Title:Palmitoylethanolamide Reduces Formalin-Induced Neuropathic-Like Behaviour Through Spinal Glial/Microglial Phenotypical Changes in Mice
VOLUME: 12 ISSUE: 1
Author(s):Livio Luongo, Francesca Guida, Serena Boccella, Giulia Bellini, Luisa Gatta, Francesca Rossi, Vito de Novellis and Sabatino Maione
Affiliation:Department of Experimental Medicine, Pharmacology Division, The Second University of Naples, via Costantinopoli 16, 80138 Naples, Italy.
Keywords:Palmitoylethanolamide, neuropathic pain, astrocytes, microglia, mouse
Abstract:Palmitoylethanolamide (PEA) is an endogenous cannabinoid-like compound in the central nervous system,
which can modulate several functions in different pathological states, such as inflammation and pain response. We have
here investigated the effect of PEA (5-10 mg/kg, intraperitoneally) on mechanical allodynia and thermal hyperalgesia 3
and 7 days following peripheral injection of formalin. Formalin induced a significant decrease of thermal and mechanical
threshold in the injected and contralateral paw. PEA chronic treatment (once per day) significantly reduced mechanical
allodynia and thermal hyperalgesia in a dose-dependent manner. Consistently, in vivo electrophysiological analysis
revealed a significant increase of the duration and frequency, and a rapid decrease in the onset of evoked activity of the
spinal nociceptive neurons 7 days after formalin. PEA normalized the electrophysiological parameters in a dosedependent
manner. Moreover, we investigated PEA effect on the glial/microglial phenotypical changes associated with
spinal neuronal sensitization. We found that formalin induced a significant microglia and glia activation normalized by
PEA, together with increased expression of glial interleukin 10. Finally, primary microglial cell cultures, conditioned with
PEA or vehicle, where transplanted in naive and formalin-treated mice, and nociceptive neurons were recorded. We
observed that only PEA-conditioned cells normalized the activity of sensitized nociceptive neurons. In conclusion these
data confirm the potent anti-inflammatory and anti-allodynic effect of PEA, and highlight a possible targeted
microglial/glial effect of this drug in the spinal cord.
