Topical Compounded Analgesic Treatment in Neuropathic Pain: 8 years of Experience

Abstract

In our tertiary referral centre, the Institute for Neuropathic Pain, we have treated many patients suffering from localized peripheral neuropathic pain since 2009. We have developed, together with a compounding pharmacist, a base cream as a topical formulation which has enabled us to compound creams based on amongst others amitriptyline, ketamine, clonidine, baclofen, and phenytoin. We have found that many patients profit from such topical formulations and we will describe our experiences using such creams over the last 8 years in this paper, since we first started exploring such topical treatments. We have analysed the efficacy and safety of these topicals, and based on literature, our own online data pool and the patients who had let us know that they benefited from the creams, found sufficient analgesia and positive effects impaired sleep, while the tolerability was excellent. Patients suffering from localized peripheral neuropathic pain, as in diabetic neuropathy, chronic idiopathic axonal polyneuropathy, chemotherapy induced polyneuropathy and small fiber neuropathy, as well as in complex regional pain syndrome, seem especially responsive to such topical approach. Meanwhile, more than 800 Dutch medical doctors have been prescribing one or more of our compounded creams, and patients and medical doctors from abroad frequently contact us to explore the therapeutic options for their patients based on these creams.

Rediscovery of old drugs: the forgotten case of dermorphin for postoperative pain and palliation

“…For a number of years, we have been quite interested in the repositioning of old drugs, especially subsequent to finding topical phenytoin, ketamine, baclofen, and loperamide effective in alleviating neuropathic pain. 1 We have since concentrated on the repositioning of an old molecule, phenytoin, forgotten as an analgesic. 2 We found phenytoin to be quite valuable for the treatment of localized peripheral neuropathic pain, for conditions including painful diabetic neuropathy, chemotherapy induced neuropathy, small fiber neuropathy, and chronic idiopathic axonal neuropathy.…”

“…The discovery, characterization, and isolation of a new opioid receptor agonist, dermorphin, in the dermal secrete of a specific Amazon frog ( Phyllomedusa sauvagei ) in 1981 by Montecucchi et al from the renowned Italian research group of Vittorio Erspamer (1909–1999), was groundbreaking. 4 It was directly recognized by Erspamer and his colleagues that this heptapeptide possessed “exceptionally intense and long-lasting peripheral and central opiate-like actions.” 1 They, therefore, named the compound dermorphin, derived from the words “derm” and “morphine.” 1 The structure was elucidated as heptapeptide dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), and the position of a D-amino acid in this heptapeptide was quite remarkable. The group was captured by dermorphin and its peptide family, and in 1981 stated that it had become the object of nonstop work by them over the previous 2 years.…”

Topical phenytoin formulations for pain in small fiber neuropathy, a pathogenetic approach

“…Topical phenytoin, a non-selective sodium channel blocker used in an ex juvantibus approach to detect responders In the last 8 years we have developed many compounded topical formulations containing active compounds such as ketamine, clonidine, amitriptyline and baclofen [17]. Since some years we optimized one specific formulation containing phenytoin, because we were impressed by its efficacy in case series, and phenytoin could be easily combined with the other (co-)analgesics in a base vehicle cream [18].…”