Abstract
We bilaterally injected 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle of rats and developed bilateral Parkinson’s disease (PD) model rats in order to experimentally investigate the neural mechanisms underlying the alteration of nociception in the orofacial region of patients with PD. We explored the effects of dopamine depletion on nociception by investigating behavioral responses (face rubbing) triggered by subcutaneous administration of formalin into the vibrissa pad. We also assessed the number of c-Fos–immunoreactive (c-Fos-IR) cells in the superficial layers of the trigeminal spinal subnucleus caudalis (Vc). Subcutaneous formalin administration evoked a two-phase increase in face rubbing. We observed the first increase 0–5 min after formalin administration (first phase) and the second increase 10–60 min after administration (second phase). The number of face rubbing behaviors of 6OHDA–injected rats did not significantly change compared with saline–injected rats in both phases. Significant increase of c-Fos-IR cells in the Vc was found in 6-OHDA–injected rats after formalin administration compared with those in saline–injected rats after formalin administration. We also assessed expression of c-Fos-IR cells in the paraventricular nucleus (PVN), and significant decrease of c-Fos-IR cells in the PVN of 6-OHDA–injected rats was found. Taken together, these findings suggest that bilateral dopaminergic denervation evoked by 6-OHDA administration causes hyperalgesia in the trigeminal region and the PVN may be involved in the hyperalgesia.
Highlights
40%–85% of patients with Parkinson’s disease (PD) experience pain [1]
tyrosine hydroxylase (TH)-IR-cells visualized with diaminobenzidine tetrahydrochloride (DAB) and TH-negative cells stained with cresyl violet in the SNpc were found in sham rats and 6-OHDA rats (Fig 1B, S5 and S6 Figs)
The principal finding of this study was the fact that bilateral nigrostriatal lesions induced by 6-OHDA administration into the medial forebrain bundle (MFB) increased c-Fos expression in the Vc following subcutaneous formalin administration into the vibrissa pad
Summary
40%–85% of patients with Parkinson’s disease (PD) experience pain [1]. Previous study has suggested that the dopaminergic system within the basal ganglia plays key roles in handling noxious information [2]. We reported that unilateral PD model rats showed a significant gain in face rubbing and expression levels of c-Fos in the trigeminal spinal subnucleus caudalis (Vc) following subcutaneous administration of formalin into the vibrissa pad [3]. We proposed that unilateral dopamine reduction in the nigrostriatal system evokes hyperalgesia by nociceptive stimulation in the trigeminal region. Several studies have reported responses to noxious stimuli in unilateral PD model rats [4,5,6]; the mechanisms.
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