Micronized Palmitoylethanolamide Reduces Temporomandibular Joint Inflammation and Pain

Methods: 15 rats received the injecting of 50 μl of CFA oil/saline(1:1) emulsion into the left TMJ capsule. Control rats received an equal volume of saline. PEA-m® was administered i.p. at dose of 10 mg/kg 30 min before and 6, 24 and 36 hours after CFA injection. Mechanical allodynia was determined with von Frey filaments and oedema by measuring Evans’ blue dye extravasation. Twenty-four and 72 hours after CFA injection, rats were anesthetized and trigeminal ganglion (TG) and brainstem dissected out and processed for immunohistochemistry. The primary antibodies rabbit anti-glial fibrillary acidic protein (GFAP) and rabbit anti-ionized calcium binding adaptor molecule 1 (Iba1) were used as marker for astroglial and microglial cells. All results are expressed as mean±SE of at least three independent experiments. Statistical significance between groups was derived from one-way ANOVA.

Results: CFA-injected animals showed ipsilateral mechanical allodynia and temporomandibular joint edema, accompanied in the TG by a strong increase in the number of GFAP-positive satellite glial cells and by the activation of resident macrophages. Seventy-two hours after CFA injection, activated microglial cells were observed in the ipsilateral trigeminal subnucleus caudalis and in the cervical dorsal horn, with a significant up-regulation of Iba1 immunoreactivity. Repeated PEA administration significantly reduced (p<0.05): (1) the degree of TMJ inflammation and pain; (2) the activated microglial cells; (3) the up-regulation of Iba1.

Conclusions:  The results confirm that PEA reduces pain associated with TMJ inflammation and demonstrate that the effect is mediated by a modulation of glial cells. All together, data suggest that PEA-m® might represent an innovative tool for controlling pain during trigeminal nerve sensitization.