Gabapentin for the treatment of neuropathic pain in a pregnant horse

CASE DESCRIPTION: A 24-year-old 732-kg (1,610-lb) pregnant Belgian draft horse mare developed neuropathy and signs of intractable pain following colic surgery. CLINICAL FINDINGS: Following recovery from colic surgery to treat compression of the small and large intestines because of a large fetus, the mare was noticed to have signs of femoral neuropathy involving the left hind limb. Within 36 hours after recovery, the mare developed signs of severe pain that were unresponsive to conventional treatment. No gastrointestinal tract or muscular abnormalities were found, and the discomfort was attributed to neuropathic pain. TREATMENT AND OUTCOME: The mare was treated with gabapentin (2.5 mg/kg [1.1 mg/lb], PO, q 12 h). Shortly after this treatment was initiated, the mare appeared comfortable and no longer had signs of pain. Treatment was continued for 6 days, during which the dosage was progressively decreased, and the mare was discharged. The mare subsequently delivered a healthy foal. CLINICAL RELEVANCE: Gabapentin appeared to be a safe, effective, and economical treatment for neuropathic pain in this horse.     

Glycerol,Methyl‐Formamide and Dimethyl‐Formamide in Canine Semen Cryopreservation

The aim of the present work was to compare the efficiency of methyl‐formamide (MF), dimethyl‐formamide (DF) and glycerol (GL) as cryoprotectants in canine semen cryopreservation. For the experiment, pooled semen was submitted to one of the three cryoprotectants, with a final concentration of 3% in egg yolk–TRIS extender. Semen was subjectively evaluated for total and progressive motility, vigour and morphology. Sperm membrane functional integrity was assessed by hypo‐osmotic swelling test (HOST), and longevity was assessed using the thermoresistance test (TRT). Fresh semen showed normal physical and morphological characteristics. After thawing, differences were observed between semen frozen using GL and DF, regarding total and progressive motility and vigour (p < 0.05), but not between MF and GL or MF and DF. Means for total motility, progressive motility, vigour and morphologically normal spermatozoa were, respectively, 69.0 ± 5.4%, 61.0 ± 7.4%, 2.9 ± 0.5 and 57.1 ± 5.0% for GL; 59.0 ± 8.9%, 50.0 ± 10.0%, 2.5 ± 0.7 and 66.9 ± 7.7% for MF; and 44.0 ± 21.0%, 37.0 ± 19.8%, 2.1 ± 0.6 and 61.1 ± 5.5% for DF. On HOST, GL was superior (p < 0.05) to MF and DF (57.8 ± 12.4%, 35.8 ± 18.4% and 34.4 ± 9.4%, respectively). During the TRT, both GL and MF were superior to DF, with no differences between GL and MF. In conclusion, the use of MF as cryoprotectant showed results similar to GL, and can be considered as an alternative in canine semen cryopreservation. Further studies testing different concentrations of MF may improve its effects on cryopreservation of canine semen.     

Analysis of glycosuria in okapi (Okapia johnstoni): Examination of urinary N‐acetyl‐β‐D‐glucosaminidase

We analyzed the urinary excretion of glucose and N‐acetyl‐β‐D‐glucosaminidase (NAG) in six okapis (Okapia johnstoni) in captivity to investigate the cause of their urinary sugar excretion. The urinary glucose‐positive okapi had significantly higher urinary NAG indices than the urinary glucose‐negative okapi. There was also a positive correlation between urinary glucose levels and urinary NAG indices. These results suggest that the proximal tubular function of the glycosuric okapi may have been obstructed, which impaired glucose reabsorption.     

