Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: a randomized, double-blind, placebo-controlled trial

Abstract

Neuropathic pain and spasticity after spinal cord injury (SCI) represent significant problems. Palmitoylethanolamide (PEA), a fatty acid amide that is produced in many cells in the body, is thought to potentiate the action of endocannabinoids and to reduce pain and inflammation. This randomized, double-blind, placebo-controlled, parallel multicenter study was performed to investigate the effect of ultramicronized PEA (PEA-um) as add-on therapy on neuropathic pain in individuals with SCI. A pain diary was completed and questionnaires were completed before and after the 12-week treatment with either placebo or PEA-um. The primary outcome measure was the change in mean neuropathic pain intensity from the 1-week baseline period to the last week of treatment measured on a numeric rating scale ranging from 0 to 10. The primary efficacy analysis was the intention to treat (baseline observation carried forward). Secondary outcomes included a per protocol analysis and effects on spasticity, evoked pain, sleep problems, anxiety, depression, and global impression of change. We randomized 73 individuals with neuropathic pain due to SCI, of which 5 had a major protocol violation, and thus 68 were included in the primary analysis. There was no difference in mean pain intensity between PEA-um and placebo treatment (P = 0.46, mean reductions in pain scores 0.4 (−0.1 to 0.9) vs 0.7 (0.2-1.2); difference of means 0.3 (−0.4 to 0.9)). There was also no effect of PEA-um as add-on therapy on spasticity, insomnia, or psychological functioning. PEA was not associated with more adverse effects than placebo.

PPARs and pain

“…In contrast, Andresen and colleagues report that a 12‐week treatment with PEA‐μm did not alleviate pain in patients with spinal cord injury‐induced neuropathic pain, compared to placebo‐treated patients (Andresen et al ., ). The authors however point out that the limited knowledge on PEA‐μm pharmacokinetics, including information on diffusion to the CSF, make it difficult to draw more specific conclusions.…”

The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations

“…Moreover, PEA administration lacked acute and chronic toxicity and was not associated with gastric mucosal lesions (Paladini et al, 2016). In contrast to these promising actions, a more recent report showed that um‐PEA as add‐on therapy was ineffective on neuropathic pain in individuals with SCI (Andresen et al, ). This negative outcome is not surprising considering that the study included patients (i) with different causes and severities of SCI and, more importantly, with an average time since injury of 10 years; (ii) receiving concomitant analgesic medication (dosing and length of treatment not specified); and (iii) with high pain scores at entrance (possibly indicating they were refractory to pain treatment) (Andresen et al, ).…”

N‐Palmitoyl Ethanol Amide Pharmacological Treatment in Patients With Nonsurgical Lumbar Radiculopathy

“…32 A recent meta-analysis evaluating 12 clinical trials showed that PEA induces a time-dependent decrease of pain intensity not related to age or sex. 33 However, Andresen and co-workers, 34 evaluating the role of um-PEA as add-on therapy for neuropathic pain in 68 patients with neuropathic pain due to spinal cord injury, In all patients a significant decrease (P < .001) of values in both VAS and WOMAC scores was obtained after the first cycle (T1) of treatment (um-PEA 1200 mg/d) and was maintained up to the end of the study. T0 indicates admission; T1, 1 month after the beginning of the study; T3, 3 months after the beginning of the study, which represents the end of the study.…”

“…A recent meta‐analysis evaluating 12 clinical trials showed that PEA induces a time‐dependent decrease of pain intensity not related to age or sex . However, Andresen and co‐workers, evaluating the role of um‐PEA as add‐on therapy for neuropathic pain in 68 patients with neuropathic pain due to spinal cord injury, failed to report any difference between um‐PEA and placebo treatment. In agreement with this article, in the present study we failed to demonstrate the effects of 2 months of treatment with um‐PEA on disability in patients with severe pain.…”