Pain Flashcards
Pain severity scores for common equine disorders as provided by horse owners and equine veterinarians
• Pain severity ratings varied significantly between horse owners and veterinarians.
• Owners tended to rate pain severity higher than veterinarians in conditions such as castration, laceration, and gas colic.
• Veterinarians rated pain severity higher in subsolar abscesses, dental float procedures, and fractured pasterns.
Confidence in Pain Recognition:
• 91% of horse owners expressed confidence in their veterinarians’ ability to recognize pain.
• Only 14% of veterinarians believed horse owners could accurately assess pain in their horses.
• Veterinarians reported higher confidence in their own pain assessment skills (86%) than horse owners’ assessments.
Factors Affecting Pain Ratings:
• Horse owners with fewer than 10 horses and no college education were more likely to give high pain ratings.
• Veterinarians employed in mixed-animal practices and without board certification were more likely to rate pain higher.
• Male veterinarians were more likely to assign low pain ratings compared to female veterinarians.
Demographic Insights
Horse Owners:
• Owners who managed fewer horses or lacked formal education were more sensitive to signs of pain, possibly due to less frequent exposure to painful conditions.
• Those with more horses might normalize subtle pain behaviors, reducing their sensitivity.
Veterinarians:
• Mixed-animal practitioners might encounter fewer equine cases, leading to less confidence and higher pain assessments.
• Gender differences were significant, with female veterinarians consistently rating pain higher for procedures, while differences in naturally occurring conditions were minimal.
Pain Severity Comparisons for Common Scenarios:
• Castration: Median score: Owners 6, Veterinarians 5. Indicates a slight underestimation by veterinarians compared to owners.
• Subsolar Abscess: Median score: Owners 8, Veterinarians 8. Similar scores, but veterinarians provided slightly higher maximum values.
• Gas Colic: Median score: Owners 7, Veterinarians 7. Agreement in ratings, indicating shared recognition of colic’s severity.
Inflammatory mediators are potential biomarkers for extracorporeal shockwave therapy in horses
A single dose of extracorporeal shockwave therapy (ESWT) significantly altered plasma concentrations of:
• Upregulated: TNF-α, IL-1RA, TLR2.
• Downregulated: IL-1β, IL-6.
• Changes were greatest at 24-72 hours
• TNF-α, IL-1RA, and TLR2 may serve as plasma biomarkers to detect ESWT application in horses, particularly in regulatory contexts (e.g., pre-competition screening).
Application of an equine composite pain scale and its association with plasma adrenocorticotropic hormone concentrations and serum cortisol concentrations in horses with colic
• The CPS was adapted to include physiological parameters (heart rate and respiratory rate) and extended observation times to 10 minutes for increased accuracy.
• The scale demonstrated excellent inter-observer reliability (weighted kappa 0.863), affirming its consistency among trained observers.
Pain and Cortisol Association:
• A significant positive association was found between CPS scores and serum cortisol concentrations:
-Most painful time point: Rho = 0.581, P < 0.001.
-All time points: Rho = 0.441, P < 0.001.
• For every unit increase in CPS, serum cortisol increased by an average of 1.423 pg/mL at the most painful time point.
Lack of Association with ACTH:
• No significant association was found between CPS scores and plasma ACTH concentrations at the most painful time point (P = 0.234).
• A weak association between cortisol and ACTH was observed when considering all time points (P = 0.034), indicating potential decoupling of the HPA axis in severe stress or disease.
CPS Metrics:
• CPS items like “pain face” had the lowest inter-observer reliability, possibly due to subjectivity.
• Other items, such as posture, activity levels, and head position, contributed robustly to the scale’s overall reliability.
Development and preliminary validation of a pain scale for ophthalmic pain in horses: The Equine Ophthalmic Pain Scale (EOPS)
• The study developed and validated the Equine Ophthalmic Pain Scale (EOPS) to assess ocular pain in horses using behavioral, physiological, and ocular expression indicators.
• The total score (TS) could range from 0 (no pain) to 31 (maximum pain).
• See (81.3%) Sp (100%) for detecting ocular pain at an optimal cut-off of TS ≥ 7.
• The area under the curve (AUC = 0.918) confirmed the scale’s high accuracy in distinguishing between healthy and pathological horses.
• TS significantly decreased in horses with ophthalmic disease after one week of medical or surgical treatment (P = 0.017)
• Inter-Observer Reliability: Most items in the behavioral and ocular expression categories demonstrated excellent reliability (ICC ≥ 0.75).
-Items like “position inside the box” and “overall behavior” showed moderate reliability, indicating the need for refinement.
• Internal Consistency: Cronbach’s alpha was 0.76, indicating good internal consistency.
• Removing items like “heart rate,” “respiratory rate,” and “rectal temperature” could improve consistency.
Construct and Criterion Validity:
• Horses with ocular pain had significantly higher TS compared to healthy horses (P < 0.001).
• Logistic regression indicated a two-fold increase in the likelihood of ocular pathology with each additional TS point (OR = 2.589, P < 0.001).
Key pain-related indicators included:
• Behavioral: Overall behavior, position in the box, head position, response to door opening.
