of pain-related behaviour when giving birth as adults compared with control animals. LPS-treated ewes also gave birth to lambs who showed decreased pain sensitivity in standardized tests during days 2­3 of life. Our results demonstrate long-term and trans-generational effects of neonatal experience on pain responses in a commercially important species and suggest that variations in early life management can have important implications for animal health and welfare.

Do psychological and physiological stressors alter the acute pain response to castration and tail docking in lambs?

OBJECTIVE: To investigate whether events that may be stressful to young lambs, including simulated infection or social isolation, modulate pain experienced by lambs following castration and tail docking (C/D). STUDY DESIGN: Randomised, controlled, prospective study. ANIMALS: Fifty male lambs born to 46 second-parity Mule ewes. METHODS: Lambs were allocated randomly to one of four groups, experiencing either a potential stressor or handling on day 2 after birth, followed by C/D or handling only on day 3. Quantitative sensory testing (QST) data [mechanical nociceptive thresholds (MNT), Semmes Weinstein filaments (SW), response to cold] and serum cortisol concentration were measured at time points after application of treatments to lambs on days 2 and 3 after birth. The treatment groups were LPS, injection of bacterial lipopolysaccharide IV on day 2, C/D on day 3; ISOL, isolation from the dam for 10 minutes on day 2, C/D on day 3; CAST, handling only on day 2, C/D on day 3; CONT, handled only on days 2 and 3. RESULTS: Castration and tail docking caused transient hypoalgesia as measured by MNT and SW. Simulated infection and isolation caused hyperalgesia 3 hours after application, indicated by a reduction in MNT, however they did not alter the pain response to C/D compared to lambs in the CAST group. Injection of LPS and C/D caused increased serum cortisol concentration. The magnitude of the cortisol response to C/D was not altered by prior exposure to either LPS or isolation. CONCLUSIONS AND CLINICAL RELEVANCE: LPS and isolation did not modulate the response to C/D but did cause hyperalgesia. This highlights the importance of flock health management and husbandry techniques to reduce the incidence of either systemic infection or psychological stressors in young lambs.

Comparison of Nociceptive Effects of Buprenorphine, Firocoxib, and Meloxicam in a Plantar Incision Model in Sprague-Dawley Rats.

Due to their reduced frequency of dosing and ease of availability, NSAIDs are generally preferred over opioids for rodent analgesia. We evaluated the efficacy of the highly COX2-selective NSAID firocoxib as compared with meloxicam and buprenorphine for reducing allodynia and hyperalgesia in rats in a plantar incision model of surgical pain. After a preliminary pharmacokinetic study using firocoxib, Sprague-Dawley rats (n = 12 per group, 6 of each sex) were divided into 6 groups: no surgery (anesthesia only), saline (surgery but no analgesia), buprenorphine (0.05 mg/kg SC every 8 h), meloxicam (2 mg/kg SC every 24 h), and 2 dosages of firocoxib (10 and 20 mg/kg SC every 24 h). The nociception assays were performed by using von Frey and Hargreaves methodology to test mechanical allodynia and thermal hyperalgesia. These assays were performed at 24 h before and at 20, 28, 44, and 52 h after start of surgery. None of the analgesics used in this study produced significantly different responses in allodynia or hyperalgesia from those of saline-treated rats. In the Hargreaves assay, female saline-treated rats experienced significantly greater hyperalgesia than did males. These findings add to a growing body of literature suggesting that commonly used dosages of analgesics may not provide sufficient analgesia in rats experiencing incisional pain.

Transcription factor Sp4 is required for hyperalgesic state persistence.