Amantadine in a multimodal analgesic regimen for alleviation of refractory osteoarthritis pain in dogs

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) do not always provide sufficient pain relief in dogs with osteoarthritis (OA). HYPOTHESIS: The use of amantadine in addition to NSAID therapy will provide improved pain relief when compared with the use of nonsteroidal analgesics alone in naturally occurring OA in dogs. ANIMALS: Thirty-one client-owned dogs with pelvic limb lameness despite the administration of an NSAID. METHODS: The study was randomized, blinded, and placebo controlled with parallel groups (days 21-42). On day 0, analgesic medications were discontinued. On day 7, all dogs received meloxicam for 5 weeks. On day 21, all dogs received amantadine (3-5 mg/kg once daily per os) or placebo for 21 days, in addition to receiving meloxicam. Assessments were performed before the study and on days 7, 21, and 42. Primary outcome measures were blinded owner assessments of activity using client-specific outcome measures (CSOM) on days 0, 7, 21, and 42. Data were analyzed by a mixed model approach. RESULTS: For CSOM activity, there was a significant time by treatment effect (P=.009). On the basis of the planned post hoc t-tests of postrandomization means, there was a significant difference between treatment groups on day 42 (P=.030), with the amantadine group being more active. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with osteoarthritic pain refractory to an NSAID, physical activity is improved by the addition of amantadine. Amantadine might be a useful adjunct therapy for the clinical management of canine osteoarthritic pain.     

Atipamezole increases medetomidine clearance in the dog: an agonist—antagonist interaction

Medetomidine, an α₂-adrenoceptor agonist, is a potent sedative and analgesic agent in the dog. When necessary, its action can be effectively antagonized by atipamezole. The present work was designed to study the effects of these drugs on each others' pharmacokinetics when a single intramuscular dose of medetomidine (50 μg kg^-1) was followed by a dose of atipamezole (250 μg kg^-1). Three different treatments were used: medetomidine alone, atipamezole alone, and atipamezole after medetomidine. Drug concentrations in plasma were measured by GC-MS. Statistical analysis of the results (anova) revealed significant differences between treatments in the kinetic parameters of medetomidine. Atipamezole decreased the AUC of medetomidine from 41.3 to 28.6 ng h ml"¹(P = 0.005), t_1/4 from 1.44 to 0.87 h ( P = 0.015), and increased Cl from 21 to 31 ml min^-1kg^-1(P = 0.017). Differences in V₂ did not reach statistical significance. The only statistically significant effects of medetomidine on the pharmacokinetics of atipamezole in this study were the slight decrease of Cl and C _max as well as the increase of AUC . It is suggested that the large dose of medetomidine used caused haemodynamic changes, resulting in decreased hepatic circulation and slower drug metabolism. Antagonism by atipamezole restored the hepatic blood flow and, consequently, increased the elimination of medetomidine by biotransformation.     

Diagnosis and treatment of a chronic atlanto-occipital subluxation in a dog

A 6-year-old Labrador retriever-cross was evaluated for an abnormal gait and head carriage 6 weeks after suffering trauma. The dog was presented with an ambulatory tetraparesis and was reluctant to move his head. Myelography and computed tomography demonstrated a subluxation of the atlanto-occipital joint with compression of the spinomedullary junction and the brain stem by the occipital bone. Removal of the compressive part of the occipital bone resulted in improvement of the clinical signs within 6 weeks, and resolution of clinical signs occurred 8 months after surgery.     

Outcome of a dog undergoing definitive‐intent intensity‐modulated radiation therapy for an intranasal ganglioneuroma

An 11‐year‐old intact male Shiloh Shepherd was presented for evaluation of epistaxis, decreased nasal airflow, and destructive caudal nasal lesion identified using CT. Histopathologic evaluation of the nasal mass was consistent with a ganglioneuroma. The dog was treated with 10 × 4.2 Gy using IMRT technique. Post radiation therapy (RT), improvement in clinical signs were noted. Tumor progressed in size based on CT evaluation at 49 days, 3, and 6 months post‐treatment. A grade 2 oral mucositis was the only RT side effect noted. Radiation therapy as described above was completed without evidence of high‐grade radiation toxicities and has potential to improve clinical signs but failed to induce tumor response.     

