Table 4: Unlicensed drugs used in the medical management of CM-P and SM-S
DrugDose *Notes and adverse effects
Analgesics
NSAIDsAs per data sheetInhibit production of prostaglandins through actions on cyclooxygenase (COX) pathway.
NSAIDs can result in vomiting and diarrhoea; however, an animal that has an adverse reaction to one drug will not necessary react to another. Not recommended for animals with kidney disease. Small risk that NSAIDs may precipitate heart failure in animals with pre-existing heart disease
Paracetamol (acetaminophen)10 mg/kg PRN up to TIDCentral analgesic effect mediating descending serotonergic pathways either through inhibition of prostaglandin synthesis or through metabolite influencing cannabinoid receptors (Anderson 2008). This drug has been found to be useful for ‘break-through’, short-term pain management (ie, allowing the owner to ‘top-up’ existing pain relief). Potential for renal, hepatic, gastrointestinal, and haematologic (methemoglobinaemia) adverse effects. High doses can cause keratoconjunctivitis sicca (dry eye). Use this drug with caution as dogs do not metabolise it as well as people. It is highly toxic to cats so do not use in this species
Adjuvant analgesics
Gabapentin10–20 mg/kg BID/TIDFirst-generation α2δ ligand (inhibits excitatory voltage-dependant calcium channels). Can result in mild sedation and poor coordination, especially when therapy is first started. May increase appetite and increased calorific intake may result in weight gain. Therapy should not stop suddenly (ie, the drug should be withdrawn slowly). Avoid xylitol-containing suspensions
Pregabalin5–10 mg/kg BID/TIDSecond-generation α2δ ligand (inhibits excitatory voltage-dependant calcium channel). Can result in mild sedation and poor coordination, especially when therapy is first started. May increase appetite and increased calorific intake may result in weight gain. Therapy should not stop suddenly (ie, the drug should be withdrawn slowly)
Topiramate10 mg/kg TIDAntiepileptic drug with multiple possible mechanisms of action, including carbonic anhydrase inhibition. Little information available for this drug. It should be avoided or used with caution in patients with hepatic or renal disease. The most common adverse effect is sedation and ataxia, which is more likely with polypharmacy. Gastrointestinal adverse effects including inappetence/anorexia may be seen. Irritability, aggression, chewing of digits and facial rubbing have be reported
Amantadine3–5 mg/kg PO SIDN-methyl-d-aspartate (NMDA) antagonist which may reduce nociceptive activation as adjunctive therapy (ie, with another drug). Little information available for this drug. The most common adverse effect is sedation and ataxia, which is more likely with polypharmacy. Agitation or gastrointestinal adverse effects may be seen. It should be avoided or used with caution in patients with glaucoma, hepatic disease, renal disease, congestive heart failure, atopic dermatitis or seizure disorders
Memantine0.3–1 mg/kg BIDNMDA antagonist which may reduce nociceptive activation as adjunctive therapy. Very little information for this drug; its use in dogs has been described in compulsive disorder, but not pain (Schneider and others 2009). Its advantage over amantadine is lower cost and a tablet formulation. Systemic review and meta-analysis in human studies suggests it has the potential to decrease pain, but adverse effects of dizziness are common (Kurian and others 2019). Potential adverse effects in dogs include ataxia, tremor and seizures
Amitriptyline0.25–2 mg/kg PO SID/BIDTricyclic antidepressant blocking re-uptake of serotonin and norepinephrine neurotransmitters. The most common adverse effect is sedation, which is more likely with polypharmacy. Other possible adverse effects include hyperexcitability, seizures, dysrhythmias, bone marrow suppression, diarrhoea, vomiting, hypersalivation. Not advised in animals with seizures or epilepsy. Caution in patients with thyroid disorders, urinary retention, hepatic disorders, keratoconjunctivitis sicca, glaucoma, cardiac rhythm disorders or diabetes
(Possible) CSF-reducing drugs
Omeprazole0.5–1.5 mg/kg PO SID/BIDInhibitor of H+/K+-activated ATPase (in the choroid plexus Na+/K+-ATPase regulates the production of CSF). In laboratory rodents long-term therapy reported to result in changes to the stomach lining. However, this effect has not been reported in dogs. Reported adverse effects include nausea, diarrhoea constipation and skin rashes
Cimetidine5–7 mg/kg PO TIDHistamine H2 receptor antagonists (epithelial cells of the choroid plexus possess histamine H2 receptors). Adverse effects with this antacid are rare even at high doses. Liver and kidney toxicity have been reported. In people, cimetidine has been reported (rarely) to be associated with headache. Cimetidine may increase the kidney clearance of gabapentin
(Possible) CSF-reducing drugs continued
Acetazolamide4–8 mg/kg SIDCarbonic anhydrase inhibitor (enzyme involved in CSF secretion). Adverse effects are common especially with long-term use and may include anorexia, gastrointestinal signs, bone marrow depression, metabolic derangement (hypokalaemia, hypochloraemia, hyponatraemia, hyperglycaemia), hepatic insufficiency, hypersensitivity reactions (eg, rash) and CNS signs (sedation, depression, weakness, excitement).
Corticosteroids
Prednisone/ Prednisolone/ methylprednisolone0.5 mg/kg PO SID
then decrease to lowest possible, ideally alternate day, dose that controls signs
Neuroactive steroids modulate pain sensitivity and reduce neuropathic pain. Possible effect on aquaporin-4 expression (water channels) in spinal cord. An option for severe SM-S-associated weakness or phantom scratching. However, long-term use is not recommended due to adverse effects. Chronic use results in muscle loss, thereby increasing weakness and animals are often lethargic and heat intolerant; signs which are easily confused with CM-P and SM-S.Other possible adverse effects include: vomiting; diarrhoea; increased urination and drinking and when combined with diuretics can result in potassium depletion; increased appetite and increased calorific intake that results in weight gain; skin changes and poor hair growth; delayed wound healing and increased susceptibility to infection. This drug should not be given to patients that are pregnant, have diabetes mellitus or kidney disease.
Cannabinoids
Cannabidiol (CBD oil/hemp extract)2 mg/kg BID#Cannabinoids act via cannabinoid receptors and affect the activities of many other receptors, ion channels and enzymes. They inhibit release of neurotransmitters and neuropeptides from presynaptic nerve endings, modulate postsynaptic neuron excitability, activate descending inhibitory pain pathways and reduce neural inflammation. Cannabinoids appear to be well tolerated in dogs. Serum biochemistry may show an increase in alkaline phosphatase, presumed due to liver enzyme induction.
  • BID Twice a day, CM-P Chiari malformation-like associated pain, CNS Central nervous system, CSF Cerebrospinal fluid, PO Per os (orally), SID Once a day SM-S Syringomyelia-specific signs

  • *Dose I use. Unless otherwise indicated, start at the low end of the dose range and make increases based on effect and absence of adverse effects. Effect is assessed over a two to four-week period, except for amantadine, memantine and amitriptyline which require at least four weeks of use to assess effectiveness. Assessment of haematology and biochemistry is recommended before starting and at least annually for animals receiving long-term medication. Gabapentin and pregabalin are Schedule 3 controlled drugs under the Misuse of Drugs Regulations 2001 and Class C of the Misuse of Drugs Act 1971

  • #Dose based on the only published canine study (Gamble and others 2018) assessing CBD oil for pain associated with osteoarthritis; however, most commercial preparations do not contain enough compound to be able to achieve this dose. The UK Veterinary Medicines Directorate considers that veterinary products containing cannabidiol are veterinary medicines and therefore can only be administered with a veterinary prescription