Current evidence shows that tumor necrosis factor alpha (TNF-α) plays an important role in the onset of neuropathic pain. It has been shown that chronic constriction injury (CCI) model induces a bilateral increase of TNF-α expression at the dorsal root ganglion (DRG). Recently it has been determined that the palmitoylethanolamide (PEA) has analgesic effects on animal models of neuropathic pain.
The present study evaluated a potential relation between the analgesic effect of PEA and the changes on TNF-α expression at the DRG in neuropathic pain. CCI induced pain behaviors on ipsilateral paw and a bilateral increase of immunoreactivity (IR) to TNF-α in the L4 and L5 DRG was observed. Administration of PEA (10 mg/kg i.p.), reduced significantly both, thermal hyperalgesia and mechanical allodynia. Thermal threshold values (hyperalgesia) were – 2,96 ± 0,31 s (-7,36 ± 0,12 s control) on day 5 and -1,81 ± 0,30 s (-8,52 ± 0,18 s control) on day 7, while the mechanical threshold (allodynia) values were -1 ranks (-5 ranks control) on day 5 and -0,5 ranks (-6 ranks control) on day 7. In the present study it was also found that the administration of PEA (10 mg / kg, i.p.) reversed the bilateral increase of TNF-α IR in L4 and L5 DRG neurons observed after CCI.
Although these findings give clear evidence about the regulating role of PEA on the expression of TNF-α at the first sensory neuron, the bilateral effects support the hypotheses that the analgesic effect of PEA is not related with the effect on the expression of TNF-α at the DRG.