Lateral orbitotomy for treatment of an orbital abscess in a dog

A two‐year‐old Jack Russell terrier was diagnosed with a retrobulbar abscess and orbital cellulitis. The diagnosis was confirmed by ultrasound, magnetic resonance imaging examination and ultrasound‐guided fine‐needle aspiration. Transoral ventral drainage was attempted but was unsuccessful. The abscess was successfully treated by open drainage through a lateral orbitotomy. Despite the exposure of the orbital structures, the orbital soft tissues healed by second intention without further complications. The open drainage was well tolerated and resulted in immediate reduction of inflammation and pain, allowing a quick recovery. This report describes the diagnosis and, surgical management and the long‐term (3 years) follow‐up of an unusual case of orbital abscess associated with diffuse periorbital cellulitis successfully treated by open drainage through a lateral orbitotomy.     

Liposome-encapsulated oxymorphone prevents hyperalgesia for 7 days in a rat model of neuropathic pain

A delayed‐release formulation of liposome‐encapsulated oxymorphone (LEO) was produced using a novel dehydration–rehydration technique. Preparations were standardized spectrophotometrically against a known concentration of the drug. The purpose of this study was to test the analgesic properties of LEO in a rat model of neuropathic pain. Sprague–Dawley rats were divided into control (non‐neuropathic) and test (neuropathic) groups. Control and test groups were administered one SC injection of (i) vehicle liposomes (negative control treatment); (ii) liposome‐encapsulated morphine, 2.8 mg kg^?1 (positive control treatment); or (iii) LEO, 1.2 mg kg^?1. All treatments were administered after baseline thermal withdrawal latencies (TWL) were determined (9.2 ± 0.39 seconds (mean ± SEM)). Test groups then underwent sciatic ligation to induce neuropathic pain. TWL were determined in all six groups (n = 8) daily for 1 week. In a separate group of age‐matched rats, blood (0.3 mL from the jugular vein) and urine (1–2 mL via metabolism cages) were collected daily for 7 days after administration of LEO (1.2 mg kg^?1). TWL did not change in the control rats given liposome‐encapsulated sucrose or morphine. There was a small increase (p = 0.04) in TWL in control rats given LEO, likely as a result of the relatively higher dose of oxymorphone compared with morphine based on receptor affinity. TWL in test rats given blank liposomes decreased significantly (p < 0.001) by day 4 (7.1 ± 0.5 seconds), with a maximal decrease by day 7 (5.1 ± 0.36 seconds), indicating development of full hyperalgesia. In contrast, rats given liposome‐encapsulated morphine or oxymorphone had no change in TWL at day 4, indicating that these preparations prevented hyperalgesia after a single injection. This treatment effect persisted through day 7. Serum concentrations of oxymorphone after a single injection of LEO peaked at 4 hours (6.8 ± 0.82 ng mL^?1) and were detectable through day 4 (0.98 ± 0.003 ng mL^?1), while urine concentrations of drug were detectable through day 7. This result suggests that oxymorphone metabolites might have been responsible for the protracted analgesic response. The encapsulation efficiency of oxymorphone using this novel technique was approximately 96%. In conclusion, liposome encapsulation of oxymorphone proved to be an efficient mechanism to provide a delayed‐release formulation of this opioid. This single dose of subcutaneously administered liposome‐encapsulated oxymorphone was effective in preventing hyperalgesia for 7 days in this animal model of neuropathic pain.     

Clinical diagnosis and treatment of suspected neuropathic pain in three dogs

Three dogs were referred to The Queen's Veterinary School Hospital at University of Cambridge for chronic behavioural or locomotor disorders associated with pain. All three had been unsuccessfully treated with conventional analgesics, including non-steroidal anti-inflammatory drugs, glucocorticoids and opiate agonists, prior to referral, with minimal or no response. They were investigated by neurological examination plus conventional ancillary diagnostic tests and therapeutic drug trials. Ruling out other causes of pain and applying previously well-described criteria, each case was diagnosed as consistent with neuropathic pain, a poorly recognised condition in domestic dogs. Treatment with the tricyclic antidepressant drug, amitriptyline, or the antiepileptic drug, gabapentin, resulted in either a dramatic improvement or full resolution of clinical signs in all cases.     

