Trigeminal neuroplasticity after pulpitis and oral administration ofparacetamol in rats

Experimental stimulation of dental pulp nociceptors induces plastic changes in the trigeminal subnucleus caudalis (Vc) through increased intracellular calcium levels and discharge of nociceptive afferent fibers. Acetaminophen (paracetamol) is a potent and selective inhibitor of COX-2 within the central nervous system (CNS) and may act in association with the cannabinoid system and the descending serotonergic pathway.

In this context, the main objective of this study is to analyze the plastic changes induced by paracetamol in the nociceptive circuit of the Vc following unilateral dental pulp inflammation (pulpitis) in rats.

Twenty-one female Wistar rats, 50 days old, were divided into three groups. In the experimental group 1 (EG1), a unilateral pulpitis was induced in the left mandibular first molar, and animals received no further treatment. In group 2 (EG2), the procedure was the same as in EG1, but 48 h later, animals received paracetamol in 3 daily doses (300 mg/kg each) every 4 h for 2 days. The control group (CG) received no treatment. After euthanasia, liver, hemimandibles and brainstem samples were analyzed. The results were analyzed using Student's t-test or ANOVA (p<0.05).

5-hydroxytryptamine transporter (5HT-T) analysis in the ipsilateral Vc demonstrated that paracetamol administration increased plexus length and varicosity density compared with EG1 and CG (p<0.05). Paracetamol also increased cannabinoid CB1 receptor (CB1r) expression (p<0.05), and decreased the number of calbindin D28K positive projection neurons (p<0.05).

Following experimental pulpitis, oral administration of paracetamol induces plastic changes in the serotonergic and endocannabinoid systems within the Vc. This plasticity is reflected by a reduced number of fusiform calbindin D28K projection neurons in lamina I, associated with modulation of orofacial nociceptive processing.