The effects of palmitoylethanolamide (PEA) on pain and brain activity.

INTERVENTION: Randomized control trial. A total of 60 subjects will be recruited for the study (60 subjects in total comprising 30 subjects in the active treatment and 30 subjects in the placebo group). Participants will be randomly (stratified by age and gender) assigned into either a treatment or placebo group. Treatment group will take 900mg of palmitoylethanolamide (3 x 300mg capsules) orally three times a day with food (morning, noon and night) ‐ total of 2700 mg daily for a total of six weeks. There will be no modifications to the dosage and route of administration during the trial period. To measure patient compliance, at the 6 week follow‐up scan, we will ask each subject to return their pill container. Full compliance will result in an empty bottle. At this point we will be able to ascertain whether there are any remaining pills to determine compliance. If there are any pills remaining we will ask the participant if there are reasons why the full complement of pills were not taken. CONDITION: Persistent orofacial/ trigeminal neuropathic pain PRIMARY OUTCOME: Change in on‐going pain intensity indicated on visual analogue scale. SECONDARY OUTCOME: Beta‐Endorphin measured by collecting 2ml blood via venepuncture. Arterial spin labelling (ASL) scan using MRI: used to measure resting blood flow as a marker of on‐going activity. Brain‐derived neurotrophic factor measured by collecting 2ml blood via venepuncture. Diffusion Tensor Imaging (DTI) scans using MRI: used to explore brain anatomy and in particular astrocyte activation. Psychological measure of depression, anxiety and stress using the Depression Anxiety and Stress Scale (DASS) (Lovibond & Lovibond, 1995) Psychologocal measure of pain catastrophizing using the Pain Catastrophizing Scale (Sullivan et al. 1995) Resting state functional magnetic resonance imaging (fMRI): used to explore resting infra‐slow brain rhythms Substance P measured by collecting 2ml blood via venepuncture. INCLUSION CRITERIA: Subjects with a diagnosis of orofacial / trigeminal neuropathic pain for longer than 3 months duration Aged over 18 years old Willingness to give written informed consent, willingness to complete a magnetic resonance imaging study, complete various questionnaires and to have a blood sample taken