From a clinical perspective the most important and promising indications for PEA are linked to neuropathic and chronic pain states, such as diabetic neuropathic pain, sciatic pain, CRPS, pelvic pain and entrapment neuropathic painstates.
In a blind trial, patients affected by pain from synovitis or TMJ osteoarthritis in total were randomly assigned to PEA or ibuprofen groups for two weeks. The decrease in pain reported after two weeks was significantly higher for the PEA-treated group, likewise for improved masticatory function.
In 2012, 20 patients suffering from thalidomide and bortezomib induced neuropathy were reported to have improved nerve functions and less pain after a two-month treatment with PEA. The authors pointed out that although a placebo effect might play a role in the reported pain relief, the changes in neurophysiological measures clearly indicated that PEA exerted a positive action on the myelinated fibre groups.
Sixteen men and fourteen women suffering from two major types of neuropathic pain refractory to analgesic treatment—peripheral diabetic neuropathy (4 men, 7 women) or post-herpetic neuralgia (12 men, 7 women)—whose symptoms spanned eight pain categories ("burning", "osteoarticular", "piercing", etc.) who were under prior treatment with pregabalin were transferred to PEA, after which pregabalin treatment was gradually reintroduced; all were responding well after 45 days, and presented significant decreases in painscores (without drug-drug interactions). 
In 2013, a metareview was published on the clinical efficacy and safety of PEA in the treatment of the common cold and influenza, based on reports from six double-blind, placebo, randomized controlled trials, addressing PEA's proposed anti-inflammatory and retinoprotectant effects.
In 2016, titled: Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efﬁcacy, found 21 clinical studies, of which 16 were clinical trials enrolling a range of 20 to 636 patients and ﬁve were case/pilot studies. In the clinical trials, PEA was used for periods ranging from 14 days to 120 days, and the doses ranged from 300 mg to 1200 mg daily. The authors concluded on the basis of their analyses that PEA was an effective treatment for pain with no registered serious adverse effects.
- Signiﬁcant decrease in post operative pain with PEA treatment.
- Signiﬁcant reduction in pain intensity Total Symptom Score
- Signiﬁcantly larger reduction in pain intensity compared to ibuprofen treatment on day 14
- 600mg better than300mg, both doses signiﬁcantly better than placebo at 21days
- Signiﬁcant reduction of pain intensity with PEA regardless of simultaneous treatment with other drugs compared to placebo at days21