Ethical justification of single-blind and double-blind placebo-controlled response tests in neuropathic pain and N-of-1 treatment paradigm in clinical settings.

At our center in the Netherlands, patients, who very often are treatment resistant to the analgesics recommended in the guidelines, suffering from symmetrical peripheral neuropathic pain are treated exclusively. We have developed a number of compounded topical formulations containing classical co-analgesics such as ketamine, baclofen, amitriptyline, and phenytoin for the treatment of neuropathic pain in treatment-resistant patients. In order to identify putative responders and exclude an (initial) placebo-response, we developed single-blind and double-blind placebo-controlled response tests. The test can be performed when the patient has a symmetrical polyneuropathy with a pain score difference of not more than 1 point on the 11-point numerical rating scale (NRS) between bilateral pain areas. On one area (eg, left foot) the placebo cream and on the other area (eg, right foot) the active cream will be applied. Within a time frame of 30 minutes, patients are considered responders if they rate a pain difference of at least 2 points on the NRS between the bilateral areas on which the active cream and placebo cream are applied. Response tests can be easily conducted during the first consultation. In this paper, we explore the ethical context of using a placebo in clinical practice in a single-blind and double-blind fashion to improve and individualize treatment of neuropathic pain outside a context of a formal clinical trial.

Skin matters! The role of keratinocytes in nociception: a rational argument for the development of topical analgesics.

Treatment of neuropathic pain using topical formulations is still in its infancy. Only few topical analgesic formulations have become available for clinical use, and among these, analgesic creams are still rare. This is unfortunate because analgesic creams offer a number of advantages over patches, such as convenience, ease of adapting the frequency of application, and dose, and "rubbing cream where it hurts" involves the patient much more in the therapeutic process compared to patches and other localized treatment modalities. Although the literature supporting the efficacy and safety of analgesic creams (mostly compounded) is growing since the last decade, most pain physicians have not yet noticed and appreciated the therapeutic potential and clinical value of these creams. This is most probably due to a prejudice that topical application should need to act transdermally, more or less as a slow-release formulation, such as in patches delivering opioids. We will discuss this prejudice and show that there are multiple important targets in the skin to be reached by topical analgesic or anti-inflammatory compounds, and that the keratinocyte is one of those targets. By specifically targeting the keratinocyte, analgesia seems possible, effective, and safe, and thus topical analgesic creams may hold promise as a novel treatment modality for neuropathic pain.

Interventional management of cancer pain.

PURPOSE OF REVIEW: Interventional techniques were the mainstay for cancer pain management before the WHO ladder and opioids were freely available. The three-step WHO ladder has its limitations, and cancer pain is often under treated. Advances in treatment options mean that cancer patients are living longer and pain interventions may have a role to play even early in the cancer diagnosis for better quality of analgesia. The role of high doses of opioids in pain management is also currently under scrutiny. RECENT FINDINGS: Recent advances in intrathecal analgesia, radiofrequency techniques, both in tumour ablation and neurotomies, are being widely used for palliation. Vertebroplasty techniques have been used not only for pain relief, but also for stabilization. Improved imaging and thoracoscopic techniques have made coeliac plexus and splanchnic blockade safer and more efficacious. There has been recent interest in percutaneous cordotomy with newer techniques using computed tomography/MRI and endoscopy guidance. Percutaneous electrical nerve stimulation and 8% capsaicin patches have been successfully used for managing neuropathic pain in cancer. SUMMARY: Interventions form an integral part in providing pain relief in complex cancer pains. Oncologists and palliative care physicians are to be educated on the usefulness and timing of interventions in the management of complex cancer pain.