Topical analgesics, topiceuticals: Why Skin Matters
Why Skin Matters was the title of a series lectures at the 8th EFEC meeting on pain in Florence, 2013.
Prof. Pappagello opened the symposium and presented a useful overview, he spoke of ‘The age of topiceutcals or Think out of the pill box’. He emphasized that it is extremely important for clinicians to understand the relevance of topical treatments, both on the level of efficacy and side-effects/tolerability.
Why intoxicate patients with systemic drugs, professor Pappagello asked, if the problem is regional? Many patients suffering from regional neuropathic pain are frail and older, and already have more than one drug orally. Topical analgesia: the skin as an important new inroad in treating chronic pain! This reduces side effects while remaining effective.
Indications for topical treatment
Pappagello focussed on some examples of useful topical therapies, such as various neuropathic pain conditions such as painful diabetic neuropathy. Postsurgical neuropathic pain is also an important issue, much unrecognized, and very much suited to be treated topically. Other relevant indications are chemotherapy induced neuroathic pain, rising in prevalence, CRPS, herpes pain and HIV neuropathic pain. For all these indications topical treatment is indicated.
Topicals: 13 classes of analgesics, from lidocaine to palmitoylethanolamide
Topical analgesics overview
There are 13 classes of analgesics used and evaluated for topical use, for which at least some evidence exists. Only for the subsection of topical anesthesia there are already 10 different preparations available, from prilocaine up to lidocaine. Topical treatment with lidocaine plasters are advocated more and more. Cacaicine from low dose (0,025) up to 20% concentration is used to kill off the small fibres in the skin. An alphablocker as clonidine is currently developed as ARC-4558 topical is as 0.1 % gel and patch.
Botulinum toxin is also under evaluation as a topical preparation. Furthermore the old drugs amitriptyline and ketamine creams are compounded in creams. NSAIDs are also formulated in topicals, such as diclofenac gel, patches, creams and lotion. Baclofen is also evaluated in one small RCT in chemo-induced PNP, and DMSO50% in CRPS ( conflicting results, perhaps effective in warm CRPS). The next cream discussed was based on a heavy metal, strontium cloride 4%. This topical salt cream were effective in itch, as demonstrated in a RCT.
Palmitoylethanolamide: new kid on the block
Topical analgesics: the value of palmitoylethanolamide
Palmitoylethanolamide (PEA) was also discussed as being an useful compound for topical aplication. PEA is autocoid, and it was pointed out by the speaker that this molecule might also be important as a topical analgesic. It has a totally different mode of action, being the activation of endogenous anti-inflammatory and anti-pain mechanisms, among which via the nuclear receptor PPAR alpha. Its tolerability is documented and impressive. This year (2013) such a topical creme will become available, produced on the base of 1.5% palmitoylethanolamide cream (PeaPure cream).
Skin: an important window of opportunities for toipical analgesics
Taken together, the skin presents an important window of opportunity to treat neuropathic pain, and should be consudered much more. Especially since it is arm in side effects and can be easily combined with other analgesic treatment modalities.
Professor Pergolizzi from the Universities of Harvard and Parma presented the physiology of the skin and the importance of skin as a route for pain treatment. There is a fundamental difference between a topical and a trans dermal formulation. The skinis is a valuable tool in which to apply multi-multimolecular intervention, was stressed by this speaker.
He stipulated that compounded creams can directly be used, with few side effects and pointed out that we need to think differently about topicals, especially since more and more proof is gathering for its optimal balance between efficacy and side effects. Topical analgesics act through peripheral mechanisms relevant for chronic pain. Transdermaly formulations need to get the drug into the bloodstream, such as buprenorphine and are always controlled pharmacokinetic systems, medical devices.
Presentation of the Dutch INP creme’s during the EFIC 2013
During the discussion professor Keppel Hesselink from the Institute of Neuropathic Pain was invited on the stage to share the Dutch experience with topical creams. He explained that topical creams need to be formulated in such a cream formulation, so that the concentration of active compounds is high, for instance 10% ketamine or 10% amitriptyline. He also explained that in the Netherlands the Institute works with such topical creams already for years, and the selection of a different cream base than PLO helped quite a bit in creating stable cream, which is suited for combining various analgesics, including creams containing baclofen, clonidine and palmitoylethanolamide.