• Ocular: Blepharospasm, lacrimation, response to eyelid opening.
• Physiological: Heart rate, respiratory rate, rectal temperature, mucous membrane color.
• Ocular indicators like blepharospasm and lacrimation were highly reliable and provided specific insights into pain levels.
A survey of non-steroidal anti-inflammatory drug use in the post-operative period following equine colic surgery
• NSAIDs are integral in managing post-operative pain and inflammation in colic patients.
• Flunixin meglumine and phenylbutazone were the most commonly used NSAIDs, reflecting their widespread availability.
• Less commonly used NSAIDs included meloxicam, firocoxib, ketoprofen, carprofen, vedaprofen, and suxibuzone.
Dosing Patterns:
• Flunixin was frequently administered at 1.1 mg/kg every 12 hours, despite the licensed dose being every 24 hours.
• Phenylbutazone was commonly given at 2.2 mg/kg every 12 hours for adult horses.
• Newer NSAIDs like firocoxib and meloxicam were used at licensed doses (e.g., firocoxib at 0.1 mg/kg every 24 hours, meloxicam at 0.6 mg/kg every 24 hours).
The top factors for discontinuing NSAID administration were:
• Absence of active colic signs (83%).
• Pain score evaluation (81%).
• Absence of fever in the preceding 24 hours (78%).
Less important factors included:
• Licensing criteria for drug duration.
• Presence of incisional swelling or drainage.
Duration of NSAID Use:
• NSAID administration typically ceased within 5–7 days post-operatively if no complications occurred.
• Prolonged use (up to 10 days or more) was associated with post-operative complications, such as SIRS, ileus, or incisional infections.
The cannabinoid receptors system in horses: Tissue distribution and cellular identification in skin
• Both cannabinoid receptor types, CBR1 and CBR2, were identified in equine skin.
• Expression was detected in epidermal keratinocytes and dermal fibroblast-like cells.
• CBR2 expression was significantly higher than CBR1 in epidermal and dermal compartments.
Localization and Distribution:
• CBR1: Detected primarily in the cytoplasm of keratinocytes, with limited expression in hair follicles and sebaceous glands.
• CBR2: Strongly expressed in hair follicles, sebaceous glands, and sweat glands. It was predominant in the inner root sheath and dermal papilla of hair follicles.
• Peripheral nerve fibers in the dermis, marked with PGP 9.5, co-localized with both CBRs, linking the cannabinoid system with neuroimmune functions.
• Higher relative mRNA expression of both receptors was observed in the brain compared to skin samples.
• CBR2 expression in fibroblasts and keratinocytes was more prominent than CBR1, suggesting its critical role in skin homeostasis.
Neuroimmune Regulation:
• The presence of CBRs in dermal nerve fibers and immune cells highlights the role of the endocannabinoid system (ECS) in maintaining skin homeostasis.
• Co-localization with PGP 9.5 suggests interaction between ECS and peripheral sensory neurons, influencing inflammatory and sensory pathways.
• CBR2’s higher expression in sebaceous glands and hair follicles aligns with its anti-inflammatory and regenerative functions.
• Targeting CBRs could help manage equine skin conditions like dermatitis or wounds, reducing inflammation and promoting healing.
Pharmacokinetics and oral bioavailability of cannabidiol in horses
• Cannabidiol (CBD) displayed a tri-compartmental distribution profile, indicative of widespread tissue penetration.
• The volume of distribution (Vss) was large (36 L/kg), suggesting significant sequestration in tissues like fat, central nervous system, and joints.
• Clearance (Cl) was high at 1.46 L/h/kg, pointing to efficient hepatic elimination.
• The oral bioavailability of CBD was low (~14%), consistent across both sesame oil and micellar formulations.
• Micellar formulations provided faster absorption and higher peak plasma concentrations (Cmax) compared to oil formulations, but bioavailability remained similar.
Absorption and Bioavailability:
• Low oral bioavailability is attributed to CBD’s high lipophilicity, limited intestinal absorption, and extensive hepatic first-pass metabolism.
Half-life and Steady-State:
• The terminal half-life (t1/2) was approximately 24-34 hours, longer than prior studies, reflecting slow drug release from peripheral compartments.
• Simulations indicated steady-state concentrations were reached after 6-7 days with twice-daily oral administration.
Therapeutic Applications:
• Both micellar and oil-based formulations can be used for oral CBD administration, with the choice depending on desired pharmacokinetic profiles:
-Micellar formulations: Faster peak levels, suitable for acute conditions.
-Oil formulations: Sustained levels, possibly better for chronic conditions.
Mechanistic Insights:
• First-Pass Effect: Extensive first-pass metabolism by the liver contributes significantly to CBD’s low systemic availability after oral administration. The presence of major metabolites (e.g., 7-COOH CBD) in other studies supports this finding.
• Lipophilic Drug Challenges: The high lipophilicity (log P ~6.3) and low water solubility of CBD necessitate lipid-based or micellar delivery systems for improved absorption.
The effect of regional hypothermia on mechanical nociceptive thresholds in the equine distal forelimb
• Hypothermia increased the mechanical nociceptive threshold (MNT) in equine distal forelimbs when skin surface temperatures were cooled to below 7°C.
