ELECTROPHYSIOLOGICAL EVIDENCE ABOUT SEXUAL DIMORPHISM IN THE CLONIDINE-INDUCED INHIBITION OF TRIGEMINAL WIDE DYNAMIC RANGE CELL ACTIVITY

The trigeminal system plays a key role in the pathophysiology of headaches. In this regard, nociceptive experiments in male rodents have shown that at the trigeminal level, clonidine induces antinociception through α_2A- but not α_2B/2C-adrenoceptors. Interestingly, although behavioural experiments suggest that males and females are sensitive to clonidine-induced antinociception, little is known about how neuronal nociceptive processing is affected in females. Therefore, this study was designed to assess the effect of clonidine on trigeminal wide dynamic range (WDR) cell activity in male and female rats. Extracellular unitary recordings of trigeminal WDR cells were performed in anaesthetised Wistar rats and analysed as Aδ-and C-fibres associated discharge. Under these conditions, the effect of local clonidine (3.1–31 nmol) on electrical periorbital-evoked firing of WDR cells was recorded in both sexes. Furthermore, considering that at least three α_2-adrenoceptor subtypes exist (α_2A-, α_2B- and α_2C-adrenoceptors), pharmacological blockade of these receptor subtypes was performed using BRL 44408 (α_2A), imiloxan (α_2B), and JP-1302 (α_2C). Clonidine inhibited the activity of Aδ-and C-fibres in both sexes. This inhibition was observed in 50–60% of cells recorded. Furthermore, the dose necessary to induce similar electrophysiological antinociception was higher in females (31 nmol vs. 10 nmol). In males but not females, clonidine-induced inhibition of Aδ- and C-fibres discharge relies on α_2A-adrenoceptor activation. However, in females, the activation of α_2B/2Cadrenoceptors seems to be relevant to Aδ- but not C-fibre discharge inhibition by clonidine, implying that other mechanisms/receptors may be involved in females.