Unilateral lesion of the nigroestriatal pathway with 6-OHDA induced allodynia and hyperalgesia reverted by pramipexol in rats.

Pain is the non-motor symptom with the highest prevalence in patients with Parkinson's Disease (PD) affecting 40-85%. This study aimed to investigate the development of tactile allodynia and mechanical hyperalgesia after the nigrostriatal dopaminergic lesion induced by the unilateral 6-hydroxydopamine (6-OHDA) injection at different doses in the substantia nigra pars compacta (SNpc). Moreover, we studied the possible antiallodynic and antihyperalgesic effect with the acute and the subacute treatment of the pramipexole (PPX) in rats. First, dopaminergic lesion was realized by the unilateral injection of 6-OHDA (6, 10 and 16 µg/µl) into the SNpc. To know the establishment of motor deficits, we measure several turns and forelimb-use asymmetry by rotational behavior and cylinder, respectively. On the other hand, to investigate allodynia and hyperalgesia induced by 6-OHDA, we used the von Frey filaments. Moreover, antiallodynic and antihyperalgesic effect induced by PPX (0.03, 0.3 and 3 mg/kg, s.c.) was examined on acute and subacute conditions. We found that major dopaminergic lesion with 16 µg/µl of 6-OHDA caused the highest allodynia and hyperalgesia effects in both paws, as well as the major motor deficits. In addition, the treatment with PPX at 0.3 mg/kg reverts the allodynia and the hyperalgesia induced by 6-OHDA. In conclusion, the dopaminergic lesion into SNpc induce allodynia and hyperalgesia in both paws; interestingly the treatment with PPX can be suggested as an analgesic drug for patients with PD.

Structural bases of gastrointestinal motility changes in parkinson's disease: study in rats / Bases estruturais das alterações da motilidade gastrintestinal na doença de parkinson: estudo em ratos

ABSTRACT Background: Gastrointestinal disorders are frequently reported in patients with Parkinson's disease whose disorders reduce the absorption of nutrients and drugs, worsening the clinical condition of patients. However, the mechanisms involved in modifying gastrointestinal pathophysiology have not yet been fully explained. Aim: To evaluate its effects on gastrointestinal motility and the involvement of the vagal and splanchnic pathways. Methods: Male Wistar rats (250-300 g, n = 84) were used and divided into two groups. Group I (6-OHDA) received an intrastriatal injection of 6-hydroxydopamine (21 µg/animal). Group II (control) received a saline solution (NaCl, 0.9%) under the same conditions. The study of gastric emptying, intestinal transit, gastric compliance and operations (vagotomy and splanchnotomy) were performed 14 days after inducing neurodegeneration. Test meal (phenol red 5% glucose) was used to assess the rate of gastric emptying and intestinal transit. Results: Parkinson's disease delayed gastric emptying and intestinal transit at all time periods studied; however, changes in gastric compliance were not observed. The delay in gastric emptying was reversed by pretreatment with vagotomy and splanchnotomy+celiac gangliectomy, thus suggesting the involvement of such pathways in the observed motor disorders. Conclusion: Parkinson's disease compromises gastric emptying, as well as intestinal transit, but does not alter gastric compliance. The delay in gastric emptying was reversed by truncal vagotomy, splanchnotomy and celiac ganglionectomy, suggesting the involvement of such pathways in delaying gastric emptying.

RESUMO Racional: Distúrbios gastrintestinais são frequentemente relatados em pacientes com doença de Parkinson cujos distúrbios reduzem a absorção de nutrientes e fármacos, agravando o quadro clínico dos pacientes. No entanto, os mecanismos envolvidos na alteração da fisiopatologia gastrintestinal ainda não foram totalmente elucidados. Objetivo: Avaliar os seus efeitos sobre a motilidade gastrintestinal e o envolvimento das vias vagal e esplâncnica. Métodos: Ratos Wistar machos (250-300 g, n=84) foram utilizados e divididos em dois grupos. O grupo I (6-OHDA) recebeu injeção intraestriatal de 6-hidroxidopamina (21 µg/animal). O grupo II (controle) recebeu solução salina (NaCl, 0,9%) nas mesmas condições. O estudo do esvaziamento gástrico, trânsito intestinal, complacência gástrica e operações (vagotomia e esplancnotomia) foram realizadas 14 dias após a indução da neurodegeneração. Refeição teste (vermelho de fenol+glicose 5%) foi utilizada para avaliar a taxa de esvaziamento gástrico e o trânsito intestinal. Resultados: A doença de Parkinson retardou o esvaziamento gástrico e o trânsito intestinal em todos os tempos estudados; porém, alterações da complacência gástrica não foram observadas. O retardo do esvaziamento gástrico foi revertido por pré-tratamento com vagotomia e esplancnotomia+gangliectomia celíaca, sugerindo assim, o envolvimento de tais vias nos distúrbios motores observados. Conclusão: A doença de Parkinson compromete o esvaziamento gástrico, bem como o trânsito intestinal, mas não altera a complacência gástrica. O retardo do esvaziamento gástrico foi revertido pela vagotomia troncular, esplancnotomia e gangliectomia celíaca, sugerindo o envolvimento de tais vias no retardo do esvaziamento gástrico.