Expression of Cannabinoid Receptors in the Trigeminal Ganglion of the Horse.

Cannabinoid receptors are expressed in human and animal trigeminal sensory neurons; however, the expression in the equine trigeminal ganglion is unknown. Ten trigeminal ganglia from five horses were collected post-mortem from an abattoir. The expression of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), and the cannabinoid-related receptors like transient receptor potential vanilloid type 1 (TRPV1), peroxisome proliferator-activated receptor gamma (PPARÉ£), and G protein-related receptor 55 (GPR55) in the trigeminal ganglia (TG) of the horse were studied, using immunofluorescence on cryosections and formalin-fixed paraffin-embedded (FFPE) sections. Neurons and glial cells were identified using fluorescent Nissl staining NeuroTrace® and an antibody directed against the glial marker glial fibrillary acidic protein (GFAP), respectively. Macrophages were identified by means of an antibody directed against the macrophages/microglia marker ionized calcium-binding adapter molecule 1 (IBA1). The protein expression of CB1R, CB2R, TRPV1, and PPARÉ£ was found in the majority of TG neurons in both cryosections and FFPE sections. The expression of GPR55 immunoreactivity was mainly detectable in FFPE sections, with expression in the majority of sensory neurons. Some receptors were also observed in glial cells (CB2R, TRPV1, PPARγ, and GPR55) and inflammatory cells (PPARγ and GPR55). These results support further investigation of such receptors in disorders of equine trigeminal neuronal excitability.

Is Electrical Nerve Stimulation the Answer for Management of Equine Headshaking?

Horses with trigeminal mediated headshaking (TMHS) have a decreased activation threshold of the trigeminal nerve and clinical signs are suspected to be a manifestation of trigeminal neuralgia. Electrical nerve stimulation (ENS) is used for management of neuralgia in humans and appears to work via gate control theory. Use of an equine specific percutaneous ENS program in over 130 TMHS horses has resulted in approximately 50% success return to previous work. Electroacupuncture may also be useful in the management TMHS. Optimization of ENS procedures for TMHS is likely to require a greater understanding of the etiopathogenesis of the aberrant neurophysiology.

Use of a poll-mounted accelerometer for quantification and characterisation of equine trigeminal-mediated headshaking.

BACKGROUND: Equine trigeminal-mediated (TGM) headshaking (HS) is a neuropathic facial pain syndrome characterised by varying intensity and frequencies of head movements and signs of nasal irritation. An accurate method for quantification and/or characterisation of HS severity is lacking. OBJECTIVES: To develop and validate an objective measure of TGMHS. STUDY DESIGN: Prospective case control study. METHODS: Horses presenting for investigation of HS were recruited alongside those presenting for forelimb lameness (LAME) and pre-purchase examination as well as healthy controls (CONTROL). Head movement data were collected for 5 min whilst trotting on the lunge using a tri-axial accelerometer, with a range of ±16 g and sampling rate of 800 Hz, attached to the bridle headpiece. Recordings were exported for processing. Peak detection was performed using minimum and maximum thresholds of -1 g and +1 g (corrected for gravity) and a minimum peak width of 10 samples. RESULTS: Fifty-six horses were included in the study; 18 TGMHS, 10 non-TGMHS, 12 LAME and 16 CONTROL. Characteristics and frequency of vertical (Z axis) head movements of TGMHS horses differed significantly from other horses. TGMHS horses had peaks with greater mean and maximum positive g-force (P < 0.005) and lower mean and minimum negative g-force (P < 0.001), greater frequency of peaks/min (P < 0.001) and over 12 times greater percentage of peaks >+2 g compared with other horses (P < 0.001). Receiver operator curve characteristics of percentage of peaks >+2 g (CI 0.72-0.95), percentage of peaks <-2 g (CI 0.66-0.92) and percentage of peaks <-2 g and >+2 g (CI 0.72-0.96) showed excellent discrimination of TGMHS horses from LAME, CONTROL and non-TGMHS horses. MAIN LIMITATIONS: Referral population of horses, small sample size and control horses were not evaluated for orthopaedic disease. CONCLUSIONS: Accelerometer data from trotting exercise on the lunge provides an objective measure of HS and can differentiate between TGMHS, non-TGMHS, normal head movements and those associated with forelimb lameness. Accelerometer use may aid HS diagnosis and monitoring of management strategies.

