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Canine neuropathic pain (NeuP) has been poorly investigated. This study aimed to evaluate the pain burden, sensory profile and inflammatory cytokines in dogs with naturally-occurring NeuP. Twenty-nine client-owned dogs with NeuP were included in a prospective, partially masked, randomized crossover clinical trial, and treated with gabapentin/placebo/gabapentin-meloxicam or gabapentin-meloxicam/placebo/gabapentin (each treatment block of 7 days; total 21 days). Pain scores, mechanical (MNT) and electrical (ENT) nociceptive thresholds and descending noxious inhibitory controls (DNIC) were assessed at baseline, days 7, 14, and 21. DNIC was evaluated using ΔMNT (after-before conditioning stimulus). Positive or negative ΔMNT corresponded to inhibitory or facilitatory pain profiles, respectively. Pain scores were recorded using the Client Specific Outcome Measures (CSOM), Canine Brief Pain Inventory (CBPI), and short-form Glasgow Composite Measure Pain Scale (CMPS-SF). Data from baseline were compared to those of sixteen healthy controls. ΔMNT, but not MNT and ENT, was significantly larger in controls (2.3 ± 0.9 N) than in NeuP (-0.2 ± 0.7 N). The percentage of dogs with facilitatory sensory profile was similar at baseline and after placebo (61.5–63%), and between controls and after gabapentin (33.3–34.6%). The CBPI scores were significantly different between gabapentin (CBPI pain and CBPI overall impression ) and/or gabapentin-meloxicam (CBPI pain and interference ) when compared with baseline, but not placebo. The CBPI scores were not significantly different between placebo and baseline. The concentration of cytokines was not different between groups or treatments. Dogs with NeuP have deficient inhibitory pain mechanisms. Pain burden was reduced after gabapentin and/or gabapentin-meloxicam when compared with baseline using CBPI and CMPS-SF scores. However, these scores were not superior than placebo, nor placebo was superior to baseline evaluations. A caregiver placebo effect may have biased the results.

Bupivacaine is commonly used for peripheral nerve block in veterinary medicine. This study described the pharmacokinetics of two doses of bupivacaine following administration by an ultrasound-guided transversus abdominis plane (TAP) block in cats undergoing ovariohysterectomy. Twelve healthy female adult cats were included in a randomized, prospective, blinded clinical trial. Anaesthetic protocol included acepromazine–buprenorphine–propofol–isoflurane–meloxicam. Each cat received 1 mL/kg of bupivacaine 0.2% or 0.25% (BUPI-2 and BUPI-2.5, respectively) via bilateral two-point TAP block before surgery (n = 6/group). Plasma concentrations of bupivacaine were detected using liquid chromatography-mass spectrometry. A one-compartment model and non-compartmental analysis described the pharmacokinetic parameters. Bupivacaine was detected up to 480 min (335 ± 76 in BUPI-2 and 485 ± 198 ng/mL in BUPI-2.5). For BUPI-2 and BUPI-2.5, maximum plasma concentrations were 1166 ± 511 and 1810 ± 536 ng/mL at 33 ± 14 and 47 ± 22 min, clearance was 5.3 ± 1.8 and 4.9 ± 1.5 mL/min/kg, and elimination half-life were 253 ± 55 and 217 ± 52 min, respectively. The two doses of bupivacaine via TAP block produced concentrations below toxic levels in cats. A dose of 2.5 mg/kg bupivacaine was safe to be administered using this block in healthy cats.