Understanding how painful hypersensitive states develop and persist beyond the initial hours to days is critically important in the effort to devise strategies to prevent and/or reverse chronic painful states. Changes in nociceptor transcription can alter the abundance of nociceptive signaling elements, resulting in longer-term change in nociceptor phenotype. As a result, sensitized nociceptive signaling can be further amplified and nocifensive behaviors sustained for weeks to months. Building on our previous finding that transcription factor Sp4 positively regulates the expression of the pain transducing channel TRPV1 in Dorsal Root Ganglion (DRG) neurons, we sought to determine if Sp4 serves a broader role in the development and persistence of hypersensitive states in mice. We observed that more than 90% of Sp4 staining DRG neurons were small to medium sized, primarily unmyelinated (NF200 neg) and the majority co-expressed nociceptor markers TRPV1 and/or isolectin B4 (IB4). Genetically modified mice (Sp4+/-) with a 50% reduction of Sp4 showed a reduction in DRG TRPV1 mRNA and neuronal responses to the TRPV1 agonist-capsaicin. Importantly, Sp4+/- mice failed to develop persistent inflammatory thermal hyperalgesia, showing a reversal to control values after 6 hours. Despite a reversal of inflammatory thermal hyperalgesia, there was no difference in CFA-induced hindpaw swelling between CFA Sp4+/- and CFA wild type mice. Similarly, Sp4+/- mice failed to develop persistent mechanical hypersensitivity to hind-paw injection of NGF. Although Sp4+/- mice developed hypersensitivity to traumatic nerve injury, Sp4+/- mice failed to develop persistent cold or mechanical hypersensitivity to the platinum-based chemotherapeutic agent oxaliplatin, a non-traumatic model of neuropathic pain. Overall, Sp4+/- mice displayed a remarkable ability to reverse the development of multiple models of persistent inflammatory and neuropathic hypersensitivity. This suggests that Sp4 functions as a critical control point for a network of genes that conspire in the persistence of painful hypersensitive states.

Allatostatin C modulates nociception and immunity in Drosophila.

Bacterial induced inflammatory responses cause pain through direct activation of nociceptive neurons, and the ablation of these neurons leads to increased immune infiltration. In this study, we investigated nociceptive-immune interactions in Drosophila and the role these interactions play during pathogenic bacterial infection. After bacterial infection, we found robust upregulation of ligand-gated ion channels and allatostatin receptors involved in nociception, which potentially leads to hyperalgesia. We further found that Allatostatin-C Receptor 2 (AstC-R2) plays a crucial role in host survival during infection with the pathogenic bacterium Photorhabdus luminescens. Upon examination of immune signaling in AstC-R2 deficient mutants, we demonstrated that Allatostatin-C Receptor 2 specifically inhibits the Immune deficiency pathway, and knockdown of AstC-R2 leads to overproduction of antimicrobial peptides related to this pathway and decreased host survival. This study provides mechanistic insights into the importance of microbe-nociceptor interactions during bacterial challenge. We posit that Allatostatin C is an immunosuppressive substance released by nociceptors or Drosophila hemocytes that dampens IMD signaling in order to either prevent immunopathology or to reduce unnecessary metabolic cost after microbial stimulation. AstC-R2 also acts to dampen thermal nociception in the absence of infection, suggesting an intrinsic neuronal role in mediating these processes during homeostatic conditions. Further examination into the signaling mechanisms by which Allatostatin-C alters immunity and nociception in Drosophila may reveal conserved pathways which can be utilized towards therapeutically targeting inflammatory pain and chronic inflammation.

Carprofen and buprenorphine prevent hyperalgesia in a model of inflammatory pain in cats.

A model of nociceptive threshold determination was developed for evaluation of NSAID analgesia in cats. In a crossover study, eight cats received carprofen (4 mg/kg), buprenorphine (0.01 mg/kg) or saline (0.3 ml) subcutaneously before intradermal kaolin injection on the antebrachium to induce mild inflammation. Pressure thresholds were measured at the injected site using blunt-ended pins advanced by manual inflation of a bladder within a bracelet. Bladder pressure was recorded as threshold (PT) at the behavioural end point. Baseline PT were recorded before kaolin injection (time 0). PT was measured at 2-10 h intervals for 52 h. PT below the lower 95% confidence interval (CI) of baseline values indicated hyperalgesia. After saline, hyperalgesia was detected from 2-6 h, 22-26 h, and at 30 and 36 h. After carprofen, PT remained within the 95% CI. After buprenorphine, PT remained within the 95% CI except at 2h. Carprofen and to some extent buprenorphine, prevented inflammatory hyperalgesia.

Pain assessment following experimental maxillofacial surgical procedure in sheep.

The aim of this study was to investigate the severity and duration of postoperative pain and hyperalgesia in sheep undergoing mandibular reconstructive surgery. Stimulus-evoked sensitivity at the surgical site and an area remote from injury, the ipsilateral and contralateral forelimbs, was measured as objective indicators of altered pain processing in adult female sheep (n = 7). Responses were recorded before surgery and one, two, three, seven and 14 days afterwards. Concentrations of the acute-phase protein haptoglobin were measured in serum as a marker of inflammation before and at one and seven days after surgery. A significant decrease in forelimb mechanical withdrawal thresholds (secondary hyperalgesia) and response thresholds to punctate stimulation of the area surrounding the surgical incision (allodynia) was detected one day after surgery and persisted for at least three days, despite intra- and postoperative analgesic treatment. Concentrations of haptoglobin were significantly increased one day post-surgery, indicating the presence of a significant acute inflammatory response, and returned to pre-surgical concentrations by seven days. These data provide a deeper insight into understanding the impact of surgery in experimental animals, and may assist in formulating more effective analgesic and antihyperalgesic treatment regimens postoperatively.

