Using the epidural route for more targeted delivery of therapeutics in dogs with spinal cord injury

ADMINISTRATION of medications into the epidural space was first performed more than 100 years ago when cocaine was administered epidurally to dogs to explore its potential for analgesia of the limbs and genitourinary system in people.1 Since then, epidural application of local anaesthetics and opioids has become a well-established means of providing analgesia during veterinary procedures involving the chest, abdomen, pelvis or pelvic limbs.2, 3 In addition to opioids such as morphine and local anaesthetics such as bupivacaine or lidocaine, various other medication classes can also be delivered by the epidural route, including corticosteroids such as methylprednisolone, α-2 agonists such as dexmedetomidine and muscle relaxants such as baclofen. Administering these medications epidurally rather than via indirect routes (eg, intravenously or orally) provides more targeted delivery to the spinal cord or the nerve roots, facilitating higher local drug concentrations and potentially reducing unwanted systemic effects.2, 4 In the past few decades, the use of epidurally administered therapeutics to manage neurological conditions in dogs has also begun to be explored. In particular, epidural steroid injections have been increasingly used in clinical cases of lumbosacral stenosis, with reported short-lived improvement in as many as 84.4 per cent of cases following a single application.5, 6 Epidural delivery of methylprednisolone acetate at the time of decompressive surgery can significantly reduce the time taken to regain ambulation in dogs with paraplegia secondary to intervertebral disc disease The study by Natsios and colleagues, summarised on p 188 of this issue of Vet Record, sought to address this knowledge gap by assessing the time to ambulation in non-ambulatory dogs with IVDD that received epidural ‘splash’ application of either methylprednisolone acetate (1 mg/kg, n=18) or saline (n=23) at the time of decompressive surgery.12 They found a significant difference in time to ambulation between the two treatment groups, with the methylprednisolone acetate group achieving ambulation in a median of three days compared with seven days in the saline group. Although infection is a known risk of epidural medication delivery,13 only a single case of abscess formation and discospondylitis was observed (in a dog in the methylprednisolone acetate group).12 Natsios and colleagues speculated that this complication may have been attributable to the immunosuppressive effects of the steroid treatment.12 A herniated disc not only results in mechanical compression and the chemical irritation of spinal nerves but also induces an epidural inflammatory response, ranging from acute invasion of neutrophils to the formation of chronic granulation tissue.14 This inflammation in the epidural compartment induced by a herniated disc is increasingly recognised as playing a pivotal role in the course and outcome of IVDD. Therefore, as discussed by Natsios and colleagues,12 steroids like methylprednisolone have the potential to help promote faster recovery of spinal cord conduction by mitigating the SCI-associated inflammatory response. Although intravenous methylprednisolone administration has been found to have no beneficial effect when given to dogs with IVDD following decompressive surgery,15-18 the findings of Natsios and colleagues' study suggest that the epidural application of methylprednisolone at the time of decompressive surgery would improve outcomes in non-ambulatory dogs with intact nociception.12 Future prospective studies involving more severely affected cases without deep pain perception, where a return to ambulation is less assured, would also be valuable to build a more complete picture of the clinical value of epidural methylprednisolone in dogs with IVDD. Stem cell transplantation strategies are another promising new therapeutic approach for treating SCI in dogs with IVDD, and several experimental studies have already investigated the safety and efficacy of epidural application of canine adipose tissue or amniotic-membrane derived mesenchymal stem cells in dogs with paraplegia secondary to natural acute or chronic thoracolumbar myelopathy.19-21 The results of these studies suggest that epidural stem cell transplantation is safe, but they do not show clear evidence of improvements in dogs' recovery. Despite this, one study did indicate a faster improvement in locomotor function in dogs receiving stem cell transplantation.19 However, it should be noted that none of these studies had a rigorous, randomised, blinded, case-control design. Prospective randomised blinded studies, such as that performed by Natsios and colleagues,12 are paramount in the future exploration of the epidural route for delivery of new therapeutic products for dogs with SCI. In conclusion, proximal and site-specific routes of administration to the spinal cord, such as the epidural or intrathecal routes, are beneficial for delivering both established and novel therapeutic interventions in dogs with SCI. Epidural administration of therapeutics has the potential to significantly improve clinical outcomes in dogs with SCI by accelerating recovery processes and enhancing therapeutic efficacy.