This study aimed to evaluate the effects of sedation and anesthesia on Feline Grimace Scale© (FGS) scores. Twelve healthy cats were included in a prospective, blinded and randomized, cross-over study with a 14 day wash-out. Saline or dexmedetomidine-butorphanol (Dex-But) was administered intramuscularly before an anesthetic induction with propofol and maintenance with isoflurane. Saline or atipamezole (Dex-But) was administered at the end of the general anesthesia. Video-filming/image capturing was performed before and up to 24 h post-anesthesia. A total of 125 images were evaluated by four raters blinded to the treatment groups using the FGS (ear position/orbital tightening/muzzle tension/whiskers change/head position; action units (AU); scores 0–2 for each AU). The effects of the sedation/anesthesia were analyzed (p < 0.05). The total FGS and each AU scores were significantly higher with Dex-But than with saline 20 min post-sedation. In the saline group, the total FGS, orbital tightening, and whiskers and head position scores were significantly higher than baseline at 0.5 h post-anesthesia. In the Dex-But group, the total FGS and each AU scores were significantly higher after sedation, whereas the orbital tightening scores were significantly higher at 0.5 h post-anesthesia when compared with the baseline. None of the other comparisons between or within the groups was significantly different. The sedation with dexmedetomidine-butorphanol and anesthesia with propofol-isoflurane changed the FGS scores on a short-term basis; consequently, they may bias acute pain assessment.

This study aimed to evaluate the inter-rater reliability of the Feline Grimace Scale (FGS) in cats undergoing dental extractions and the effects of the caregiver's presence on the FGS scores. Twenty-four cats (6 ± 3.3 years old; 4.9 ± 1.7 kg) undergoing oral treatment were included in a prospective, blinded, randomized, clinical study. They underwent treatment under general anesthesia (acepromazine-hydromorphone-propofol-isoflurane-meloxicam-local anesthetic blocks) at day 1 and were discharged at day 6. Images of cat faces were captured from video recordings with or without the caregiver's presence at 6 h postoperatively (day 1), day 6, and before and after rescue analgesia. Images were randomized and independently evaluated by four raters using the FGS [five action units (AU): ear position, orbital tightening, muzzle tension, whiskers change, and head position; score 0–2 for each]. Inter-rater reliability and the effects of the caregiver's presence were analyzed with intraclass correlation coefficient [single measures (95% confidence interval)] and the Wilcoxon signed-rank test, respectively ( p < 0.05). A total of 91 images were scored. Total FGS scores showed good inter-rater reliability [0.84 (0.77–0.89)]. Reliability for each AU was: ears [0.68 (0.55–0.78)], orbital tightening [0.76 (0.65–0.84)], muzzle [0.56 (0.43–0.69)], whiskers [0.64 (0.50–0.76)], and head position [0.74 (0.63–0.82)]. The FGS scores were not different with [0.075 (0–0.325)] or without [0.088 (0–0.525)] the caregivers' presence ( p = 0.12). The FGS is a reliable tool for pain assessment in cats undergoing dental extractions. The caregiver's presence did not affect FGS scores.

Pain is the leading cause of animal suffering, hence the importance of validated tools to ensure its appropriate evaluation and treatment. We aimed to test the psychometric properties of the short form of the Unesp-Botucatu Feline Pain Scale (UFEPS-SF) in eight languages. The original scale was condensed from ten to four items. The content validation was performed by five specialists in veterinary anesthesia and analgesia. The English version of the scale was translated and back-translated into Chinese, French, German, Italian, Japanese, Portuguese and Spanish by fluent English and native speaker translators. Videos of the perioperative period of 30 cats submitted to ovariohysterectomy (preoperative, after surgery, after rescue analgesia and 24 h after surgery) were randomly evaluated twice (one-month interval) by one evaluator for each language unaware of the pain condition. After watching each video, the evaluators scored the unidimensional, UFEPS-SF and Glasgow composite multidimensional feline pain scales. Statistical analyses were carried out using R software for intra and interobserver reliability, principal component analysis, criteria concurrent and predictive validities, construct validity, item-total correlation, internal consistency, specificity, sensitivity, the definition of the intervention score for rescue analgesia and diagnostic uncertainty zone, according to the receiver operating characteristic (ROC) curve. UFEPS-SF intra- and inter-observer reliability were ≥0.92 and 0.84, respectively, for all observers. According to the principal component analysis, UFEPS-SF is a unidimensional scale. Concurrent criterion validity was confirmed by the high correlation between UFEPS-SF and all other scales (≥0.9). The total score and all items of UFEPS-SF increased after surgery (pain), decreased to baseline after analgesia and were intermediate at 24 h after surgery (moderate pain), confirming responsiveness and construct validity. Item total correlation of each item (0.68-0.83) confirmed that the items contributed homogeneously to the total score. Internal consistency was excellent (≥0.9) for all items. Both specificity (baseline) and sensitivity (after surgery) based on the Youden index was 99% (97-100%). The suggestive cut-off score for the administration of analgesia according to the ROC curve was ≥4 out of 12. The diagnostic uncertainty zone ranged from 3 to 4. The area under the curve of 0.99 indicated excellent discriminatory capacity of UFEPS-SF. The UFEPS-SF and its items, assessed by experienced evaluators, demonstrated very good repeatability and reproducibility, content, criterion and construct validities, item-total correlation, internal consistency, excellent sensitivity and specificity and a cut-off point indicating the need for rescue analgesia in Chinese, French, English, German, Italian, Japanese, Portuguese and Spanish.