Influence of nifedypine on the hyperalgesic action of duodenal distention in sheep.

The aim of this study was to determine the influence of nifedypine--competitive antagonist of voltage-gated dependent L-type Ca2+ channels (VGCCs)--on inhibition of reticulo-ruminal motility, heart beats, respiratory rates and other nociceptive behavior symptoms caused by duodenal distention (DD). The animals, which were under general anesthesia, had duodenal and ruminal fistulas and intracerebroventriculary (i.c.v.) cannulas inserted into the lateral ventricle. Reticulo-ruminal contractions were recorded mechanographically using an electronic tensometer. The frequency of reticulo-ruminal contractions was determined by the number of mechanograms with 5 min intervals prior to and after DD (for 180 min). The duodenal distention was performed using a rubber balloon (10 cm length), which was inserted via the duodenal fistula and filled with 40 ml water. Five min DD caused immediate and almost complete inhibition of reticulo-ruminal contractions, nociceptive behavior symptoms, tachycardia and hyperventilation. Nifedypine per se did not change the reticulo-ruminal motility, general behavior or clinical symptoms; however, doses of 1 and 2 mg of nifedypine in toto infused i.c.v 10 minutes before DD prevented all signs of reticulo-ruminal disorders, as well as the general nociceptive behavior. Nifedypine inhibited particularly clinical symptoms such as tachycardia and hyperventilation. The observed antinociceptive action of VGCCs type-L blockers suggests that these channels play a crucial role in the modulation of acute visceral hyperalgesia. Nifedipine can be useful in controlling acute visceral pain associated, for example, with different kinds of colic.

Hyperalgesia-type response reveals no difference in pain-related behavior between Wistar and Sprague-Dawley rats.

The experience of pain is variable among certain cultures, ethnical groups and among individuals. This variability can be explained by environmental influence, genetic predisposition and plasticity of the existing neuronal pathways. The purpose of this study was to examine a strain-related difference in pain sensitivity between Wistar and Sprague-Dawley rats strains and if there was a difference, could it be overcomes with the robust test. Mechanical sensitivity e.g. existence of paw withdrawal and complex hyperalgesia-type response after needle stimuli has been measured. Both hindpaws (middle, medial and lateral part) were stimulated randomly in appropriate intervals. The results did not demonstrate statistically significant strain difference in pain sensitivity, except in the lateral part of the hindpaw where Sprague-Dawley rats were more sensitive. This data emphasize the importance of selecting a robust behavior test that will be used in investigation of peripheral nerve injury and in neuropathic pain research.

Metamizole (dipyrone) effects on sevoflurane requirements and postoperative hyperalgesia in rats.

Unlike non-steroidal anti-inflammatory drugs (NSAIDs), metamizole has poor anti-inflammatory effects; and is suitable for models where analgesia, but not anti-inflammatory effects, is desirable. Like opioids, these drugs produce perioperative analgesia while reducing anaesthetic requirements, but it remains unclear whether they may develop tolerance or hyperalgesia, and thus decrease in analgesic efficacy. The aim was to determine whether tolerance or hyperalgesia to metamizole occurred in rats, and whether the sevoflurane minimum alveolar concentration (MAC) was affected. In a randomized, prospective, controlled study, male Wistar rats ( n = 8 per group) were administered metamizole (300 mg/kg, day 4). Previously, the following treatments were provided: daily metamizole for four days (0-3), morphine (10 mg/kg; positive control, day 0 only) or saline (negative control). The main outcome measures were mechanical (MNT) and warm thermal (WNT) nociceptive quantitative sensory thresholds. The baseline sevoflurane MAC and the reduction produced by the treatments were also determined. The mean (SD) baseline MAC [2.4(0.2)%vol] was decreased by morphine and metamizole by 45(11)% and 33(7)% ( P = 0.000, both), respectively. Baseline MNT [35.4(4.5) g] and WNT [13.2(2.4) s] were decreased by morphine and metamizole: MNT reduction of 22(6)% ( P = 0.000) and 22(7)% ( P = 0.001), respectively and WNT reduction of 34(14)% ( P = 0.000) and 24(13)% ( P = 0.001). The baseline MAC on day 4 was neither modified by treatments nor the MAC reduction produced by metamizole (days 0 and 4; P > 0.05). In conclusion, repeated metamizole administration may produce hyperalgesia, although it may not modify its anaesthetic sparing effect. The clinical relevance of this effect in painful research models requiring prolonged analgesic therapy warrants further investigation.

