Reduction of allodynia in patients with complex regional pain syndrome: A double-blind placebo-controlled trial of topical ketamine

Abstract

Venous blood for plasma estimations of ketamine and norketamine was obtained one hour after application of the creams. Ketamine applied to the symptomatic limb inhibited allodynia to light brushing and hyperalgesia to punctate stimulation.Systemic effects of the ketamine are unlikely to account for this as plasma levels were below detectable limits. As touch thresholds were unchanged, NMDA receptors may contribute to sensory disturbances in CRPS via actions at cutaneous nociceptors.Allodynia and hyperalgesia were detected in the ipsilateral forehead to a range of stimuli (brushing, pressure, punctate stimulation, cold, heat, warmth). In several patients, ketamine treatment of the symptomatic limb inhibited allodynia to brushing the ipsilateral forehead, suggesting that the mechanism that mediates allodynia in the symptomatic limb contributed to allodynia at more remote sites. The present study shows promise for the use of topical ketamine as opposed to parenteral and oral forms which often result in undesirable side effects.

Transdermal Ketamine and S(+)-Ketamine as Adjuvants Following Orthopaedic Surgery under Bupivacaine Spinal Anaesthesia

“…The analgesic action of transdermal ketamine or S(+)-ketamine analgesia could be due to a central effect, a peripheral effect [20][21][22] or both, secondary to its plasmatic absorption [1,[7][8][9][10][11]. Studies in volunteers described the isomer S(+)-ketamine as a potent analgesic at already low plasma concentrations [23], even at sub anaesthetic plasmatic doses [24].…”

“…As an example, the topical application of a compounded amitriptyline-ketamine formulation improved pain in 75% of patients suffering from erythromelalgia [6] and the use of topical 10% ketamine, might be a useful tool for the treatment of Hidradenitis Supprurativa pain [7]. Proposed mechanisms of ketamine´s analgesia are controversial and include blockade of N-methyl-D-aspartate receptors in a non-competitive fashion [7], analgesia secondary to the absorption of topical ketamine into circulation [1,[8][9][10][11][12], resulting in attenuation of central sensitization [10], or peripheral mechanism of action [13] at cutaneous nociceptors [14].…”

Topical Treatment in Pain Medicine: From Ancient Remedies to Modern Usage

“…[141,142,147] Long-term effects on the urinary tract [155] may be circumvented by the use of topically applied ketamine, which results in low plasma levels of the drug. [156] Nevertheless, as with some other topical drugs, inappropriate or excessive use can lead to significant toxicity. [157] Combinations of drugs for topical application can be used for treatment of some …”

The Use of Ketamine in Neuropathic Pain

“…While the majority of ketamine use in CRPS research has studied intravenous administration, Finch et al [95] studied the use of topical 10 % ketamine in patients with CRPS in a randomized, crossover, placebo-controlled study of 20 CPRS patients. There was no significant pain reduction in the topical ketamine group.…”