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Pain Management

Grapiprant: an EP4 prostaglandin receptor antagonist and novel therapy for pain and inflammation.

Summary:

There are five active prostanoid metabolites of arachidonic acid (AA) that have widespread and varied physiologic functions throughout the body, including regulation of gastrointestinal mucosal blood flow, renal haemodynamics and primary haemostasis. Each prostanoid has at least one distinct receptor that mediates its action. Prostaglandin E2 (PGE 2) is a prostanoid that serves important homeostatic functions, yet is also responsible for regulating pain and inflammation. PGE 2 binds to four receptors, of which one, the EP4 receptor, is primarily responsible for the pain and inflammation associated with osteoarthritis (OA). The deleterious and pathologic actions of PGE 2are inhibited in varying degrees by steroids, aspirin and cyclo-oxygenase inhibiting NSAIDs; however, administration of these drugs causes decreased production of PGE 2, thereby decreasing or eliminating the homeostatic functions of the molecule. By inhibiting just the EP4 receptor, the homeostatic function of PGE 2 is better maintained. This manuscript will introduce a new class of pharmaceuticals known as the piprant class. Piprants are prostaglandin receptor antagonists (PRA). This article will include basic physiology of AA, prostanoids and piprants, will review available evidence for the relevance of EP4 PRAs in rodent models of pain and inflammation, and will reference available data for an EP4 PRA in dogs and cats. Piprants are currently in development for veterinary patients and the purpose of this manuscript is to introduce veterinarians to the class of drugs, with emphasis on an EP4 PRA and its potential role in the control of pain and inflammation associated with OA in dogs and cats.

Author & Journal:Kirkby Shaw K, et al, Vet Med and Science 2015
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Evaluation of electroacupuncture treatment for thoracolumbar intervertebral disk disease in dogs

Summary:

To evaluate use of electroacupuncture combined with standard Western medical treatment versus Western medical treatment alone for treatment of thoracolumbar intervertebral disk disease in dogs.

Conclusion:

Electroacupuncture combined with standard Western medical treatment was effective and resulted in shorter time to recover ambulation and deep pain perception than did use of Western treatment alone in dogs with signs of thoracolumbar intervertebral disk disease.

Author & Journal:Hayashi AM, et al, J Am Vet Med Assoc 231(6):913-918, 2007
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Pharmacokinetics of intravenous and oral amitriptyline and its active metabolite nortriptyline in Greyhound dogs.

Summary:

To evaluate the pharmacokinetics of amitriptyline and its active metabolite nortriptyline after intravenous (IV) and oralamitriptyline administration in healthy dogs.

Conclusion:

Amitriptyline at 4 mg kg(-1) administered orally produced low amitriptyline and nortriptylineplasma concentrations. This brings into question whether the currently recommended oral dose of amitriptyline (1-4 mg kg(-1)) is appropriate in dogs.

Author & Journal:Norkus C, et al, Vet Anaesth Analeg 2015;42:580-589
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Evaluation of a Single Intra-Articular Injection of Autologous Protein Solution for Treatment of Osteoarthritis in a Canine Population.

Summary:

To evaluate the safety and efficacy of an intra-articular injection of autologous protein solution (APS) for treatment of canine osteoarthritis (OA).

Conclusion:

APS injection reduced pain and lameness scores and increased weight-bearing associated with the OA-affected joint in dogs at 12 weeks providing preliminary evidence that APS therapy may be beneficial in the treatment of OA in dogs and supporting pursuit of additional studies.

Author & Journal:Wanstrath AW, et al, Vet Surg 2016;45:764-774
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A Prospective, Randomized, Masked, Placebo-Controlled Multisite Clinical Study of Grapiprant, an EP4 Prostaglandin Receptor Antagonist (PRA), in Dogs with Osteoarthritis.

Summary:

This study evaluated the effectiveness and safety of grapiprant for treatment of pain in dogs with osteoarthritis (OA).

Conclusion:

Grapiprant is an effective treatment for alleviation of pain in dogs with OA, and represents a modality of treatment that may be better tolerated than current options.

Author & Journal:Rausch-Derra L, et al, J Vet Intern Med 2016
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Double-blind evaluation of implants of gold wire at acupuncture points in the dog as a treatment for osteoarthritis induced by hip dysplasia.

Summary:

Thirty-eight dogs with hip dysplasia were studied to evaluate the use of gold wire implants at acupuncture points around the hip joints.

Conclusion:

Radiographs were taken at the beginning and end of the study. Although the data collected from both groups by the veterinarians and the owners showed a significant improvement of locomotion and reduction in signs of pain (P=0.036 for the veterinary evaluation and locomotion and P=0.0001 and P=0.0034 for the owners’ evaluation of locomotion and pain, respectively), there were no statistically significant differences between the treated and control groups (P=0.19 and P=0.41, P=0.24, respectively).

Author & Journal:Hielm-Bjorkman A, et al, Vet Rec 149(15):452-456, 2001
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Clinical diagnosis and treatment of suspected neuropathic pain in three dogs.

Summary:

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.

Conclusion:

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.

Author & Journal:Cashmore RG, et al, Aust Vet J 2009;87:45-50
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Adipose tissue derived mesenchymal stem cells for musculoskeletal repair in veterinary medicine.

Summary:

This review focuses on the characterization of ASCs for their use for tissue engineering approaches especially in veterinary medicine and also highlights a selection of clinical trials on the basis of ASCs as the relevant cell source.

Author & Journal:Arnhold S, et al, Am J Stem Cells 2015;4:1-12
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