Role of ketoprofen in the modulation of hyperalgesia associated with lameness in dairy cattle.

Forty lame dairy cows were randomly assigned to receive a course of either the non-steroidal anti-inflammatory drug ketoprofen, or sterile saline, together with conventional treatment for lameness. The effect of the ketoprofen was measured by using locomotion scoring and by testing the cows' nociceptive threshold over a period of 28 days. The locomotion score of all the cows improved but ketoprofen had no significant effect on this change. However, in the cows that received ketoprofen the hyperalgesia associated with lameness, recorded using a nociceptive threshold test, was significantly modulated on days 3, 8 and 28 after their initial examination, drug administration and treatment of lesions.

Novel Noxipoint Therapy versus Conventional Physical Therapy for Chronic Neck and Shoulder Pain: Multicentre Randomised Controlled Trials.

As chronic pain affects 115 million people and costs $600B annually in the US alone, effective noninvasive nonpharmacological remedies are desirable. The purpose of this study was to determine the efficacy and the generalisability of Noxipoint therapy (NT), a novel electrotherapy characterised by site-specific stimulation, intensity-and-submodality-specific settings and a immobilization period, for chronic neck and shoulder pain. Ninety-seven heavily pretreated severe chronic neck/shoulder pain patients were recruited; 34 and 44 patients were randomly allocated to different treatment arms in two patient-and-assessor-blinded, randomised controlled studies. The participants received NT or conventional physical therapy including transcutaneous electrical nerve stimulation (PT-TENS) for three to six 90-minute sessions. In Study One, NT improved chronic pain (-89.6%, Brief Pain Inventory, p < 0.0001, 95% confidence interval), function (+77.4%, range of motion) and quality of life (+88.1%) at follow-up (from 4 weeks to 5 months), whereas PT-TENS resulted in no significant changes in these parameters. Study Two demonstrated similar advantages of NT over PT-TENS and the generalisability of NT. NT-like treatments in a randomised rat study showed a similar reduction in chronic hypersensitivity (-81%, p < 0.01) compared with sham treatments. NT substantially reduces chronic neck and shoulder pain, restores function, and improves quality of life in a sustained manner.

Analgesic and antihyperalgesic effects of dipyrone, meloxicam or a dipyrone-meloxicam combination in bitches undergoing ovariohysterectomy.

The analgesic and antihyperalgesic effects of dipyrone, meloxicam or a dipyrone-meloxicam combination were compared in dogs undergoing elective ovariohysterectomy. In a double-blinded, prospective, randomised design, 40 bitches premedicated with intramuscular pethidine (4 mg/kg) and anaesthetised with isoflurane received one of four intravenous treatments (n = 10 per group) before ovariohysterectomy: control (physiological saline), meloxicam (0.2 mg/kg), dipyrone (25 mg/kg) or dipyrone-meloxicam (25 mg/kg and 0.2 mg/kg, respectively). Glasgow composite measure pain scale (GCMPS) and mechanical nociceptive thresholds (MNT) were assessed before anaesthesia and at 1, 2, 3, 4, 6, 8, 12 and 24 h postoperatively. Rescue analgesia (0.5 mg/kg morphine) was administered intramuscularly if the GCMPS was ≥3. The GCMPS and MNT did not differ among groups. The frequency of rescue analgesia was significantly (P <0.05) lower in the dipyrone group (30%) than in controls (50%), but there were no significant differences from the control group in bitches treated with meloxicam (70%) or dipyrone-meloxicam (40%). There was a significant reduction in the total number of rescue treatments in the dypyrone (n = 5) and dipyrone-meloxicam (n = 5) groups when compared with the control (n = 17) and meloxicam (n = 19) groups. Meloxicam and dipyrone-meloxicam significantly reduced the percentage of animals exhibiting severe pain during MNT measurements (30% and 0%, respectively) compared with the control group (50%). Dipyrone produced superior analgesia (reduced morphine consumption), while meloxicam produced better antihyperalgesia (fewer episodes of severe pain) in contrast to controls. When used in tandem, the beneficial effects were combined.

Analgesic Efficacy of Firocoxib, a Selective Inhibitor of Cyclooxygenase 2, in a Mouse Model of Incisional Pain.