Dacryocystomaxillorhinostomy for chronic dacryocystitis in a dog

A 10-year-old female spayed Vizsla had intermittent mucoid ocular discharge from the right eye for 7 years. History, clinical findings, imaging studies, and culture and histopathology results confirmed chronic dacryocystitis with granuloma. A dacryocystomaxillorhinostomy was performed to preserve the functional portions of the nasolacrimal system remaining in this patient, as well as to promote healing of the lacrimal sac granuloma and secondary infection. Complete resolution of the clinical abnormalities was achieved, and the dog remains healthy 3 years postoperatively.     

Effects of aglepristone, a progesterone receptor antagonist, in a dog with a vaginal fibroma

A 12-year-old, entire, nulliparous crossbreed female dog was presented with a history of vulval bleeding, bulging of the perineum and faecal tenesmus. A firm, non-painful perineal mass, measuring 9.11x5.4 cm, with erythema was detected. Abdominal radiography showed compression and elevation of the rectal ampulla. A dose of 10 mg/kg aglepristone was administered subcutaneously on days 1, 2, 8, 15, 28 and 35. An incision biopsy was taken on day 15 and immunohistochemical analysis showed that the majority of neoplastic cells expressed progesterone receptors. Both the cutaneous erythema and the faecal tenesmus had resolved by day 28. A 50 per cent reduction in size was observed by day 60 (surgical excision). This study shows that benign tumours of the vagina of the dog that contain progesterone receptors can be reduced in size in a palliative or neoadjuvant setting using the progesterone receptor antagonist aglepristone.     

Thymoma‐associated lymphocytosis in a dog

A 9‐year‐old female spayed English Springer Spaniel was evaluated for a cranial mediastinal mass and lymphocytosis. Flow cytometric immunophenotyping of peripheral blood lymphocytes revealed 97% as CD3 positive, confirming a T‐cell lineage. Additionally, T‐cell subset assessment showed 53.2% to be double‐negative T‐lymphocytes, expressing neither CD4 nor CD8 surface markers. The number of double‐negative lymphocytes in circulation coincided with the number of T‐cell receptor (TCR) γδ‐expressing T‐cells in circulation. Molecular T‐cell clonality analysis of TCR Gamma (TCRG) gene rearrangement showed a polyclonal expansion of T‐lymphocytes. Histopathology confirmed the mass to be a thymoma, supporting the diagnosis of thymoma‐associated T‐cell lymphocytosis. Resolution of the lymphocytosis after removal of the thymoma provided further evidence for this diagnosis. To the authors' knowledge, this case is only the second report of thymoma‐associated peripheral lymphocytosis in the veterinary literature, and is the first to report a confirmed thymoma‐associated peripheral γδ T‐cell lymphocytosis in a dog.     

Massive uric acid crystalluria and cylinduria in a dog after l‐asparaginase treatment for lymphoma

A 10‐year‐old golden retriever bitch was treated for diarrhea and vomiting that lasted about 1 month without a specific diagnosis until a hepatic biopsy provided a histopathologic diagnosis of lymphoma. The dog was referred to the Swedish University of Agricultural Science and treated with one dose of l ‐asparaginase. The day after chemotherapy, the urine was dark yellow, very turbid, and had large amounts of small amorphous crystals and many casts made of similar appearing material identified by infrared spectroscopy to be 100% uric acid dihydrate. Serum uric acid was elevated at 224 μmol/L (RI 0‐59). The dog's illness became worse after chemotherapy. Lymphoma treatment was not continued, and the dog was euthanized 9 days after the l ‐asparaginase treatment. Among other problems were persistent proteinuria with a urine protein‐to‐creatinine ratio of 2.3 and severe hypoalbuminemia. Serum protein electrophoresis performed 3 weeks prior to chemotherapy indicated hyperproteinemia (total protein 78 g/L) having a biclonal gammopathy with 35 g/L β‐2 globulins and 11 g/L γ globulins. Despite prominent cylinduria and crystalluria, the patient did not develop azotemia or isosthenuria.