Palmitoylethanolamide for the treatment of centralised chronic pain

Chronic low level inflammation within the central nervous system (CNS) is increasingly being recognised as a potential contributor to many types of persistent pain. Through the activation of glia, especially microglia and astrocytes, it is thought that alterations in synaptic function lead to changes in the way that pain is processed within the CNS. It is believed that these changes play a significant part in the development of central sensitisation. There is also evidence that this glial activation may also account for many of the neuro-vegetative features common in persistent pain such as anxiety, depression, fatigue, poor sleep and cognitive problems. It is hoped that medicines that are able to suppress CNS inflammation might help relieve pain, improve function and associated psychiatric symptoms in patients with chronic pain. Palmitoylethanolamide (PEA) is a naturally occurring fatty acid involved with known anti-inflammatory properties and has been suggested to be involved in the regulation and termination of inflammatory responses within the CNS. It is currently classed as a nutraceutical and available from compounding chemists without prescription. There is some evidence that administration of PEA has analgesic benefits in a variety of causes of persistent pain, although evidence is limited by significant industry support. It does have anecdotal evidence of positive effects and appears to be very well tolerated, with a low risk of serious adverse effects. Given the limitations in current pharmacologic options in the management of persistent pain, it represents a potential useful addition to the current therapeutic options. The aim of this study is to assess the ability of daily oral administration of PEA to achieve long lasting improvements pain and function in patients being treated in a tertiary hospital pain clinic. Patients will be selected based on evidence of neuro- vegetative features as assessed by the Symptom Severity Score (SSS ) from the 2011 revised ACR Fibromyalgia Criteria regardless of primary pain diagnosis. The study aims to have high external validity. Patients will be randomised to PEA or placebo in addition to their current therapy for a period of 6 months. Outcomes will be assessed via the electronic Persistent Pain Outcomes Collaborative (ePPOC) questionnaires, with a primary outcome of Pain Interference as assessed by the Brief Pain Inventory (BPI) at 6 months.