Pain management in laboratory animals is generally accomplished by using opioids and NSAIDs. However, opioid use is hindered by controlled substance requirements and a relatively short duration of action. In this study, we compared the analgesic efficacy of firocoxib (a cyclooxygenase-2-selective NSAID) with that of buprenorphine in the mouse model of plantar incisional pain by objective measurement of mechanical allodynia and thermal hyperalgesia using von Frey and Hargreaves equipment, respectively. Our experimental design included 5 treatment groups: firocoxib at 10 mg/kg IP every 24 h (F10 group); firocoxib at 20 mg/kg IP every 24 h (F20); buprenorphine at 0.2 mg/kg SC every 8 h; intraperitoneal normal saline every 24 h; and sham group (anesthesia, no incision) treated with firocoxib at 20 mg/kg IP every 24 h (sham+F20). All mice underwent nociceptive assays at 24 h before and 4, 24, 48, and 72 h after surgery. Buprenorphine alleviated allodynia at all time points after incision. The F10 treatment alleviated allodynia at 4, 24, and 48 h, whereas F20 alleviated allodynia at 24, 48, and 72 h. None of the treatments alleviated thermal hyperalgesia at 4h. Except for F10 and buprenorphine at 24 h, all treatments alleviated thermal hyperalgesia at 24, 48, and 72 h. No significant differences were noted between the 2 doses of firocoxib and buprenorphine regarding mechanical allodynia and thermal hyperalgesia at all time points. In conclusion, the analgesic efficacy of firocoxib is comparable to that of buprenorphine in this mouse pain model.

Effects of non-steroidal anti-inflammatory drugs on the hyperalgesia to noxious mechanical stimulation induced by the application of a tourniquet to a forelimb of sheep.

A tourniquet was used in conjunction with a mechanical threshold testing device to investigate the suitability of the technique for the investigation of analgesic drugs in sheep. The changes to the mechanical thresholds to noxious stimulation during and after the inflation of a pneumatic tourniquet on a limb were recorded, and the influence of pre-treatment with two non-steroidal anti-inflammatory drugs was studied. Fentanyl, an opioid agonist with known analgesic properties in sheep, was used as a positive control. The tourniquet significantly reduced the mechanical thresholds on the ipsi- but not the contralateral limb. Pretreatment with either flunixin meglumine or carprofen attenuated the development of mechanical hyperalgesia, and fentanyl initially caused a significant anti-nociceptive effect. The time to aversion was not significantly different between the treatments. These results suggest that hyperalgesia induced by a tourniquet may be a useful technique for the investigation of the anti-nociceptive effects of analgesic drugs in sheep.

Use of a new finger-mounted device to compare mechanical nociceptive thresholds in cats given pethidine or no medication after castration.

Mechanical nociceptive thresholds are regularly used to determine the efficacy of analgesic agents both experimentally and clinically in a variety of species. The 'pressure of palpation device' (PPD) was developed for use in cats and is a small battery operated device with a finger-mounted force sensing resistor (FSR, Interlink Electronics, Northumberland. UK). The PPD was used in a study assessing the analgesic efficacy of pethidine after castration in cats. Pethidine was demonstrated to prevent the development of post-operative scrotal hypersensitivity for up to 2 hours after castration, whereas cats given no analgesics showed marked hyperalgesia immediately after surgery. Visual Analogue Scale (VAS) pain scores after castration showed a similar analgesic effect of pethidine. These results suggest that the PPD could become a useful research tool to assess the effectiveness of analgesic agents in the cat.

The influence of lesion type on the duration of hyperalgesia associated with hindlimb lameness in dairy cattle.

The nociceptive thresholds of 42 sound dairy cattle were compared with 53 animals displaying hind-claw lameness. All animals in the study were lameness scored and nociceptive threshold tested. Each animal then received a routine claw trim while the lame cattle also had the cause of lameness determined and treated. Those cattle found to have a unilateral hind-claw lameness (n = 42) were re-evaluated at 28 days after treatment. The lame cattle were found to have a significantly lower nociceptive threshold (P < 0.001) as compared to the sound animals on day 1 and also at retesting on day 28 (P < 0.001). The group which were retested on day 28 were subdivided by lesion type: sole ulcer; white line disease and acute digital tissue infection. Each lesion type caused a decreased nociceptive threshold at day 1. At re-evaluation on day 28 only the thresholds of the acute digital tissue infection group were not significantly different from the sound group but thresholds in sole ulcer and white line disease cows were still depressed.