This study aimed to compare the analgesic effects of an injectable protocol using multimodal analgesia with or without opioids in cats undergoing ovariohysterectomy (OVH). Thirty-two healthy cats were enrolled in a prospective, blinded, randomized trial after the caregiver's written consent. Cats received a combination of ketamine (4 mg/kg), midazolam (0.25 mg/kg) and dexmedetomidine (40 μg/kg), and either buprenorphine (20 μg/kg) or saline (same volume as buprenorphine) intramuscularly [opioid-sparing (OSA) and opioid-free anesthesia (OFA) groups, respectively]. Intraperitoneal bupivacaine 0.25% (2 mg/kg) and meloxicam (0.2 mg/kg subcutaneously) were administered before OVH. Atipamezole (400 μg/kg intramuscularly) was administered at the end of surgery. Pain and sedation were evaluated using the Feline Grimace Scale (FGS) and a dynamic interactive visual analog scale, respectively. Intravenous buprenorphine was administered as rescue analgesia if FGS scores ≥ 0.39/1. Statistical analysis included repeated measures linear mixed models, Fisher's exact test and Bonferroni adjustments when appropriate ( p < 0.05). Twenty-seven cats were included. The prevalence of rescue analgesia was lower in OSA ( n = 0/13) than in OFA ( n = 5/14) ( p = 0.04). The FGS scores (least square means and 95% CI) were higher in OFA at 1 [2.0 (1.3–2.7)] and 2 h [2.2 (1.5–2.9)] than baseline [0.7 (0.0–1.4)], but not in OSA. Sedation scores were not significantly different between groups. Opioid-free injectable anesthesia was appropriate for some cats using a multimodal approach. However, a single dose of intramuscular buprenorphine eliminated the need for rescue analgesia and assured adequate pain management after OVH in cats.

Quantitative sensory testing has been used to assess the somatosensory system. This study aimed to evaluate the feasibility and reliability of electrical (ENT), mechanical (MNT) and thermal (TNT) nociceptive testing and the effect of a conditioning stimulus on MNT. Sixteen healthy client-owned dogs were included in this study. Stimulation was applied bilaterally to the dorsal and plantar aspect of the metacarpus and metatarsus respectively, using transcutaneous electrical stimulator, algometry and a cold nociceptive device in a randomized order until a behavior response was observed or a cut-off reached. Tests were performed twice (60 seconds apart) by two observers. Retesting was performed 5 hours later. The diffuse noxious inhibitory control was tested by comparing MNT pre- and post-conditioning stimuli. Sham-testing was performed for ENT and TNT. Statistical analysis included linear model and intra-class correlation coefficient ( <0.05). Feasibility was 99% (ENT), 93.5% (MNT) and 93.6% (TNT). Data for TNT were not analyzed due to inconsistent results. Mean ± SD were 48±22.6 mA (ENT) and 11.9±3.5 N (MNT). MNT was higher for thoracic than for pelvic limbs ( =0.002). Conditioning stimulus increased MNT ( =0.049). Inter-observer reliability was 91.4% (ENT) and 60.9% (MNT). False-positive responses were 15% (ENT) and 35.7% (TNT). ENT was feasible, repeatable and superior to MNT and TNT. The assessment of the diffuse noxious inhibitory control with a conditioning stimulus showed promising results in dogs. These tools could be used in naturally-occurring disease to provide insight on their underlying mechanisms and therapeutics.