HISTORIAL: La sacudida de cabeza (HS) en equinos mediada por el nervio trigémino (TGM), es un síndrome de dolor facial neuropático caracterizado por movimientos de cabeza de intensidad y frecuencia variables y por síntomas de irritación nasal. No existe un método preciso para cuantificar y/o caracterizar la gravedad de HS. OBJETIVOS: Desarrollar y validar una medida objetiva de TGMHS. DISEÑO DEL ESTUDIO: Estudio prospectivo de casos y controles. MÉTODOS: Caballos presentados para la investigación de HS fueron reclutados junto a aquellos presentados para cojera de mano (LAME) y examen de pre­compra como controles saludables (CONTROL). Datos de los movimiento de la cabeza fueron recolectados durante cinco minutos mientras trotaban a la cuerda usando un acelerómetro tri­axial, con un rango de ±16 g y frecuencia de muestreo de 800 Hz, ajustado a la testera de la cabezada. Las grabaciones se exportaron para ser procesadas. Detección de picos fue realizada usando umbrales mínimos y máximos de −1g y + 1g (corregidos para gravedad) y un muestreo mínimo de 10 picos de ancho. RESULTADOS: Cincuenta y seis caballos fueron incluidos en el estudio; 18 TGMHS, 10 no­TGMHS, 12 LAME y 16 CONTROL. Las características y la frecuencia de los movimientos de cabeza verticales (eje Z) de caballos TGMHS, difirieron significativamente de otros caballos. Los caballos TGMHS presentaron picos con una fuerza­g positiva con mayor promedio y máxima (P < 0.005) y una fuerza­g negativa con menor promedio y mínima (P < 0.001), con mayor frecuencia de picos/min (P < 0.001), y un porcentaje mas de doce veces mayor de picos >+2 g en comparación a los otros caballos (P < 0.001). Las características de las curvas del operador del receptor de los picos promedio >+2 g (CI 0.72­0.95), del porcentaje de picos <−2 g (CI 0.66­0.92), y del porcentaje de picos <−2 g y > +2 g (CI 0.72­0.96) mostraron una excelente discriminación de caballos TGMHS con respecto a caballos LAME, CONTROL y no­TGMHS. LIMITACIONES PRINCIPALES: Población de caballos derivados, numero de muestra pequeño, y los caballos control no fueron evaluados por enfermedades ortopédicas. CONCLUSIONES: Los datos de acelerómetros por trote a la cuerda, dan una medida objetiva de HS y permiten diferenciar entre TGMHS, no­TGMHS, movimientos normales de cabeza y aquellos asociados a cojera de mano. El uso de acelerómetros puede ayudar en el diagnostico de HS y monitorear las estrategias de manejo.

History, Rest and Exercise Score (HRE-S) for assessment of disease severity in horses with trigeminal-mediated headshaking.

BACKGROUND: In horses with trigeminal-mediated headshaking (TMHS), clinical signs are likely to be expression of neuropathic facial pain. Currently, subjective assessment of disease severity is used as measure of compromise of animal's welfare. OBJECTIVES: To develop and validate a precise scoring system for TMHS: History, Rest and Exercise Score (HRE-S). The HRE-S consists of three subscores: history score (H-S), resting score (R-S) and exercise score (E-S). STUDY DESIGN: Retrospective observational study. METHODS: Seven masked observers with different experience used HRE-S to score 40 video recordings taken during rest and lungeing including five duplicates. Video recordings were taken from nine horses with TMHS and three controls. Inter- and intraobserver reliability and practicability of HRE-S were assessed. For every video recording severity of clinical signs was graded by every observer using an intuitive global-type-scale and interobserver reliability was calculated. Convergent validity was evaluated comparing HRE-S to groups created by an existing score (grade 0-3). Discriminant validity was analysed comparing HRE-S to groups created by intuitive global-type-scale. RESULTS: Reliability for HRE-S was excellent, irrespective of observers experience: Spearman's Rho = 0.946, p < 0.001 (intraobserver reliability) and intraclass correlation coefficient = 0.98, p < 0.001 (interobserver reliability). Interobserver reliability for intuitive global-type-scale was fair to substantial: Fleiss' κappa = 0.48 (R-S) -0.63 (E-S). Groups created by intuitive global-type-scale had significantly different R-S and E-S (p < 0.05), demonstrating discriminant validity. Convergent validity was proven as horses with grade 3/3 had significantly higher average E-S and total scores compared with an existing score than those with grade 0/3 or 1/3 (p < 0.001). MAIN LIMITATIONS: Retrospective nature, video recordings, sample size. CONCLUSIONS: HRE-S is a valid and reliable score evaluating disease severity in TMHS, independent of observers' experience.

Mental wellbeing and psychosocial working conditions of autistic veterinary surgeons in the UK.

