Topical Compounded Ketamine
A Useful Agent for Neuropathic Pain
Patients often suffer with continued neuropathic pain even after the typical medications have been prescribed. Prescribers can consider topical agents as an alternative in the analgesic regimen. While the more common topical analgesics include capsaicin and lidocaine, other medications can provide different types of analgesic activity such as excitatory mediators, peripheral afferents, and inhibitory influences. Topical analgesics have many advantages over systemically administered medications. The reduction or elimination of side-effects stands chief among these advantages. Topical analgesics differ from transdermal delivery methods in that prescribers use topical applications to deliver local, rather than systemic, effects. Our practice, The Center for Musculoskeletal & Pain Medicine, uses a variety of custom-compounded agents to improve your patients’ experience with pain.
One of the custom compounds useful for some patients is a topical ketamine cream. Peripheral N-methyl-D-aspartate (NMDA) receptors have been implicated in nociception.1-3 Ketamine blocks NMDA and 5HT receptors, Na+ and Ca+ channels, and the edema response associated with inflammation. Topical ketamine applications have documented success with neuropathic pain in terms of providing some direct analgesia and in terms of inhibiting sympathetically maintained pain. However, the most important use of custom-compounded ketamine cream is the reduction of hyperalgesia (an exaggerated sensation after a painful stimulus), the reduction of allodynia (a painful sensation elicited by a nonpainful stimulus), and as a tolerance-protective agent.4-12 The literature describes topical ketamine applications as being useful for pain management in cases of post-surgical neuropathic pain, complex regional pain syndrome, lumbar radiculopathy, post-herpetic neuralgia, and idiopathic proctodynia.
In 2006, Poyhai and Vainio proposed that ketamine cream worked by being absorbed into the bloodstream and reducing central sensitization.7 However, the evidence collected by Finch and colleagues (Pain 2009), suggests that ketamine cream acts only locally.4 After applying a 10% ketamine cream compound, they could not find evidence of ketamine in the bloodstream for 20 patients, and ketamine applied to healthy limbs produced no effect in painful limbs. Custom-compounded ketamine creams have no documented side effects.
We introduce the subject of custom-compounded topical ketamine as an illustration of the many considerations and possibilities available in pain management.
- 1Chizh B, Headley P, NMDA antagonists and neuropathic pain: multiple drug targets and multiple uses. Curr Pharm Des 2005; 23: 2977-94.
- Trist D. Excitatory amino acid agonists and antagonists: pharmacology and therapeutic applications. Pharm Acta Helv 2000; 74: 221-9.
- Sang C. NMDA-receptor antagonists in neuropathic pain: experimental methods to clinical trials. J Pain Symptom Manage. 2000; 19: S21-S25.
- Finch P, Knudsen L, Drummond P. Reduction of allodynia in patients with complex regional pain syndrome: A double-blind, placebo-controlled trial of topical ketamine. Pain. Nov 2009; 146 (1-2): 18-25.
- Lehman J, Sciallis G. Effective use of topical amitriptyline hydrochloride 2.5% and ketamine hydrochloride 0.5% for analgesia in refractory proctodynia. J Drugs Dermatol. 2008; 7 (9): 8887-9.
- Visser E, Schug S. The role of ketamine in pain management. Biomed Pharmacother. 2006; 60: 341-348.
- Poyhia R, Vainio A. Topically administered ketamine recduces capsaicin-evoked mechanical hyperalgesia. Clin J Pain. 2006; 22 (1): 32-6.
- Ushida T, Tani T, Kanbara T, et al. Analgesic effects of ketamine ointment in patients with complex regional pain syndrome type 1. Reg Anesth Pain Med. 2002; 27(5): 524-8.
- Gammaitoni A, Gallagher R, Welz-Bosna M. Topical ketamine gel: possible role in treating neuropathic pain. Pain Med. 2000; 1(1): 97-100.
- Warncke T, Jorum E, Stubhaug A. Local treatment with N-methyl-D-aspartate receptor antagonist ketamine, inhibits development of secondary hyperalgesia in mang by a peripheral action. Neurosci Lett. 1997; 227:1-4.
- Pederson J, Galle T, Kehlet H. Peripheral analgesic effectsof ketamine in acute inflammatory pain. 1998; 89: 58-66.
- Crowley K, Flores J, Hughes C, et al. Clinical application of ketamine ointment in the treatment of sympathetically maintained pain. Int J Pharmaceut Compound. 1998; 2: 122-127.