Background: Although neuropathic pain is a significant problem in polyneuropathy, the underlying molecular mechanisms are poorly understood. The endogenous bioactive lipids 2-arachidonoyl-glycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) are known to influence pain and inflammation in the peripheral nervous system. The aim of this study was to explore the plasma levels of endocannabinoids and related lipids and health-related quality of life in patients with polyneuropathy with and without pain.

Methods: Patients (n = 48) with Chronic Idiopathic Axonal Neuropathy were included. Clinical data were retrieved from medical files. All patients filled out the SF-36 and EQ-5D questionnaires. In addition, blood samples were analyzed for 2-AG, OEA, PEA, and SEA.

Results: Neuropathic pain was reported in 21 of the patients. There were significantly lower levels of 2-AG in patients with neuropathic pain (P = 0.03), but there were no significant differences in OEA (P = 0.61), PEA (P = 0.95), or SEA (P = 0.97) levels. The patients reporting pain in the hands had significantly lower SEA levels, 10.0 versus 15.0 (P = 0.03). The levels of 2-AG were significantly higher among patients reporting paresthesia in their feet (80.1 vs. 56.3; P = 0.02). Levels of PEA, SEA, and 2-AG were decreased in patients with loss of vibration. PEA and SEA were decreased in patients with loss of pain and temperature, and SEA decreased in patients with loss of sense of touch. However, the differences in the levels of bioactive endogenous lipids were not statistically significant when corrected for multiple comparisons.

Conclusion: Alterations of 2-AG levels between polyneuropathy patients with and without neurogenic pain indicate that it could play an essential role. Further studies are warranted.