BACKGROUND: Certain autistic characteristics (such as hyper-focus and attention to detail) are valued by veterinary surgeons and autistic adults may disproportionately self-select into the profession. Links between mental wellbeing and retention in the veterinary profession highlight an imperative to profile autistic veterinary surgeons' mental wellbeing and identify protective factors. The psychosocial work environment may represent one such protective factor. We aimed to assess autistic veterinary surgeons' mental wellbeing, the extent to which their psychosocial working conditions achieved UK government management standards and links between these. METHODS: Eighty-five autistic veterinary surgeons completed the Warwick-Edinburgh Mental Wellbeing Scale and the Health and Safety Executive's Management Standards Indicator Tool. Descriptive comparisons were drawn with normative data; correlation and linear regression analyses examined relations between mental wellbeing and psychosocial working conditions. RESULTS: Mental wellbeing and psychosocial work environment quality were markedly below veterinary surgeon and general workforce norms. Psychosocial working conditions accounted for 44% of the unique variance in mental wellbeing, with 'control' and 'role' making a significant contribution. LIMITATION: This exploratory study involved a small self-selecting sample, raising the possibility of response bias. CONCLUSION: Work design centred on the enhancement of control and role clarity would likely support mental wellbeing in this population.

Idiopathic headshaking: is it still idiopathic?

The clinical syndrome of equine idiopathic headshaking (HSK) was first described in the veterinary literature over 100 years ago, and the disorder continues to be a cause of substantial distress for the horse, frustration for the owner and therapeutic challenge for the veterinarian. This review presents a summary of the current knowledge of clinical signs, signalment, aetiopathogenesis, anatomy, diagnosis and treatment of idiopathic HSK. Recent advances in understanding the pathogenesis of the disease will be discussed with reference to human trigeminal neuralgia, along with the implications this may have for potential therapies.

Expression of annexin-1 in equine leucocytes and the effects of the N-terminal annexin-1 peptide, Ac2-26, on equine neutrophil superoxide production.

N-terminal peptides derived from the anti-inflammatory peptide, annexin-1, inhibit neutrophil function but can also induce pro-inflammatory effects. Although equine annexin-1 has been sequenced, its cellular expression and properties have not been reported. This study has examined whether annexin-1 is present in equine leucocytes and how the N-terminal peptide, Ac2-26, affects equine neutrophil superoxide production. Annexin-1 expression in equine neutrophils and mononuclear cells and the ability of Ac2-26 to activate neutrophil p42/44 MAPK were determined by immunoblotting. Equine neutrophil superoxide production was measured by the reduction of cytochrome (cyt) C following stimulation with Ac2-26 and the formyl peptide receptor (FPR) agonists, FMLP, WKYMVm and WKYMVM. Responses were examined in the presence of the pan-FPR antagonist, BOC-2, and the role of p42/44 MAPK in agonist-induced effects was determined using PD98059. The effect of Ac2-26 on superoxide production in response to serum-treated zymosan (STZ) was also investigated, and the roles of FPR and p42/44 MAPK ascertained. Annexin-1 was detected in both equine neutrophils and mononuclear cells using a polyclonal rabbit anti-human annexin-1 antibody. Ac2-26 (5x10(-5)M) induced superoxide production in cytochalasin B-primed (48+/-8 versus 21+/-9 (unstimulated cells) nmol cyt C/10(6) neutrophils) and un-primed cells (37+/-10 versus 11+/-5 nmol cyt C/10(6) neutrophils). FMLP and WKYMVm, but not WKYMVM, also caused superoxide production in primed neutrophils, suggesting the response was mediated by FPR receptor binding. This was supported by the marked inhibitory effect of BOC-2 on the responses to Ac2-26 and FMLP although, interestingly, the effects of WKYMVm were not significantly reduced (50+/-5 (WKYMVm) versus 45+/-5 (WKYMVm+BOC-2) nmol reduced cyt C/10(6) neutrophils). Inhibition of p42/44 MAPK activation with PD98059 significantly attenuated superoxide production in response to Ac2-26, FMLP and WKYMVm and Western blotting showed that Ac2-26 induced p42/44 MAPK activation. At a concentration which did not cause superoxide production, Ac2-26 (10(-5)M) significantly reduced the response to STZ (84+/-17% inhibition). This inhibitory effect was attenuated by both BOC-2 and PD98059. These results suggest that if activation of equine leucocytes in vivo leads to the release and subsequent cleavage of annexin-1, the N-terminal peptides formed could bind to neutrophil FPR and decrease free radical production in response to particulate stimuli. This could help to reduce local tissue damage but, as Ac2-26 can also stimulate superoxide production at higher concentrations in an FPR-dependent manner, the amount of free radical production may depend on the concentration of peptide present.