• Each 1°C decrease below 7°C resulted in a 1.44 N increase in the force required to elicit a pain response (P = 0.036).
• To achieve a skin surface temperature of 7°C, the water temperature required was below 2°C.
• No consistent association was found between MNT and temperatures above 7°C.
Acquisition and use of analgesic drugs by horse owners in the United States
• 96% of horse owners had at least one analgesic drug available for immediate use.
• The most common drugs: Oral phenylbutazone (87%). Injectable flunixin meglumine (60%).
• 18% of owners had five or more types of analgesic drugs available.
• 71.9% administered 1–4 types of drugs in the last two years, while 24.9% used 5–9 types.
• Only 60.5% felt confident administering intravenous drugs, reflecting awareness of associated risks.
Sources of Drug Acquisition:
• 27% of owners occasionally obtained drugs from non-VCPR (Veterinarian-Client-Patient Relationship) compliant sources, such as:
-Feed stores (19.3%).
-Online pharmacies without prescriptions (12.6%).
• Most compliant sources included veterinarians who had recently examined the horse (98.7%).
Factors Influencing Drug Possession
• Characteristics of Owners with ≥5 Drug Types:
-Managed >20 horses in their lifetime (OR = 3.1).
-Medical insurance for some horses (OR = 4.2).
-Veterinary or medical training (OR = 2.2).
-Primary care veterinarian travel time ≤30 minutes (OR = 0.5).
• Non-VCPR Compliant Drug Acquisition:
-Likely among younger owners (<40 years, OR = 2.0).
-More common in males (OR = 5.6).
-Predominantly in the Southern and Western US regions (OR = 2.4).
Extracorporeal shockwave therapy raises mechanical nociceptive threshold in horses with thoracolumbar pain
• NB not controlled, not blinded
• Three extracorporeal shockwave therapy (ESWT) treatments increased mechanical nociceptive threshold (MNT) across thoracolumbar spinal sites in 83% of horses.
• The average MNT increase:
-Thoracic region (T12–T18): 64%.
-Lumbar region (L3–L5): 29%.
• A bimodal pain relief response was observed:
-Initial analgesia within 7 days post-treatment.
- Recurrence of pain followed by a gradual reduction over 3–4 weeks, consistent with tissue healing processes.
• Radiographic pathology severity (spinous process impingement, articular facet remodeling) did not correlate with MNT response.
• Multifidus muscle cross-sectional area (CSA) remained unchanged during the study, indicating ESWT alone may not enhance muscle regeneration.
• Moderate individual variability in response
Mechanisms of Action
• Initial analgesia likely results from ESWT’s effects on nociceptive signaling, including altered nerve conduction and reduced sensitivity.
• Potential histological changes include disruption of nerve myelin sheaths and reduced nerve function.
• Secondary analgesia is attributed to angiogenesis, tissue matrix remodeling, and reduced inflammation.
Acupuncture has potential in managing axial stiffness in steeplechase racehorses
Efficacy of Acupuncture:
• Horses receiving acupuncture demonstrated significant improvements in axial mobility and stiffness:
• All horses in the treatment group (6/6) showed improvement compared to only 1/6 in the control group by Day 7 and Day 14 (P = .01).
• Subjective dorsal flexibility scores were significantly higher in the acupuncture group (median: 0.50) compared to the control group (-0.25; P = .04).
Secondary Observations:
• Visual evaluation by experts indicated better back mobility during trotting and free jumping in treated horses.
• No significant differences in thoracolumbar mobility were detected using inertial measurement units (IMUs), possibly due to variability in the assessment method.
Treatment using cannabidiol in a horse with mechanical allodynia
A 4-year-old Quarter Horse mare presented with a 5-week history of mechanical allodynia, characterized by marked hypersensitivity to light touch in the withers and shoulder region.
Clinical signs included twitching, kicking, and violent reactions to touch, even in the absence of visible stimuli.
• Diagnostic imaging (radiographs of the cervical spine and withers) and laboratory evaluations (CBC, chemistry profile, reproductive hormone panel) were unremarkable.
• Differential diagnoses included: Syringohydromyelia. Neuropathic pain or idiopathic cutaneous hyperesthesia. Behavioral causes.
Treatment Course:
• Initial therapies included dexamethasone, gabapentin, prednisolone, magnesium, vitamin E supplementation, and aquapuncture, all of which failed to improve clinical signs.
• Introduction of pure crystalline cannabidiol (CBD) at a dose of 250 mg twice daily led to marked improvement in clinical signs within 36 hours:
-The mare tolerated light and firm touch and was able to be lunged with a saddle without adverse behaviors.
Cannabidiol (CBD) Mechanism and Effectiveness
Mechanism of Action:
• CBD acts on CB1 and CB2 cannabinoid receptors:
-CB1 receptors (central nervous system): Modulate neurotransmitter release, reducing nociceptive signaling and anxiety.
-CB2 receptors (periphery): Mediate immune responses, reducing inflammation and pain.
• CBD also interacts with opioid receptors, enhancing analgesic effects.
